The Experts below are selected from a list of 102 Experts worldwide ranked by ideXlab platform
Petra C Arck - One of the best experts on this subject based on the ideXlab platform.
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Neuroendocrine circuitry and endometriosis: Progesterone Derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro
Journal of Molecular Medicine, 2010Co-Authors: Nadja Tariverdian, Burghard F Klapp, Mirjam Rücke, Julia Szekeres-bartho, Sandra M. Blois, Eva F. Karpf, Peter Sedlmayr, Heribert Kentenich, Friederike Siedentopf, Petra C ArckAbstract:Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited ( n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of Progesterone in serum were determined. Frequency of Progesterone receptor (PR) expression on CD56^+ and CD8^+ peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the Progesterone Derivative dydrogesterone, or both, were evaluated. Furthermore, the production of Progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of Progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56^+PR^+ and CD8^+PR^+ peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of Progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH, increasing upon high psychological stress, might contribute to the peritoneal inflammation present in endometriosis. The therapeutic application of Progesterone Derivatives, CRH blocking agents as well as improvement of stress coping may disrupt the vicious circle between the chronic peritoneal inflammation and high perception of psychological stress in endometriosis.
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the Progesterone Derivative dydrogesterone down regulates neurokinin 1 receptor expression on lymphocytes induces a th2 skew and exerts hypoalgesic effects in mice
Journal of Molecular Medicine, 2006Co-Authors: Arif S Orsal, Sandra M. Blois, Dominika Labuz, Eva M J Peters, Martin Schaefer, Petra C ArckAbstract:Accumulating evidence indicates that the neuropeptide substance P (SP) is predominantly involved in neurogenic inflammation and pain perception via its high-affinity neurokinin 1 receptor (NK-1R). Intriguingly, decreased pain sensitivity is found to be associated with high plasma Progesterone levels. We hypothesize that Progesterone may attenuate nociception and associated inflammatory response via NK-1R-dependent pathways. To address our hypothesis, we incubated splenic lymphocytes from CBA/J female mice with different concentrations of the Progesterone Derivative dydrogesterone. Subsequently, the expressions of NK-1R and T helper (Th1)-type cytokines were analyzed by flow cytometry. Next, we subcutaneously injected CBA/J mice with 1.25 mg of dydrogesterone in 200-μl sesame oil; control mice were sham-injected. Tail flick test to detect the nociceptive threshold was performed in 30-min intervals upon injection. Lymphocytes were isolated from blood and uterus and analyzed for NK-1R surface expression. Immunohistochemical analyses were performed to investigate the uterine tissue distribution of NK-1R. Dydrogesterone induced a decrease in the percentage of NK-1R+ lymphocytes in vitro and in vivo. Additionally, an increase in Th2-type and a decrease in Th1-type cytokines could be detected in vitro after incubation with dydrogesterone. An increased tail flick latency following dydrogesterone injection supported the concept that decreased expression of the NK-1R on lymphocytes is associated with an increased pain threshold. Taken together, these results clearly reveal a pathway by which dydrogesterone or Progesterone respectively modulates the cross talk of the nervous, endocrine and immune systems in inflammation and pain.
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the Progesterone Derivative dydrogesterone abrogates murine stress triggered abortion by inducing a th2 biased local immune response
Steroids, 2003Co-Authors: Ricarda Joachim, Ana Claudia Zenclussen, Beata Polgar, Alison J Douglas, Stefan Fest, Maike Knackstedt, Burghard F Klapp, Petra C ArckAbstract:Stress is known to induce abortions in mice and humans, putatively via increased levels of abortogenic Th1 cytokines and a decrease of Progesterone. Adequate levels of Progesterone exert an antiabortive response through binding to the Progesterone-receptor, which induces the release of Progesterone-induced blocking factor (PIBF) from lymphocytes. PIBF is highly pregnancy-protective by induction of a Th2 biased immune activity. The aim of this study was to investigate the effect of the Progesterone Derivative dydrogesterone (6-dehydro-retroProgesterone) in stress-triggered murine abortion. DBA/2J-mated CBA/J female mice were randomized in different groups: two groups were treated with different dydrogesterone dosages in a single injection before exposure to sound stress on Day 5 of pregnancy, one group was exposed to stress without dydrogesterone treatment, the fourth group received no stress and no dydrogesterone. On gestation Day 13, a highly elevated abortion rate was detected in stressed mice compared to control mice. Stressed animals presented lower levels of Progesterone and PIBF in plasma and a reduced staining intensity of Progesterone receptor at the feto-maternal interface. Injection of dydrogesterone abrogated the effect of stress on the abortion rate. Further, dydrogesterone increased levels of plasma PIBF in stressed mice, but did not affect Progesterone levels. Interestingly, dydrogesterone dramatically increased the percentage of IL-4 positive decidual immune cells in stressed mice. Our data suggest that dydrogesterone abrogates stress-triggered abortion by inducing a Th2 biased local immune response.
Allan E Herbison - One of the best experts on this subject based on the ideXlab platform.
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direct regulation of postnatal gnrh neurons by the Progesterone Derivative allopregnanolone in the mouse
Endocrinology, 2001Co-Authors: Michael J Skynner, Allan E HerbisonAbstract:The mechanisms through which gonadal steroids exert critical feedback actions upon the activity of the GnRH neurons are not understood. We have examined here whether Progesterone may modulate the electrical activity of the GnRH neurons following its rapid metabolism to the neuroactive steroid allopregnanolone within the brain. Using an acute brain slice preparation, whole-cell, patch-clamp recordings were made from GnRH neurons of juvenile (postnatal d 15–20) and adult (postnatal d 60–70) female mice in the presence of tetrodotoxin. Progesterone (1 μm) was not observed to have any actions (up to 5 min exposure) upon GnRH neurons. However, allopregnanolone (500 nm-1 μm) exerted rapid (<1 min) effects upon the baseline membrane potential of all GnRH neurons and also significantly (P < 0.01) enhanced their GABA responses by up to 4-fold. All GABA and allopregnanolone responses were abolished by the GABAA receptor antagonist bicuculline. No differences were detected in the allopregnanolone sensitivity of GnRH...
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Direct regulation of postnatal GnRH neurons by the Progesterone Derivative allopregnanolone in the mouse.
Endocrinology, 2001Co-Authors: Michael J Skynner, Allan E HerbisonAbstract:The mechanisms through which gonadal steroids exert critical feedback actions upon the activity of the GnRH neurons are not understood. We have examined here whether Progesterone may modulate the electrical activity of the GnRH neurons following its rapid metabolism to the neuroactive steroid allopregnanolone within the brain. Using an acute brain slice preparation, whole-cell, patch-clamp recordings were made from GnRH neurons of juvenile (postnatal d 15–20) and adult (postnatal d 60–70) female mice in the presence of tetrodotoxin. Progesterone (1 μm) was not observed to have any actions (up to 5 min exposure) upon GnRH neurons. However, allopregnanolone (500 nm-1 μm) exerted rapid (
Michael J Skynner - One of the best experts on this subject based on the ideXlab platform.
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direct regulation of postnatal gnrh neurons by the Progesterone Derivative allopregnanolone in the mouse
Endocrinology, 2001Co-Authors: Michael J Skynner, Allan E HerbisonAbstract:The mechanisms through which gonadal steroids exert critical feedback actions upon the activity of the GnRH neurons are not understood. We have examined here whether Progesterone may modulate the electrical activity of the GnRH neurons following its rapid metabolism to the neuroactive steroid allopregnanolone within the brain. Using an acute brain slice preparation, whole-cell, patch-clamp recordings were made from GnRH neurons of juvenile (postnatal d 15–20) and adult (postnatal d 60–70) female mice in the presence of tetrodotoxin. Progesterone (1 μm) was not observed to have any actions (up to 5 min exposure) upon GnRH neurons. However, allopregnanolone (500 nm-1 μm) exerted rapid (<1 min) effects upon the baseline membrane potential of all GnRH neurons and also significantly (P < 0.01) enhanced their GABA responses by up to 4-fold. All GABA and allopregnanolone responses were abolished by the GABAA receptor antagonist bicuculline. No differences were detected in the allopregnanolone sensitivity of GnRH...
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Direct regulation of postnatal GnRH neurons by the Progesterone Derivative allopregnanolone in the mouse.
Endocrinology, 2001Co-Authors: Michael J Skynner, Allan E HerbisonAbstract:The mechanisms through which gonadal steroids exert critical feedback actions upon the activity of the GnRH neurons are not understood. We have examined here whether Progesterone may modulate the electrical activity of the GnRH neurons following its rapid metabolism to the neuroactive steroid allopregnanolone within the brain. Using an acute brain slice preparation, whole-cell, patch-clamp recordings were made from GnRH neurons of juvenile (postnatal d 15–20) and adult (postnatal d 60–70) female mice in the presence of tetrodotoxin. Progesterone (1 μm) was not observed to have any actions (up to 5 min exposure) upon GnRH neurons. However, allopregnanolone (500 nm-1 μm) exerted rapid (
Gilbert Schaison - One of the best experts on this subject based on the ideXlab platform.
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the antigonadotropic activity of a 19 nor Progesterone Derivative is exerted both at the hypothalamic and pituitary levels in women
The Journal of Clinical Endocrinology and Metabolism, 1999Co-Authors: Beatrice Couzinet, Jacques Young, Michele Kujas, Gery Meduri, Sylvie Brailly, Jean Louis Thomas, Philippe Chanson, Gilbert SchaisonAbstract:We have previously shown in postmenopausal women that a 19-nor-Progesterone Derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor. The aim of the present study was to further assess the action of this progestin on gonadotropin secretion in women. To demonstrate at which level of the hypothalamo-pituitary-ovarian axis the gonadotropin inhibition was exerted, 10 normally cycling (NC) women, 3 women with a gonadotropin-independent ovarian function[ McCune-Albright (MCA) syndrome], and 5 women with functional hypothalamic amenorrhea (FHA) participated in the study. NC women were treated orally with 5 mg NOMA for 21 days, after one control cycle. Plasma estradiol (E2) and Progesterone, LH, and FSH levels were measured during each cycle. A frequent sampling study (every 10 min for 4 h), followed by a classic GnRH test (100 μg, iv), was performed on day 11. Women with MCA were studied before, during NOMA, and after long-actin...
T Wolff - One of the best experts on this subject based on the ideXlab platform.
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the liver as origin and target of reactive intermediates exemplified by the Progesterone Derivative cyproterone acetate
Advances in Experimental Medicine and Biology, 1996Co-Authors: L R Schwarz, S Werner, Jan Topinka, U Andrae, I Neumann, T WolffAbstract:Since the middle of the last century it is known that chemicals can cause liver injury (cf. Zimmerman, 1978). In 1860, a severe fatty liver in man was ascribed to phosphorous intoxication. During the first half of the 20th century several hepatotoxins have been extensively studied and in the second half of this century it became clear that in many cases enzymatically ‘activated’ metabolites of xenobiotics are responsible for the toxic effects observed (cf. Zimmerman, 1978; Hinson et al., 1994). The liver was found to express the highest concentrations and greatest variety of xenobiotic metabolizing enzymes in the body (cf. Zimmerman, 1978; Watkins, 1990). This high metabolic capacity turned out to be a primary cause of the liver specificity of toxic xenobiotics. Chemically induced liver damage may have three main manifestations (Fig. 1).