The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Stefano Luisi - One of the best experts on this subject based on the ideXlab platform.

  • effects of nomegestrol acetate administration on central and peripheral beta endorphin and Allopregnanolone in ovx rats
    The Journal of Steroid Biochemistry and Molecular Biology, 2008
    Co-Authors: Elena Lenzi, Stefano Luisi, Nicola Pluchino, Silvia Begliuomini, Manolo Centofanti, Letizia Freschi, Elena Casarosa, Filippo Ninni, Valeria Valentino, Michele Luisi
    Abstract:

    Abstract The aim of this study was to investigate the effects of nomegestrol acetate (NOMAc) on the central nervous system by analyzing the neurosteroid Allopregnanolone and the opioid beta-endorphin (β-endorphin). 104 Wistar female rats were used in this study; one group of fertile and one group of ovariectomized rats were used as control. The others were ovariectomized and they underwent a 2-week oral treatment of NOMAc (0.05, 0.1, 0.2, 0.5, 1 mg/kg/day), alone or with 0.05 mg/kg/day of estradiol valerate (E2V). Allopregnanolone and β-endorphin were assessed in different brain areas and in circulation. Ovariectomy decreased Allopregnanolone anywhere except in the adrenal gland and E2V reversed the effects of ovariectomy. 0.5 and 1 mg/kg/day of NOMAc increased Allopregnanolone levels in hippocampus. Combined administration of 1 mg/kg/day of NOMAc plus E2V induced a further increase of Allopregnanolone levels in hippocampus, hypothalamus, and anterior pituitary. NOMAc (1 mg/kg/day) decreased the adrenal content of Allopregnanolone, both by itself and associated with E2V. NOMAc increased hippocampal and hypothalamic content of β-endorphin at the highest doses, and it increased positively E2V action, at 1 mg/kg/day, also in anterior pituitary and plasma. These findings reinforce the clinical data regarding the capability of NOMAc to modulate the pathways involved in mood and behaviour. In fact, due to the NOMAc action on hippocampus, hypothalamus, and anterior pituitary, our results highlight the selectivity of NOMAc on part of the limbic system and the anterior pituitary, regarding both Allopregnanolone and β-endorphin.

  • dydrogesterone increases Allopregnanolone in selected brain areas and in serum of female rats
    Fertility and Sterility, 2008
    Co-Authors: Nicola Pluchino, Stefano Luisi, Silvia Begliuomini, Letizia Freschi, Elena Casarosa, Elena Lenzi, Filippo Ninni, Vito Cela, Andrea R Genazzani
    Abstract:

    Objective To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid Allopregnanolone and the opioid β-endorphin. Design Experimental study on animal model. Setting Academic research environment. Animal(s) 72 Wistar female rats. Intervention(s) One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day). Main Outcome Measure(s) Allopregnanolone and β-endorphin, assessed in different brain areas and in circulation. Result(s) Ovariectomy decreased Allopregnanolone anywhere except in the adrenal gland and reduced β-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased Allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of Allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of β-endorphin induced by E2V. Conclusion(s) Dydrogesterone interacts with Allopregnanolone levels (less with β-endorphin), and it can be considered important modulator of the neuroendocrine function.

  • conjugated equine estrogens reverse the effects of aging on central and peripheral Allopregnanolone and beta endorphin levels in female rats
    Fertility and Sterility, 2004
    Co-Authors: Andrea R Genazzani, Massimo Stomati, Stefano Luisi, F. Bernardi, Elena Casarosa, Marco Palumbo, Simone Puccetti, Alessandro D Genazzani, Michele Luisi
    Abstract:

    Abstract Objective To compare β-endorphin and Allopregnanolone levels and their response to a 2-week oral estrogen treatment with conjugated equine estrogens (CEE) in young ovariectomized (ovx) and in healthy aged female rats. Design Prospective study. Setting Animal laboratory in an academic environment. Animal(s) Twenty-four young ovx and 24 healthy aged female Wistar rats were treated with CEE. Three 8-rat control groups (cycling, ovx, and aged rats) were also included. Intervention(s) Treated rats underwent 14-day oral treatment with three doses of CEE: 0.1 mg/kg/day, 0.5 mg/kg/day, and 2 mg/kg/day. Main outcome measure(s) Cerebral and peripheral β-endorphin and Allopregnanolone levels. Result(s) Beta-endorphin levels were lower in aged vs. cycling and ovx control rats. In brain and serum Allopregnanolone levels were lower in aged vs. cycling control rats, whereas in the adrenals they were higher in aged vs. cycling animals. In the hypothalamus and anterior pituitary Allopregnanolone levels were lower in ovx vs. aged animals. In both ovx and aged animals, CEE treatment reverted the effects of ovariectomy and aging, in a dose-dependent manner. Conclusion(s) Aging is associated with a decrease in cerebral and peripheral β-endorphin and Allopregnanolone. In hypoestrogenic rats, CEE treatment restores Allopregnanolone and β-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.

  • conjugated equine estrogens estrone sulphate and estradiol valerate oral administration in ovariectomized rats effects on central and peripheral Allopregnanolone and β endorphin
    Maturitas, 2002
    Co-Authors: Massimo Stomati, Stefano Luisi, F. Bernardi, Matteo Pieri, Elena Casarosa, Simone Puccetti, Martina Liut, B Quirici, Alessandro D Genazzani, M Luisi
    Abstract:

    Abstract Objectives: Several natural or synthetic estrogenic molecules are commonly used in oral hormone replacement therapy for the relief of menopausal complaints and for the primary prevention of cardiovascular disease and osteoporosis. Little information is available concerning the comparative efficacy of different compounds on neuroendocrine function. The opioid peptide β-endorphin (β-EP), and the neurosteroid Allopregnanolone are considered markers of neuroendocrine function and their synthesis and action is regulated by gonadal steroids. The present study aimed to investigate the effects of a 2-week oral treatment with estradiol valerate (EV), estrone sulphate (ES), or conjugated equine estrogen (CEE) on central and peripheral β-EP and Allopregnanolone levels in ovariectomized (OVX) female rats. Methods: Twelve groups of Wistar OVX rats received oral EV (0.05, 0.1, 0.5 and 1 mg/Kg/day) or ES (0.1, 0.5, 1 and 2 mg/Kg/day), or CEE (0.1, 0.5, 1 and 2 mg/Kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. β-EP content was assessed in hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma, while Allopregnanolone content was assessed in hypothalamus, hippocampus, anterior pituitary, adrenals and serum. Results: Ovariectomy induced a significant decrease in β-EP and Allopregnanolone content in hypothalamus, hippocampus, pituitary, and serum, while it increased Allopregnanolone content in the adrenals. In OVX rats, the administration of each molecule reversed the ovariectomy-induced β-EP and Allopregnanolone changes in a dose-dependent fashion, therefore completely restoring their concentration. At higher doses, the estrogenic compounds induced significantly higher levels of Allopregnanolone and β-EP than in fertile rats. CEE induced higher Allopregnanolone levels in hypothalamus, anterior pituitary and serum than the other estrogenic molecules, and in the hippocampus with respect to EV alone. CEE produced higher β-EP levels in the hippocampus and hypothalamus with respect to EV and ES. Conclusion : In the examined tissue and serum estrogens restore the ovariectomy induced changes in Allopregnanolone and β-EP content in a dose-dependent manner; the magnitude of these effects is not uniform and it is related to the different tissues and the employed compounds.

  • effects of the new generation selective estrogen receptor modulator em 652 and oral administration of estradiol valerate on circulating brain and adrenal β endorphin and Allopregnanolone levels in intact fertile and ovariectomized rats
    Fertility and Sterility, 2002
    Co-Authors: F. Bernardi, Massimo Stomati, Stefano Luisi, Matteo Pieri, Fernand Labrie, Andrea R Genazzani
    Abstract:

    Abstract Objective: To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral β-endorphin (β-EP) and Allopregnanolone levels in fertile and ovariectomized rats. Design: Prospective study. Setting: Animal laboratory in an academic research environment. Animals: Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days. Intervention(s): β-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured. Main Outcome Measure(s): β-Endorphin and Allopregnanolone levels. Result(s): In ovariectomized rats, administration of EV or EM-652 reverses changes in β-EP and Allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in β-EP and Allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum. Conclusions: In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects.

Andrea R Genazzani - One of the best experts on this subject based on the ideXlab platform.

  • correlation between Allopregnanolone levels and depressive symptoms during late menopausal transition and early postmenopause
    Gynecological Endocrinology, 2018
    Co-Authors: Radoslaw Slopien, Nicola Pluchino, Michele Luisi, Alina Warenikszymankiewicz, Stefan Sajdak, Panagiotis Drakopoulos, Andrea R Genazzani
    Abstract:

    AbstractObjectives: This observational, cross-sectional study included 140 women with climacteric symptoms. The aim of the study was to evaluate the correlation between the presence and severity of depressive symptoms and Allopregnanolone levels in women during late menopausal transition and early postmenopause.Methods: The study group was divided into two groups: 45 women in late menopausal transition and 95 early postmenopausal women. We evaluated Kupperman index, Hamilton scale and serum follicle-stimulating hormone, luteinizing hormone, 17β-estradiol, prolactin, total testosterone, dehydroepiandrosterone sulfate and Allopregnanolone levels.Results: We found that serum Allopregnanolone concentration was lower in early postmenopausal women compared to women in late menopausal transition; that there was a correlation between serum Allopregnanolone levels in early postmenopausal women and time since last menstruation, intensity of climacteric symptoms, and intensity of depression symptoms and that there w...

  • dydrogesterone increases Allopregnanolone in selected brain areas and in serum of female rats
    Fertility and Sterility, 2008
    Co-Authors: Nicola Pluchino, Stefano Luisi, Silvia Begliuomini, Letizia Freschi, Elena Casarosa, Elena Lenzi, Filippo Ninni, Vito Cela, Andrea R Genazzani
    Abstract:

    Objective To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid Allopregnanolone and the opioid β-endorphin. Design Experimental study on animal model. Setting Academic research environment. Animal(s) 72 Wistar female rats. Intervention(s) One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day). Main Outcome Measure(s) Allopregnanolone and β-endorphin, assessed in different brain areas and in circulation. Result(s) Ovariectomy decreased Allopregnanolone anywhere except in the adrenal gland and reduced β-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased Allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of Allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of β-endorphin induced by E2V. Conclusion(s) Dydrogesterone interacts with Allopregnanolone levels (less with β-endorphin), and it can be considered important modulator of the neuroendocrine function.

  • drospirenone increases central and peripheral beta endorphin in ovariectomized female rats
    Menopause, 2007
    Co-Authors: Andrea R Genazzani, Nicola Pluchino, Silvia Begliuomini, Matteo Pieri, Manolo Centofanti, Letizia Freschi, Elena Casarosa, Michele Luisi
    Abstract:

    OBJECTIVE: Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid Allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and Allopregnanolone levels in ovariectomized female rats. DESIGN: Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and Allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. RESULTS: Ovariectomy induced a significant decrease in beta-endorphin and Allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased Allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and Allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on Allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or Allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis. CONCLUSIONS: Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with Allopregnanolone production.

  • conjugated equine estrogens reverse the effects of aging on central and peripheral Allopregnanolone and beta endorphin levels in female rats
    Fertility and Sterility, 2004
    Co-Authors: Andrea R Genazzani, Massimo Stomati, Stefano Luisi, F. Bernardi, Elena Casarosa, Marco Palumbo, Simone Puccetti, Alessandro D Genazzani, Michele Luisi
    Abstract:

    Abstract Objective To compare β-endorphin and Allopregnanolone levels and their response to a 2-week oral estrogen treatment with conjugated equine estrogens (CEE) in young ovariectomized (ovx) and in healthy aged female rats. Design Prospective study. Setting Animal laboratory in an academic environment. Animal(s) Twenty-four young ovx and 24 healthy aged female Wistar rats were treated with CEE. Three 8-rat control groups (cycling, ovx, and aged rats) were also included. Intervention(s) Treated rats underwent 14-day oral treatment with three doses of CEE: 0.1 mg/kg/day, 0.5 mg/kg/day, and 2 mg/kg/day. Main outcome measure(s) Cerebral and peripheral β-endorphin and Allopregnanolone levels. Result(s) Beta-endorphin levels were lower in aged vs. cycling and ovx control rats. In brain and serum Allopregnanolone levels were lower in aged vs. cycling control rats, whereas in the adrenals they were higher in aged vs. cycling animals. In the hypothalamus and anterior pituitary Allopregnanolone levels were lower in ovx vs. aged animals. In both ovx and aged animals, CEE treatment reverted the effects of ovariectomy and aging, in a dose-dependent manner. Conclusion(s) Aging is associated with a decrease in cerebral and peripheral β-endorphin and Allopregnanolone. In hypoestrogenic rats, CEE treatment restores Allopregnanolone and β-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.

  • effects of the new generation selective estrogen receptor modulator em 652 and oral administration of estradiol valerate on circulating brain and adrenal β endorphin and Allopregnanolone levels in intact fertile and ovariectomized rats
    Fertility and Sterility, 2002
    Co-Authors: F. Bernardi, Massimo Stomati, Stefano Luisi, Matteo Pieri, Fernand Labrie, Andrea R Genazzani
    Abstract:

    Abstract Objective: To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral β-endorphin (β-EP) and Allopregnanolone levels in fertile and ovariectomized rats. Design: Prospective study. Setting: Animal laboratory in an academic research environment. Animals: Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days. Intervention(s): β-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured. Main Outcome Measure(s): β-Endorphin and Allopregnanolone levels. Result(s): In ovariectomized rats, administration of EV or EM-652 reverses changes in β-EP and Allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in β-EP and Allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum. Conclusions: In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects.

F. Bernardi - One of the best experts on this subject based on the ideXlab platform.

  • conjugated equine estrogens reverse the effects of aging on central and peripheral Allopregnanolone and beta endorphin levels in female rats
    Fertility and Sterility, 2004
    Co-Authors: Andrea R Genazzani, Massimo Stomati, Stefano Luisi, F. Bernardi, Elena Casarosa, Marco Palumbo, Simone Puccetti, Alessandro D Genazzani, Michele Luisi
    Abstract:

    Abstract Objective To compare β-endorphin and Allopregnanolone levels and their response to a 2-week oral estrogen treatment with conjugated equine estrogens (CEE) in young ovariectomized (ovx) and in healthy aged female rats. Design Prospective study. Setting Animal laboratory in an academic environment. Animal(s) Twenty-four young ovx and 24 healthy aged female Wistar rats were treated with CEE. Three 8-rat control groups (cycling, ovx, and aged rats) were also included. Intervention(s) Treated rats underwent 14-day oral treatment with three doses of CEE: 0.1 mg/kg/day, 0.5 mg/kg/day, and 2 mg/kg/day. Main outcome measure(s) Cerebral and peripheral β-endorphin and Allopregnanolone levels. Result(s) Beta-endorphin levels were lower in aged vs. cycling and ovx control rats. In brain and serum Allopregnanolone levels were lower in aged vs. cycling control rats, whereas in the adrenals they were higher in aged vs. cycling animals. In the hypothalamus and anterior pituitary Allopregnanolone levels were lower in ovx vs. aged animals. In both ovx and aged animals, CEE treatment reverted the effects of ovariectomy and aging, in a dose-dependent manner. Conclusion(s) Aging is associated with a decrease in cerebral and peripheral β-endorphin and Allopregnanolone. In hypoestrogenic rats, CEE treatment restores Allopregnanolone and β-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.

  • conjugated equine estrogens estrone sulphate and estradiol valerate oral administration in ovariectomized rats effects on central and peripheral Allopregnanolone and β endorphin
    Maturitas, 2002
    Co-Authors: Massimo Stomati, Stefano Luisi, F. Bernardi, Matteo Pieri, Elena Casarosa, Simone Puccetti, Martina Liut, B Quirici, Alessandro D Genazzani, M Luisi
    Abstract:

    Abstract Objectives: Several natural or synthetic estrogenic molecules are commonly used in oral hormone replacement therapy for the relief of menopausal complaints and for the primary prevention of cardiovascular disease and osteoporosis. Little information is available concerning the comparative efficacy of different compounds on neuroendocrine function. The opioid peptide β-endorphin (β-EP), and the neurosteroid Allopregnanolone are considered markers of neuroendocrine function and their synthesis and action is regulated by gonadal steroids. The present study aimed to investigate the effects of a 2-week oral treatment with estradiol valerate (EV), estrone sulphate (ES), or conjugated equine estrogen (CEE) on central and peripheral β-EP and Allopregnanolone levels in ovariectomized (OVX) female rats. Methods: Twelve groups of Wistar OVX rats received oral EV (0.05, 0.1, 0.5 and 1 mg/Kg/day) or ES (0.1, 0.5, 1 and 2 mg/Kg/day), or CEE (0.1, 0.5, 1 and 2 mg/Kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. β-EP content was assessed in hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma, while Allopregnanolone content was assessed in hypothalamus, hippocampus, anterior pituitary, adrenals and serum. Results: Ovariectomy induced a significant decrease in β-EP and Allopregnanolone content in hypothalamus, hippocampus, pituitary, and serum, while it increased Allopregnanolone content in the adrenals. In OVX rats, the administration of each molecule reversed the ovariectomy-induced β-EP and Allopregnanolone changes in a dose-dependent fashion, therefore completely restoring their concentration. At higher doses, the estrogenic compounds induced significantly higher levels of Allopregnanolone and β-EP than in fertile rats. CEE induced higher Allopregnanolone levels in hypothalamus, anterior pituitary and serum than the other estrogenic molecules, and in the hippocampus with respect to EV alone. CEE produced higher β-EP levels in the hippocampus and hypothalamus with respect to EV and ES. Conclusion : In the examined tissue and serum estrogens restore the ovariectomy induced changes in Allopregnanolone and β-EP content in a dose-dependent manner; the magnitude of these effects is not uniform and it is related to the different tissues and the employed compounds.

  • effects of the new generation selective estrogen receptor modulator em 652 and oral administration of estradiol valerate on circulating brain and adrenal β endorphin and Allopregnanolone levels in intact fertile and ovariectomized rats
    Fertility and Sterility, 2002
    Co-Authors: F. Bernardi, Massimo Stomati, Stefano Luisi, Matteo Pieri, Fernand Labrie, Andrea R Genazzani
    Abstract:

    Abstract Objective: To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral β-endorphin (β-EP) and Allopregnanolone levels in fertile and ovariectomized rats. Design: Prospective study. Setting: Animal laboratory in an academic research environment. Animals: Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days. Intervention(s): β-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured. Main Outcome Measure(s): β-Endorphin and Allopregnanolone levels. Result(s): In ovariectomized rats, administration of EV or EM-652 reverses changes in β-EP and Allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in β-EP and Allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum. Conclusions: In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects.

  • serum Allopregnanolone levels in pregnant women changes during pregnancy at delivery and in hypertensive patients
    The Journal of Clinical Endocrinology and Metabolism, 2000
    Co-Authors: Stefano Luisi, F. Bernardi, Felice Petraglia, Chiara Benedetto, R E Nappi, M Fadalti, Fm Reis, M Luisi, A. R. Genazzani
    Abstract:

    Allopregnanolone is a neuroactive steroid measurable in peripheral circulation. The aim of the present study was to investigate the presence and the possible changes in serum Allopregnanolone and progesterone levels in pregnant women during gestation, at delivery, and in patients with chronic hypertension, with or without superimposed preeclampsia. We also evaluated Allopregnanolone in cord blood. Three groups of pregnant women were studied: 1) healthy controls followed longitudinally throughout gestation (n = 14); 2) at vaginal or cesarean delivery (n = 66); and 3) with chronic hypertension (n = 12), with (n = 7) or without (n = 5) superimposed preeclampsia. Allopregnanolone and progesterone levels were measured in maternal and cord serum by RIA. In healthy pregnant women, serum Allopregnanolone and progesterone levels progressively increased throughout gestation. Whereas no changes were found at vaginal delivery, serum Allopregnanolone and progesterone levels were significantly lower at delivery by emergency cesarean section (P < 0.01). Umbilical cord serum Allopregnanolone and progesterone levels in emergency cesarean were significantly lower than those found at vaginal delivery (P < 0.01). Patients with chronic hypertension, with or without superimposed severe preeclampsia, showed serum Allopregnanolone levels significantly higher than those of healthy women at the same gestational age (P < 0.01). In conclusion, maternal serum Allopregnanolone levels increased during normal gestation were lower in women who underwent emergency cesarean and higher in patients with chronic hypertension, with or without preeclampsia. Because Allopregnanolone is active on the central nervous system and in the control of systemic blood pressure, an involvement of this neurosteroid in the adaptive processes induced by pregnancy is suggested.

  • hypothalamic amenorrhea with normal body weight acth Allopregnanolone and cortisol responses to corticotropin releasing hormone test
    European Journal of Endocrinology, 2000
    Co-Authors: Blazej Meczekalski, Massimo Stomati, A Tonetti, Palmiero Monteleone, Stefano Luisi, F. Bernardi, Matteo Luisi, Felice Petraglia, Andrea R Genazzani
    Abstract:

    Objective: Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic‐pituitary‐adrenal axis in HA. Design: We included 8 patients (aged 23.16 6 1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. Methods: We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, Allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Results: Serum basal levels of FSH, LH, and estradiol as well as basal levels of Allopregnanolone were significantly lower in HA patients than in controls (P < 0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P < 0.001). The response (area under the curve) of ACTH, Allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P < 0.001, P < 0.05, P < 0.05 respectively). Conclusions: In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus‐pituitary‐adrenal axis hyperactivity, are characterized by low Allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, Allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Michael A Rogawski - One of the best experts on this subject based on the ideXlab platform.

  • Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery
    Neurotherapeutics, 2021
    Co-Authors: Dorota Zolkowska, Michael A Rogawski
    Abstract:

    Allopregnanolone, a positive modulator of GABA_A receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of Allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED_50, 5.6 mg/kg), picrotoxin (ED_50, 5.9 mg/kg), and bicuculline seizure tests. The effect peaked at 15 min, decayed over 1 h, and was still evident in some experiments at 6 h. Intranasal Allopregnanolone also delayed the onset of seizures in the maximal PTZ test. At an Allopregnanolone dose (16 mg/kg) that conferred comparable effects on seizure threshold as the benzodiazepines midazolam and diazepam (both at doses of 1 mg/kg), Allopregnanolone caused minimal sedation or motor toxicity in the horizontal screen test whereas both benzodiazepines produced marked behavioral impairment. In addition, intranasal Allopregnanolone failed to cause loss-of-righting reflex in most animals, but when the same dose was administered intramuscularly, all animals became impaired. Intranasal Allopregnanolone (10 mg/kg) caused a rapid increase in brain Allopregnanolone with a T _max of ~5 min after initiation of the intranasal delivery. High levels of Allopregnanolone were recovered in the olfactory bulb ( C _max, 16,000 ng/mg) whereas much lower levels ( C _max, 670 ng/mg) were present in the remainder of the brain. We conclude that the unique ability of intranasal Allopregnanolone to protect against seizures without inducing behavioral adverse effects is due in part to direct nose-to-brain delivery, with preferential transport to brain regions relevant to seizures. Benzodiazepines are commonly administered intranasally for acute seizure therapy, including for the treatment of acute repetitive seizures, but are not transported from nose-to-brain. Intranasal Allopregnanolone acts with greater speed, has less propensity for adverse effects, and has the ability to overcome benzodiazepine refractoriness. This is the first study demonstrating rapid functional central nervous system activity of a nose-to-brain-delivered steroid. Intranasal delivery circumvents the poor oral bioavailability of Allopregnanolone providing a route of administration permitting its evaluation as a treatment for diverse neuropsychiatric indications.

  • Intramuscular Allopregnanolone and ganaxolone in a mouse model of treatment-resistant status epilepticus.
    Epilepsia, 2018
    Co-Authors: Dorota Zolkowska, Michael A Rogawski
    Abstract:

    Allopregnanolone (5α-pregnan-3α-ol-20-one) and its synthetic 3β-methyl analog, ganaxolone, are positive allosteric modulators of synaptic and extrasynaptic γ-aminobutyric acid (GABA)A receptors that exhibit antiseizure activity in diverse animal seizure models, including models of status epilepticus (SE). The 2 neuroactive steroids are being investigated as treatments for SE, including as a treatment for SE induced by chemical threat agents. Intramuscular injection is the preferred route of administration in the prehospital treatment of SE. The objective of this study was to assess the efficacy of intramuscular Allopregnanolone and ganaxolone in the treatment of SE induced by the chemical threat agent tetramethylenedisulfotetramine (TETS). The test agents were administered 40 minutes after the onset of SE when mice are refractory to treatment. Allopregnanolone and ganaxolone (each at 3 mg/kg) terminated SE in, respectively, 92% and 75% of animals, and prevented mortality in 85% and 50% of animals; the mean times to termination of behavioral seizures were, respectively, 172 ± 16 and 447 ± 52 seconds. In a separate series of experiments, mice were dosed with the neuroactive steroids by intramuscular injection, and plasma and brain levels were sampled at various time points following injection to estimate pharmacokinetic parameters. Plasma Cmax (maximum concentration) values for Allopregnanolone and ganaxolone were 645 and 550 ng/mL, respectively. Brain exposure of both steroids was approximately 3-fold the plasma exposure. Two-compartment pharmacokinetic analysis revealed that the central compartment Vd (volume of distribution), CL (clearance), t½ (terminal half-life), and F (intramuscular bioavailability) values for Allopregnanolone and ganaxolone were, respectively, 4.95 L/kg 12.88 L/kg/h,16 minutes, 97%, and 5.07 L/kg, 8.35 L/kg/h, 25 minutes, 95%. Allopregnanolone and ganaxolone are effective in the treatment of TETS-induced SE when administered by the intramuscular route. Allopregnanolone is more rapidly acting and modestly more effective, possibly because it has greater potency on GABAA receptors.

  • Allopregnanolone decreases interictal spiking and fast ripples in an animal model of mesial temporal lobe epilepsy
    Neuropharmacology, 2017
    Co-Authors: Maxime Levesque, Michael A Rogawski, Rochelle Herrington, Leila Leclerc, Massimo Avoli
    Abstract:

    The objective of this study was to characterize the impact of Allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, on interictal spikes and high-frequency oscillations (ripples: 80-200 Hz, fast ripples: 250-500 Hz) in the pilocarpine model of mesial temporal lobe epilepsy. Seven out of 25 Sprague-Dawley rats experiencing 1 h of pilocarpine-induced status epilepticus (SE) began treatment with Allopregnanolone (9.6-12.8 mg/kg/day) on the following day. On day 4 after SE, video-depth EEG recordings from the hippocampal CA3 subfield and the entorhinal cortex were initiated and continued for 12 consecutive days. We found that 66.7% (12/18) of untreated animals exhibited seizures compared to 28.6% (2/7) of Allopregnanolone-treated animals. Interictal spikes occurred less frequently in the CA3 subfield of Allopregnanolone-treated rats (n = 4) than in untreated animals presenting (n = 4) or not presenting (n = 4) with spontaneous seizures (p < 0.05), and were less frequent in the entorhinal cortex compared to both untreated groups (p < 0.05). Finally, Allopregnanolone-treated rats had significantly lower rates of interictal spikes with fast ripples (250-500 Hz) compared to untreated animals but only in CA3 (p < 0.05). Our findings show that Allopregnanolone reduces the frequency of interictal spikes and fast ripples in CA3, a structure that plays an important role in ictogenesis and epileptogenesis. Neurosteroids may therefore influence pathological network activity leading to spontaneous seizures following pilocarpine-induced SE. Recordings after termination of Allopregnanolone treatment will be however required to establish whether Allopregnanolone exerts disease-modifying properties.

  • first in man Allopregnanolone use in super refractory status epilepticus
    Annals of clinical and translational neurology, 2017
    Co-Authors: Michael A Rogawski, Henrikas Vaitkevicius, Aatif M Husain, Eric Rosenthal, Jonathan Rosand, Wendell Bobb, Kiran Reddy, Andrew J Cole
    Abstract:

    Super-refractory status epilepticus (SRSE) is associated with high morbidity and mortality. Treatment of SRSE is complicated by progressive cortical hyperexcitability believed to result in part from synaptic GABA receptor internalization and desensitization. Allopregnanolone, a neurosteroid that positively modulates synaptic and extrasynaptic GABAA receptors, has been proposed as a novel treatment. We describe the first two patients with SRSE who were each successfully treated with a 120-h continuous infusion of Allopregnanolone. Both patients recovered from prolonged SRSE with good cognitive outcomes.

  • combined treatment with diazepam and Allopregnanolone reverses tetramethylenedisulfotetramine tets induced calcium dysregulation in cultured neurons and protects tets intoxicated mice against lethal seizures
    Neuropharmacology, 2015
    Co-Authors: Donald A Bruun, Michael A Rogawski, Zhengyu Cao, Bora Inceoglu, Stephen T Vito, Adam T Austin, Susan Hulsizer, Bruce D Hammock, Daniel J Tancredi, Isaac N Pessah
    Abstract:

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant GABAA receptor blocker. Mice receiving a lethal dose of TETS (0.15 mg/kg i.p.) are rescued from death by a high dose of diazepam (5 mg/kg i.p.) administered shortly after the second clonic seizure (∼20 min post-TETS). However, this high dose of diazepam significantly impairs blood pressure and mobility, and does not prevent TETS-induced neuroinflammation in the brain. We previously demonstrated that TETS alters synchronous Ca(2+) oscillations in primary mouse hippocampal neuronal cell cultures and that pretreatment with the combination of diazepam and Allopregnanolone at concentrations having negligible effects individually prevents TETS effects on intracellular Ca(2+) dynamics. Here, we show that treatment with diazepam and Allopregnanolone (0.1 μM) 20 min after TETS challenge normalizes synchronous Ca(2+) oscillations when added in combination but not when added singly. Similarly, doses (0.03-0.1 mg/kg i.p.) of diazepam and Allopregnanolone that provide minimal protection when administered singly to TETS intoxicated mice increase survival from 10% to 90% when given in combination either 10 min prior to TETS or following the second clonic seizure. This therapeutic combination has negligible effects on blood pressure or mobility. Combined treatment with diazepam and Allopregnanolone also decreases TETS-induced microglial activation. Diazepam and Allopregnanolone have distinct actions as positive allosteric modulators of GABAA receptors that in combination enhance survival and mitigate neuropathology following TETS intoxication without the adverse side effects associated with high dose benzodiazepines. Combination therapy with a benzodiazepine and neurosteroid represents a novel neurotherapeutic strategy with potentially broad application.

Elena Casarosa - One of the best experts on this subject based on the ideXlab platform.

  • effects of nomegestrol acetate administration on central and peripheral beta endorphin and Allopregnanolone in ovx rats
    The Journal of Steroid Biochemistry and Molecular Biology, 2008
    Co-Authors: Elena Lenzi, Stefano Luisi, Nicola Pluchino, Silvia Begliuomini, Manolo Centofanti, Letizia Freschi, Elena Casarosa, Filippo Ninni, Valeria Valentino, Michele Luisi
    Abstract:

    Abstract The aim of this study was to investigate the effects of nomegestrol acetate (NOMAc) on the central nervous system by analyzing the neurosteroid Allopregnanolone and the opioid beta-endorphin (β-endorphin). 104 Wistar female rats were used in this study; one group of fertile and one group of ovariectomized rats were used as control. The others were ovariectomized and they underwent a 2-week oral treatment of NOMAc (0.05, 0.1, 0.2, 0.5, 1 mg/kg/day), alone or with 0.05 mg/kg/day of estradiol valerate (E2V). Allopregnanolone and β-endorphin were assessed in different brain areas and in circulation. Ovariectomy decreased Allopregnanolone anywhere except in the adrenal gland and E2V reversed the effects of ovariectomy. 0.5 and 1 mg/kg/day of NOMAc increased Allopregnanolone levels in hippocampus. Combined administration of 1 mg/kg/day of NOMAc plus E2V induced a further increase of Allopregnanolone levels in hippocampus, hypothalamus, and anterior pituitary. NOMAc (1 mg/kg/day) decreased the adrenal content of Allopregnanolone, both by itself and associated with E2V. NOMAc increased hippocampal and hypothalamic content of β-endorphin at the highest doses, and it increased positively E2V action, at 1 mg/kg/day, also in anterior pituitary and plasma. These findings reinforce the clinical data regarding the capability of NOMAc to modulate the pathways involved in mood and behaviour. In fact, due to the NOMAc action on hippocampus, hypothalamus, and anterior pituitary, our results highlight the selectivity of NOMAc on part of the limbic system and the anterior pituitary, regarding both Allopregnanolone and β-endorphin.

  • dydrogesterone increases Allopregnanolone in selected brain areas and in serum of female rats
    Fertility and Sterility, 2008
    Co-Authors: Nicola Pluchino, Stefano Luisi, Silvia Begliuomini, Letizia Freschi, Elena Casarosa, Elena Lenzi, Filippo Ninni, Vito Cela, Andrea R Genazzani
    Abstract:

    Objective To investigate the effects of dydrogesterone (DYD), a synthetic progestin largely used in hormone therapy, on the central nervous system by studying two markers of the neuroendocrine function: the neurosteroid Allopregnanolone and the opioid β-endorphin. Design Experimental study on animal model. Setting Academic research environment. Animal(s) 72 Wistar female rats. Intervention(s) One group of fertile and one of ovariectomized rats (receiving placebo) were used as control. After ovariectomy, the rats underwent a 2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with estradiol valerate (E2V; 0.05 mg/kg per day). Main Outcome Measure(s) Allopregnanolone and β-endorphin, assessed in different brain areas and in circulation. Result(s) Ovariectomy decreased Allopregnanolone anywhere except in the adrenal gland and reduced β-endorphin central levels; E2V reversed the effects of ovariectomy; and DYD (1 mg/kg per day) increased Allopregnanolone levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of DYD at 1 mg/kg per day plus E2V determined a further increase of Allopregnanolone levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did not modify the levels of β-endorphin induced by E2V. Conclusion(s) Dydrogesterone interacts with Allopregnanolone levels (less with β-endorphin), and it can be considered important modulator of the neuroendocrine function.

  • drospirenone increases central and peripheral beta endorphin in ovariectomized female rats
    Menopause, 2007
    Co-Authors: Andrea R Genazzani, Nicola Pluchino, Silvia Begliuomini, Matteo Pieri, Manolo Centofanti, Letizia Freschi, Elena Casarosa, Michele Luisi
    Abstract:

    OBJECTIVE: Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid Allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and Allopregnanolone levels in ovariectomized female rats. DESIGN: Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and Allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. RESULTS: Ovariectomy induced a significant decrease in beta-endorphin and Allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased Allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and Allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on Allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or Allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis. CONCLUSIONS: Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with Allopregnanolone production.

  • conjugated equine estrogens reverse the effects of aging on central and peripheral Allopregnanolone and beta endorphin levels in female rats
    Fertility and Sterility, 2004
    Co-Authors: Andrea R Genazzani, Massimo Stomati, Stefano Luisi, F. Bernardi, Elena Casarosa, Marco Palumbo, Simone Puccetti, Alessandro D Genazzani, Michele Luisi
    Abstract:

    Abstract Objective To compare β-endorphin and Allopregnanolone levels and their response to a 2-week oral estrogen treatment with conjugated equine estrogens (CEE) in young ovariectomized (ovx) and in healthy aged female rats. Design Prospective study. Setting Animal laboratory in an academic environment. Animal(s) Twenty-four young ovx and 24 healthy aged female Wistar rats were treated with CEE. Three 8-rat control groups (cycling, ovx, and aged rats) were also included. Intervention(s) Treated rats underwent 14-day oral treatment with three doses of CEE: 0.1 mg/kg/day, 0.5 mg/kg/day, and 2 mg/kg/day. Main outcome measure(s) Cerebral and peripheral β-endorphin and Allopregnanolone levels. Result(s) Beta-endorphin levels were lower in aged vs. cycling and ovx control rats. In brain and serum Allopregnanolone levels were lower in aged vs. cycling control rats, whereas in the adrenals they were higher in aged vs. cycling animals. In the hypothalamus and anterior pituitary Allopregnanolone levels were lower in ovx vs. aged animals. In both ovx and aged animals, CEE treatment reverted the effects of ovariectomy and aging, in a dose-dependent manner. Conclusion(s) Aging is associated with a decrease in cerebral and peripheral β-endorphin and Allopregnanolone. In hypoestrogenic rats, CEE treatment restores Allopregnanolone and β-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.

  • conjugated equine estrogens estrone sulphate and estradiol valerate oral administration in ovariectomized rats effects on central and peripheral Allopregnanolone and β endorphin
    Maturitas, 2002
    Co-Authors: Massimo Stomati, Stefano Luisi, F. Bernardi, Matteo Pieri, Elena Casarosa, Simone Puccetti, Martina Liut, B Quirici, Alessandro D Genazzani, M Luisi
    Abstract:

    Abstract Objectives: Several natural or synthetic estrogenic molecules are commonly used in oral hormone replacement therapy for the relief of menopausal complaints and for the primary prevention of cardiovascular disease and osteoporosis. Little information is available concerning the comparative efficacy of different compounds on neuroendocrine function. The opioid peptide β-endorphin (β-EP), and the neurosteroid Allopregnanolone are considered markers of neuroendocrine function and their synthesis and action is regulated by gonadal steroids. The present study aimed to investigate the effects of a 2-week oral treatment with estradiol valerate (EV), estrone sulphate (ES), or conjugated equine estrogen (CEE) on central and peripheral β-EP and Allopregnanolone levels in ovariectomized (OVX) female rats. Methods: Twelve groups of Wistar OVX rats received oral EV (0.05, 0.1, 0.5 and 1 mg/Kg/day) or ES (0.1, 0.5, 1 and 2 mg/Kg/day), or CEE (0.1, 0.5, 1 and 2 mg/Kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. β-EP content was assessed in hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma, while Allopregnanolone content was assessed in hypothalamus, hippocampus, anterior pituitary, adrenals and serum. Results: Ovariectomy induced a significant decrease in β-EP and Allopregnanolone content in hypothalamus, hippocampus, pituitary, and serum, while it increased Allopregnanolone content in the adrenals. In OVX rats, the administration of each molecule reversed the ovariectomy-induced β-EP and Allopregnanolone changes in a dose-dependent fashion, therefore completely restoring their concentration. At higher doses, the estrogenic compounds induced significantly higher levels of Allopregnanolone and β-EP than in fertile rats. CEE induced higher Allopregnanolone levels in hypothalamus, anterior pituitary and serum than the other estrogenic molecules, and in the hippocampus with respect to EV alone. CEE produced higher β-EP levels in the hippocampus and hypothalamus with respect to EV and ES. Conclusion : In the examined tissue and serum estrogens restore the ovariectomy induced changes in Allopregnanolone and β-EP content in a dose-dependent manner; the magnitude of these effects is not uniform and it is related to the different tissues and the employed compounds.