The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
Pamela L Mellon - One of the best experts on this subject based on the ideXlab platform.
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synergistic induction of follicle stimulating Hormone β subunit gene expression by Gonadal Steroid Hormone receptors and smad proteins
Endocrinology, 2008Co-Authors: Varykina G Thackray, Pamela L MellonAbstract:LH and FSH play crucial roles in mammalian reproduction by mediating Steroidogenesis and gametogenesis. Gonadal Steroid Hormones influence gonadotropin production via feedback to the hypothalamus and pituitary. We previously demonstrated that progesterone and testosterone can stimulate expression of the FSH β-subunit gene in immortalized gonadotrope-derived LβT2 cells. Herein, we investigate how these Gonadal Steroids modulate activin signaling in the gonadotrope. Cotreatment of LβT2 cells or mouse primary pituitary cells with Steroids and activin results in a synergistic induction of FSHβ gene expression. This synergy decreases when DNA-binding mutations are introduced into the Steroid receptors or when mutations that reduce Steroid Hormone responsiveness are introduced into the FSHβ promoter, indicating that synergy requires direct DNA binding of the Steroid receptors. Furthermore, classical activin signaling via Smad proteins is necessary for this synergy. In addition, these Steroid receptors physically interact with Smads and are sufficient for the synergism to occur on the FSHβ promoter. Disruption of Smad binding to the promoter with a Smad protein lacking the DNA-binding domain or an FSHβ promoter containing mutated activin-response elements prevents the synergistic enhancement of FSHβ transcription. Collectively, our data demonstrate that the molecular mechanism for Gonadal Steroid Hormone action on the FSHβ promoter involves cross-talk between the Steroid and activin signaling pathways. They also reveal that this synergism requires binding of both the Steroid receptors and Smad proteins to their cognate DNA-binding elements and likely involves a direct protein-protein interaction between the two types of transcription factors.
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Synergistic Induction of Follicle-Stimulating Hormone β-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smad Proteins
Endocrinology, 2007Co-Authors: Varykina G Thackray, Pamela L MellonAbstract:LH and FSH play crucial roles in mammalian reproduction by mediating Steroidogenesis and gametogenesis. Gonadal Steroid Hormones influence gonadotropin production via feedback to the hypothalamus and pituitary. We previously demonstrated that progesterone and testosterone can stimulate expression of the FSH beta-subunit gene in immortalized gonadotrope-derived LbetaT2 cells. Herein, we investigate how these Gonadal Steroids modulate activin signaling in the gonadotrope. Cotreatment of LbetaT2 cells or mouse primary pituitary cells with Steroids and activin results in a synergistic induction of FSHbeta gene expression. This synergy decreases when DNA-binding mutations are introduced into the Steroid receptors or when mutations that reduce Steroid Hormone responsiveness are introduced into the FSHbeta promoter, indicating that synergy requires direct DNA binding of the Steroid receptors. Furthermore, classical activin signaling via Smad proteins is necessary for this synergy. In addition, these Steroid receptors physically interact with Smads and are sufficient for the synergism to occur on the FSHbeta promoter. Disruption of Smad binding to the promoter with a Smad protein lacking the DNA-binding domain or an FSHbeta promoter containing mutated activin-response elements prevents the synergistic enhancement of FSHbeta transcription. Collectively, our data demonstrate that the molecular mechanism for Gonadal Steroid Hormone action on the FSHbeta promoter involves cross-talk between the Steroid and activin signaling pathways. They also reveal that this synergism requires binding of both the Steroid receptors and Smad proteins to their cognate DNA-binding elements and likely involves a direct protein-protein interaction between the two types of transcription factors.
Ronald P. Hammer - One of the best experts on this subject based on the ideXlab platform.
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Gonadal Steroid Hormone regulation of proopiomelanocortin gene expression in neurons that innervate the median eminence of the rat
Neuroscience letters, 1997Co-Authors: Sun Cheung, Ronald P. HammerAbstract:The effect of Gonadal Steroid Hormones on the expression of proopiomelanocortin (POMC) in neurons that innervate the median eminence (ME) was investigated using combined retrograde neuronal labeling and in situ hybridization histochemistry. It was observed that Gonadal Hormone treatment significantly increased the expression of POMC mRNA. The results suggest that POMC neurons directly innervate the ME, where POMC-derived peptides could rapidly inhibit luteinizing Hormone-releasing Hormone release following the preovulatory Hormone surge.
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Gonadal Steroid Hormone dependence of β endorphin like immunoreactivity in the medial preoptic area of the rat
Brain Research, 1995Co-Authors: Sun Cheung, Joy Salinas, Ronald P. HammerAbstract:: Gonadal Steroid Hormones are known to alter the expression of proopiomelanocortin (POMC) mRNA in neurons of the arcuate nucleus (ARC). These neurons send projections to the medial preoptic area (MPOA), wherein mu-opiate receptor density is cyclical and Gonadal Steroid Hormone-dependent. Although beta-endorphin-(beta-Endo) content in the MPOA is known to vary across the estrous cycle, the effect of Gonadal Hormones on the distribution and density of beta-Endo-like immunoreactive (IR) fiber density in the preoptic area is unknown. In the present study, immunohistochemical staining was used to investigate the effects of Gonadal Steroid Hormone treatment on beta-Endo-like IR fibers in the MPOA of ovariectomized (OVX) female rats. The density of beta-Endo-like IR fibers was low in the MPOA of OVX rats, but increased slightly following treatment with 17 beta-estradiol (E2) or 3 h after subsequent progesterone (P) injection. However, beta-Endo-like IR fiber density increased significantly 27 h after E2P treatment, and remained elevated 51 h after E2P treatment in the periventricular zone and in the medial portion of the medial preoptic nucleus, although the general distribution of fibers was unchanged. These results suggest that the density of MPOA beta-Endo innervation is normally Gonadal Steroid Hormone-dependent and that the medial MPOA contains greater opioid tone than the lateral MPOA regardless of the hormonal state. Furthermore, since beta-Endo-like IR fiber density remained elevated even though Gonadal Hormone levels decreased, additional factors might modulate the release or turnover of beta-Endo in the MPOA during normal estrous cycling.
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Gonadal Steroid Hormone-dependence of beta-endorphin-like immunoreactivity in the medial preoptic area of the rat.
Brain research, 1995Co-Authors: Sun Cheung, Joy Salinas, Ronald P. HammerAbstract:Gonadal Steroid Hormones are known to alter the expression of proopiomelanocortin (POMC) mRNA in neurons of the arcuate nucleus (ARC). These neurons send projections to the medial preoptic area (MPOA), wherein mu-opiate receptor density is cyclical and Gonadal Steroid Hormone-dependent. Although beta-endorphin-(beta-Endo) content in the MPOA is known to vary across the estrous cycle, the effect of Gonadal Hormones on the distribution and density of beta-Endo-like immunoreactive (IR) fiber density in the preoptic area is unknown. In the present study, immunohistochemical staining was used to investigate the effects of Gonadal Steroid Hormone treatment on beta-Endo-like IR fibers in the MPOA of ovariectomized (OVX) female rats. The density of beta-Endo-like IR fibers was low in the MPOA of OVX rats, but increased slightly following treatment with 17 beta-estradiol (E2) or 3 h after subsequent progesterone (P) injection. However, beta-Endo-like IR fiber density increased significantly 27 h after E2P treatment, and remained elevated 51 h after E2P treatment in the periventricular zone and in the medial portion of the medial preoptic nucleus, although the general distribution of fibers was unchanged. These results suggest that the density of MPOA beta-Endo innervation is normally Gonadal Steroid Hormone-dependent and that the medial MPOA contains greater opioid tone than the lateral MPOA regardless of the hormonal state. Furthermore, since beta-Endo-like IR fiber density remained elevated even though Gonadal Hormone levels decreased, additional factors might modulate the release or turnover of beta-Endo in the MPOA during normal estrous cycling.
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Gonadal Steroid Hormone REGULATION OF PROOPIOMELANOCORTIN GENE EXPRESSION IN ARCUATE NEURONS THAT INNERVATE THE MEDIAL PREOPTIC AREA OF THE RAT
Neuroendocrinology, 1995Co-Authors: Sun Cheung, Ronald P. HammerAbstract:The density of beta-endorphin (beta-endo)-like immunoreactive (IR) fibers in the medial preoptic area (MPOA) has been shown to vary across the estrous cycle and is Gonadal Steroid Hormone-dependent. These beta-endo-containing fibers are presumably projections of proopiomelanocortin (POMC) neurons which are located in the arcuate nucleus (ARC). POMC mRNA level varies across the estrous cycle in the ARC and its expression is differentially altered by Gonadal Steroid Hormones. However, it is unclear how Gonadal Steroids regulate POMC gene expression in ARC neurons that innervate the MPOA. Therefore, combined fluorogold (FG) retrograde neuronal labeling and in situ hybridization histochemistry were used to investigate the effects of Gonadal Steroid Hormone treatment on POMC gene expression in ARC neurons supplying the MPOA of ovariectomized (OVX) female rats. POMC-expressing cells were located in the ARC and median eminence (ME), wherein such neurons were significantly larger than unlabeled cells that surround them. A relatively greater number of ARC POMC neurons were observed to innervate the medial portion of the medial preoptic nucleus (MPN) than the lateral portion of the MPN. Estradiol (E2) and progesterone (P) treatment before FG injection did not affect the number of FG and POMC double-labeled neurons in the ARC, which suggests that Hormone treatment did not alter the number of POMC-expressing neurons projecting to the MPN. In OVX animals, ARC POMC mRNA labeling was relatively low, and increased significantly in neurons of the most rostral ARC region 48 h after E2 treatment. P administration enhanced and prolonged the effect of E2 in this group of ARC neurons. E2P treatment significantly increased POMC mRNA expression beginning 13 h after P injection in all but the most caudal ARC POMC neurons. Thereafter, E2P treatment gradually increased POMC mRNA expression for at least 1 additional day. Gonadal Steroid Hormone treatment apparently affects POMC mRNA expression uniformly in neurons of the same ARC subdivision without regard to their efferent targets. Diurnal variation of POMC mRNA expression is present only in the most rostral ARC region, which contains a population of E2-sensitive POMC neurons. The results suggest that the relatively greater beta-endo-like IR fiber density in the medial MPN is due to a greater number of POMC neurons innervating this region. The pattern of innervation of the MPN by POMC neurons is unaffected by Gonadal Steroid Hormone treatment, which appears to induce POMC expression in ARC neurons, and eventually to stimulate the synthesis and transport of beta-endo in POMC neuronal axons which project to the MPOA.(ABSTRACT TRUNCATED AT 400 WORDS)
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Gonadal Steroid Hormones and hypothalamic opioid circuitry
Hormones and behavior, 1994Co-Authors: Ronald P. Hammer, Lei Zhou, Sun CheungAbstract:Abstract Endogenous opioid peptides derived from several gene families are localized within hypothalamic regions known to be involved in the regulation of reproduction. For example, the proenkephalin gene products, met- and leu-enkephalin, and the proopiomelanocortin (POMC) gene product, β-endorphin, are found in the rat medial preoptic area (MPOA). Moreover, the expression of these peptides and their receptors varies across the estrous cycle in the female rat. We have examined the Gonadal Steroid regulation of μ-opiate receptors and opioid peptides in the MPOA, and POMC mRNA expression in neurons that innervate the MPOA. μ-Opiate receptors in the MPOA are sexually dimorphic and Gonadal Steroid Hormone-dependent. Hormonal priming of ovariectomized rats with estrogen and progesterone (P) upregulates MPOA μ-receptors 27, but not 3, hr after P treatment. Inhibition of protein synthesis during the first 6 hr after P prevents receptor upregulation, The density of β-endorphin fibers in the MPOA also increases following Hormone treatment, and POMC mRNA expression in neurons that innervate the MPOA is induced by Hormone treatment beginning 13 hr after P treatment. This delayed response might be ubiquitous among POMC neurons, as those innervating the median eminence also exhibit increased POMC mRNA expression along a similar time course. The results suggest that hormonal feedback regulates opioid peptides which act at μ-receptors in the MPOA to influence reproductive behavior and cyclicity. These opioid functions represent an important component in the complex regulatory processes which control reproduction.
Varykina G Thackray - One of the best experts on this subject based on the ideXlab platform.
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synergistic induction of follicle stimulating Hormone β subunit gene expression by Gonadal Steroid Hormone receptors and smad proteins
Endocrinology, 2008Co-Authors: Varykina G Thackray, Pamela L MellonAbstract:LH and FSH play crucial roles in mammalian reproduction by mediating Steroidogenesis and gametogenesis. Gonadal Steroid Hormones influence gonadotropin production via feedback to the hypothalamus and pituitary. We previously demonstrated that progesterone and testosterone can stimulate expression of the FSH β-subunit gene in immortalized gonadotrope-derived LβT2 cells. Herein, we investigate how these Gonadal Steroids modulate activin signaling in the gonadotrope. Cotreatment of LβT2 cells or mouse primary pituitary cells with Steroids and activin results in a synergistic induction of FSHβ gene expression. This synergy decreases when DNA-binding mutations are introduced into the Steroid receptors or when mutations that reduce Steroid Hormone responsiveness are introduced into the FSHβ promoter, indicating that synergy requires direct DNA binding of the Steroid receptors. Furthermore, classical activin signaling via Smad proteins is necessary for this synergy. In addition, these Steroid receptors physically interact with Smads and are sufficient for the synergism to occur on the FSHβ promoter. Disruption of Smad binding to the promoter with a Smad protein lacking the DNA-binding domain or an FSHβ promoter containing mutated activin-response elements prevents the synergistic enhancement of FSHβ transcription. Collectively, our data demonstrate that the molecular mechanism for Gonadal Steroid Hormone action on the FSHβ promoter involves cross-talk between the Steroid and activin signaling pathways. They also reveal that this synergism requires binding of both the Steroid receptors and Smad proteins to their cognate DNA-binding elements and likely involves a direct protein-protein interaction between the two types of transcription factors.
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Synergistic Induction of Follicle-Stimulating Hormone β-Subunit Gene Expression by Gonadal Steroid Hormone Receptors and Smad Proteins
Endocrinology, 2007Co-Authors: Varykina G Thackray, Pamela L MellonAbstract:LH and FSH play crucial roles in mammalian reproduction by mediating Steroidogenesis and gametogenesis. Gonadal Steroid Hormones influence gonadotropin production via feedback to the hypothalamus and pituitary. We previously demonstrated that progesterone and testosterone can stimulate expression of the FSH beta-subunit gene in immortalized gonadotrope-derived LbetaT2 cells. Herein, we investigate how these Gonadal Steroids modulate activin signaling in the gonadotrope. Cotreatment of LbetaT2 cells or mouse primary pituitary cells with Steroids and activin results in a synergistic induction of FSHbeta gene expression. This synergy decreases when DNA-binding mutations are introduced into the Steroid receptors or when mutations that reduce Steroid Hormone responsiveness are introduced into the FSHbeta promoter, indicating that synergy requires direct DNA binding of the Steroid receptors. Furthermore, classical activin signaling via Smad proteins is necessary for this synergy. In addition, these Steroid receptors physically interact with Smads and are sufficient for the synergism to occur on the FSHbeta promoter. Disruption of Smad binding to the promoter with a Smad protein lacking the DNA-binding domain or an FSHbeta promoter containing mutated activin-response elements prevents the synergistic enhancement of FSHbeta transcription. Collectively, our data demonstrate that the molecular mechanism for Gonadal Steroid Hormone action on the FSHbeta promoter involves cross-talk between the Steroid and activin signaling pathways. They also reveal that this synergism requires binding of both the Steroid receptors and Smad proteins to their cognate DNA-binding elements and likely involves a direct protein-protein interaction between the two types of transcription factors.
Sun Cheung - One of the best experts on this subject based on the ideXlab platform.
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Gonadal Steroid Hormone regulation of proopiomelanocortin gene expression in neurons that innervate the median eminence of the rat
Neuroscience letters, 1997Co-Authors: Sun Cheung, Ronald P. HammerAbstract:The effect of Gonadal Steroid Hormones on the expression of proopiomelanocortin (POMC) in neurons that innervate the median eminence (ME) was investigated using combined retrograde neuronal labeling and in situ hybridization histochemistry. It was observed that Gonadal Hormone treatment significantly increased the expression of POMC mRNA. The results suggest that POMC neurons directly innervate the ME, where POMC-derived peptides could rapidly inhibit luteinizing Hormone-releasing Hormone release following the preovulatory Hormone surge.
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Gonadal Steroid Hormone dependence of β endorphin like immunoreactivity in the medial preoptic area of the rat
Brain Research, 1995Co-Authors: Sun Cheung, Joy Salinas, Ronald P. HammerAbstract:: Gonadal Steroid Hormones are known to alter the expression of proopiomelanocortin (POMC) mRNA in neurons of the arcuate nucleus (ARC). These neurons send projections to the medial preoptic area (MPOA), wherein mu-opiate receptor density is cyclical and Gonadal Steroid Hormone-dependent. Although beta-endorphin-(beta-Endo) content in the MPOA is known to vary across the estrous cycle, the effect of Gonadal Hormones on the distribution and density of beta-Endo-like immunoreactive (IR) fiber density in the preoptic area is unknown. In the present study, immunohistochemical staining was used to investigate the effects of Gonadal Steroid Hormone treatment on beta-Endo-like IR fibers in the MPOA of ovariectomized (OVX) female rats. The density of beta-Endo-like IR fibers was low in the MPOA of OVX rats, but increased slightly following treatment with 17 beta-estradiol (E2) or 3 h after subsequent progesterone (P) injection. However, beta-Endo-like IR fiber density increased significantly 27 h after E2P treatment, and remained elevated 51 h after E2P treatment in the periventricular zone and in the medial portion of the medial preoptic nucleus, although the general distribution of fibers was unchanged. These results suggest that the density of MPOA beta-Endo innervation is normally Gonadal Steroid Hormone-dependent and that the medial MPOA contains greater opioid tone than the lateral MPOA regardless of the hormonal state. Furthermore, since beta-Endo-like IR fiber density remained elevated even though Gonadal Hormone levels decreased, additional factors might modulate the release or turnover of beta-Endo in the MPOA during normal estrous cycling.
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Gonadal Steroid Hormone-dependence of beta-endorphin-like immunoreactivity in the medial preoptic area of the rat.
Brain research, 1995Co-Authors: Sun Cheung, Joy Salinas, Ronald P. HammerAbstract:Gonadal Steroid Hormones are known to alter the expression of proopiomelanocortin (POMC) mRNA in neurons of the arcuate nucleus (ARC). These neurons send projections to the medial preoptic area (MPOA), wherein mu-opiate receptor density is cyclical and Gonadal Steroid Hormone-dependent. Although beta-endorphin-(beta-Endo) content in the MPOA is known to vary across the estrous cycle, the effect of Gonadal Hormones on the distribution and density of beta-Endo-like immunoreactive (IR) fiber density in the preoptic area is unknown. In the present study, immunohistochemical staining was used to investigate the effects of Gonadal Steroid Hormone treatment on beta-Endo-like IR fibers in the MPOA of ovariectomized (OVX) female rats. The density of beta-Endo-like IR fibers was low in the MPOA of OVX rats, but increased slightly following treatment with 17 beta-estradiol (E2) or 3 h after subsequent progesterone (P) injection. However, beta-Endo-like IR fiber density increased significantly 27 h after E2P treatment, and remained elevated 51 h after E2P treatment in the periventricular zone and in the medial portion of the medial preoptic nucleus, although the general distribution of fibers was unchanged. These results suggest that the density of MPOA beta-Endo innervation is normally Gonadal Steroid Hormone-dependent and that the medial MPOA contains greater opioid tone than the lateral MPOA regardless of the hormonal state. Furthermore, since beta-Endo-like IR fiber density remained elevated even though Gonadal Hormone levels decreased, additional factors might modulate the release or turnover of beta-Endo in the MPOA during normal estrous cycling.
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Gonadal Steroid Hormone REGULATION OF PROOPIOMELANOCORTIN GENE EXPRESSION IN ARCUATE NEURONS THAT INNERVATE THE MEDIAL PREOPTIC AREA OF THE RAT
Neuroendocrinology, 1995Co-Authors: Sun Cheung, Ronald P. HammerAbstract:The density of beta-endorphin (beta-endo)-like immunoreactive (IR) fibers in the medial preoptic area (MPOA) has been shown to vary across the estrous cycle and is Gonadal Steroid Hormone-dependent. These beta-endo-containing fibers are presumably projections of proopiomelanocortin (POMC) neurons which are located in the arcuate nucleus (ARC). POMC mRNA level varies across the estrous cycle in the ARC and its expression is differentially altered by Gonadal Steroid Hormones. However, it is unclear how Gonadal Steroids regulate POMC gene expression in ARC neurons that innervate the MPOA. Therefore, combined fluorogold (FG) retrograde neuronal labeling and in situ hybridization histochemistry were used to investigate the effects of Gonadal Steroid Hormone treatment on POMC gene expression in ARC neurons supplying the MPOA of ovariectomized (OVX) female rats. POMC-expressing cells were located in the ARC and median eminence (ME), wherein such neurons were significantly larger than unlabeled cells that surround them. A relatively greater number of ARC POMC neurons were observed to innervate the medial portion of the medial preoptic nucleus (MPN) than the lateral portion of the MPN. Estradiol (E2) and progesterone (P) treatment before FG injection did not affect the number of FG and POMC double-labeled neurons in the ARC, which suggests that Hormone treatment did not alter the number of POMC-expressing neurons projecting to the MPN. In OVX animals, ARC POMC mRNA labeling was relatively low, and increased significantly in neurons of the most rostral ARC region 48 h after E2 treatment. P administration enhanced and prolonged the effect of E2 in this group of ARC neurons. E2P treatment significantly increased POMC mRNA expression beginning 13 h after P injection in all but the most caudal ARC POMC neurons. Thereafter, E2P treatment gradually increased POMC mRNA expression for at least 1 additional day. Gonadal Steroid Hormone treatment apparently affects POMC mRNA expression uniformly in neurons of the same ARC subdivision without regard to their efferent targets. Diurnal variation of POMC mRNA expression is present only in the most rostral ARC region, which contains a population of E2-sensitive POMC neurons. The results suggest that the relatively greater beta-endo-like IR fiber density in the medial MPN is due to a greater number of POMC neurons innervating this region. The pattern of innervation of the MPN by POMC neurons is unaffected by Gonadal Steroid Hormone treatment, which appears to induce POMC expression in ARC neurons, and eventually to stimulate the synthesis and transport of beta-endo in POMC neuronal axons which project to the MPOA.(ABSTRACT TRUNCATED AT 400 WORDS)
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Gonadal Steroid Hormones and hypothalamic opioid circuitry
Hormones and behavior, 1994Co-Authors: Ronald P. Hammer, Lei Zhou, Sun CheungAbstract:Abstract Endogenous opioid peptides derived from several gene families are localized within hypothalamic regions known to be involved in the regulation of reproduction. For example, the proenkephalin gene products, met- and leu-enkephalin, and the proopiomelanocortin (POMC) gene product, β-endorphin, are found in the rat medial preoptic area (MPOA). Moreover, the expression of these peptides and their receptors varies across the estrous cycle in the female rat. We have examined the Gonadal Steroid regulation of μ-opiate receptors and opioid peptides in the MPOA, and POMC mRNA expression in neurons that innervate the MPOA. μ-Opiate receptors in the MPOA are sexually dimorphic and Gonadal Steroid Hormone-dependent. Hormonal priming of ovariectomized rats with estrogen and progesterone (P) upregulates MPOA μ-receptors 27, but not 3, hr after P treatment. Inhibition of protein synthesis during the first 6 hr after P prevents receptor upregulation, The density of β-endorphin fibers in the MPOA also increases following Hormone treatment, and POMC mRNA expression in neurons that innervate the MPOA is induced by Hormone treatment beginning 13 hr after P treatment. This delayed response might be ubiquitous among POMC neurons, as those innervating the median eminence also exhibit increased POMC mRNA expression along a similar time course. The results suggest that hormonal feedback regulates opioid peptides which act at μ-receptors in the MPOA to influence reproductive behavior and cyclicity. These opioid functions represent an important component in the complex regulatory processes which control reproduction.
Neil J. Maclusky - One of the best experts on this subject based on the ideXlab platform.
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sexually dimorphic effects of prenatal stress on cognition hormonal responses and central neurotransmitters
Endocrinology, 2004Co-Authors: Neil J. Maclusky, Rachel E Bowman, Yessenia Sarmiento, Maya Frankfurt, Marisa Gordon, Victoria N LuineAbstract:Exposure to stress during gestation results in physiological and behavioral alterations that persist into adulthood. This study examined the effects of prenatal stress on the postnatal expression of sexually differentiated cognitive, hormonal, and neurochemical profiles in male and female rats. Pregnant dams were subjected to restraint stress three times daily for 45 min during d 14–21 of pregnancy. The offspring of control and prenatally stressed dams were tested for anxiety-related and cognitive behaviors, stress and Gonadal Steroid Hormone levels, as well as monoamines and metabolite levels in selected brain regions. Postnatal testosterone levels (measured at 1 and 5 d) did not differ between controls and prenatally stressed animals. In adulthood, the serum corticosterone response to stress was attenuated in prenatally stressed females, eliminating the sex difference normally observed in this parameter. Prenatally stressed females exhibited higher anxiety levels, evidenced by longer open field entry la...
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In vitro labeling of Gonadal Steroid Hormone receptors in brain tissue sections
Steroids, 1995Co-Authors: Theodore J. Brown, Monika Sharma, Lawrence E. Heisler, Naznin Karsan, Michael J. Walters, Neil J. MacluskyAbstract:Autoradiographic methods have been developed for measurement of Gonadal Steroid receptors in situ in brain tissue sections. Based on principles established previously for estrogen receptors in the rat brain using a 125I-labeled ligand, procedures have been developed for in vitro labeling of estrogen, androgen, and progestin receptors with commercially available tritiated ligands. Addition of protamine sulfate to the incubation buffer precipitates the receptors in situ in the tissue sections, allowing them to be detected autoradiographically after incubation with labeled Steroid and subsequent washing to remove unbound and nonspecifically bound ligand. Occupied and unoccupied estrogen receptors can be measured selectively using appropriately modified incubation conditions. In the case of androgen and progestin receptors, unoccupied receptors are readily detected by in vitro labeling of tissue sections, but occupied receptors do not appear to label efficiently. Preliminary data suggest that these methods should be equally applicable to a variety of laboratory animals, including the rat, mouse, guinea pig, and monkey.
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estrogen receptors colocalize with low affinity nerve growth factor receptors in cholinergic neurons of the basal forebrain
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: C D Toranallerand, Theodore J. Brown, Rajesh C Miranda, W D L Bentham, Farida Sohrabji, Richard B Hochberg, Neil J. MacluskyAbstract:Abstract The rodent and primate basal forebrain is a target of a family of endogenous peptide signaling molecules, the neurotrophins--nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3--and of the Gonadal Steroid Hormone estrogen, both of which have been implicated in cholinergic function. To investigate whether or not these ligands may act on the same neurons in the developing and adult rodent basal forebrain, we combined autoradiography with 125I-labeled estrogen and either nonisotopic in situ hybridization histochemistry or immunohistochemistry. We now report colocalization of intranuclear estrogen binding sites with the mRNA and immunoreactive protein for the low-affinity nerve growth factor receptor, which binds all three neurotrophins, and for the cholinergic marker enzyme choline acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6). Colocalization of estrogen and low-affinity nerve growth factor receptors implies that their ligands may act on the same neuron, perhaps synergistically, to regulate the expression of specific genes or gene networks that may influence neuronal survival, differentiation, regeneration, and plasticity. That cholinergic neurons in brain regions subserving cognitive functions may be regulated not only by the neurotrophins but also by estrogen may have considerable relevance for the development and maintenance of neural substrates of cognition. If estrogen-neurotrophin interactions are important for survival of target neurons, then clinical conditions associated with estrogen deficiency could contribute to the atrophy or death of these neurons. These findings have implications for the subsequent decline in those differentiated neural functions associated with aging and Alzheimer disease.