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Robert A. Steiner - One of the best experts on this subject based on the ideXlab platform.

  • doi: 10.1210/en.2005-1282 Minireview: Kisspeptin Neurons as Central Processors in the Regulation of Gonadotropin-Releasing Hormone Secretion
    2013
    Co-Authors: Heather M Dungan, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene encodes a family of peptides called kisspeptins, which bind to the G protein-coupled receptor GPR54. Kisspeptin(s) and its receptor are expressed in the forebrain, and the discovery that mice and humans lacking a functional GPR54 fail to undergo puberty and exhibit hypogonadotropic hypogonadism implies that kisspeptin signaling plays an essential role in reproduction. Studies in several mammalian species have shown that kisspeptins stimulate the secretion of gonadotropins from the pituitary by stimulating the release of GnRH from the forebrain after the activation of GPR54, which is expressed by GnRH neurons. Kisspeptin is expressed abundantly in the arcuate Nucleus (Arc) and the Anteroventral Periventricular Nucleus (AVPV) of the forebrain. Both estradiol and testosterone regulate the expression of the Kiss1 gene in the Arc and AVPV; however, the response of the Kiss1 gen

  • REPRODUCTION REVIEW Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling
    2013
    Co-Authors: Jeremy Troy Smith, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate Nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the Anteroventral Periventricular Nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male)

  • the role of kisspeptins and gpr54 in the neuroendocrine regulation of reproduction
    Annual Review of Physiology, 2008
    Co-Authors: Simina M Popa, Donald K. Clifton, Robert A. Steiner
    Abstract:

    Neurons that produce gonadotropin-releasing hormone (GnRH) reside in the basal forebrain and drive reproductive function in mammals. Understanding the circuitry that regulates GnRH neurons is fundamental to comprehending the neuroendocrine control of puberty and reproduction in the adult. This review focuses on a family of neuropeptides encoded by the Kiss1 gene, the kisspeptins, and their cognate receptor, GPR54, which have been implicated in the regulation of GnRH secretion. Kisspeptins are potent secretagogues for GnRH, and the Kiss1 gene is a target for regulation by gonadal steroids (e.g., estradiol and testosterone), metabolic factors (e.g., leptin), photoperiod, and season. Kiss1 neurons in the arcuate Nucleus may regulate the negative feedback effect of gonadal steroids on GnRH and gonadotropin secretion in both sexes. The expression of Kiss1 in the Anteroventral Periventricular Nucleus (AVPV) is sexually dimorphic, and Kiss1 neurons in the AVPV may participate in the generation of the preovulatory GnRH/luteinizing hormone (LH) surge in the female rodent. Kiss1 neurons have emerged as primary transducers of internal and environmental cues to regulate the neuroendocrine reproductive axis.

  • regulation of the neuroendocrine reproductive axis by kisspeptin gpr54 signaling
    Reproduction, 2006
    Co-Authors: Jeremy Troy Smith, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate Nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the Anteroventral Periventricular Nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male).

  • minireview kisspeptin neurons as central processors in the regulation of gonadotropin releasing hormone secretion
    Endocrinology, 2006
    Co-Authors: Heather M Dungan, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene encodes a family of peptides called kisspeptins, which bind to the G protein-coupled receptor GPR54. Kisspeptin(s) and its receptor are expressed in the forebrain, and the discovery that mice and humans lacking a functional GPR54 fail to undergo puberty and exhibit hypogonadotropic hypogonadism implies that kisspeptin signaling plays an essential role in reproduction. Studies in several mammalian species have shown that kisspeptins stimulate the secretion of gonadotropins from the pituitary by stimulating the release of GnRH from the forebrain after the activation of GPR54, which is expressed by GnRH neurons. Kisspeptin is expressed abundantly in the arcuate Nucleus (Arc) and the Anteroventral Periventricular Nucleus (AVPV) of the forebrain. Both estradiol and testosterone regulate the expression of the Kiss1 gene in the Arc and AVPV; however, the response of the Kiss1 gene to these steroids is exactly opposite between these two nuclei. Estradiol and testosterone down-regulate Kiss1 mRNA in...

Richard B Simerly - One of the best experts on this subject based on the ideXlab platform.

  • Hormonal Regulation of Glutamate Receptor Gene Expression in the Anteroventral Periventricular Nucleus of the Hypothalamus
    2013
    Co-Authors: Frederique Varoqueaux, Richard B Simerly
    Abstract:

    Glutamate plays an important role in mediating the positive feedback effects of ovarian steroids on gonadotropin secretion, and the preoptic region of the hypothalamus is a likely site of action of glutamate. The Anteroventral Periventricular Nucleus (AVPV) of the preoptic region is an essential part of neural pathways mediating hormonal feedback on gonadotropin secretion, and it appears to provide direct inputs to gonadotropin releasing hormone (GnRH)-containing neurons. Immunohistochemistry and in situ hybridization were used in this study to define the distribution and hormonal regulation of glutamate receptor subtypes in the AVPV of juvenile female rats. Neurons that express the NMDAR1 receptor subtype are abundant in the AVPV, as are cells that express AMPA receptor subtypes (GluR1, GluR2, and GluR3 but not GluR4), and the AVPV appears to contain a dense plexus of NMDAR1-immunoreactiv

  • Target-Dependent Sexual Differentiation of a Limbic–Hypothalamic Neural Pathway
    2013
    Co-Authors: Maria A. Ibanez, Richard B Simerly
    Abstract:

    Neural pathways between sexually dimorphic forebrain regions develop under the influence of sex steroid hormones during the perinatal period, but how these hormones specify precise sexspecific patterns of connectivity is unknown. A heterochronic coculture system was used to demonstrate that sex steroid hormones direct development of a sexually dimorphic limbic– hypothalamic neural pathway through a target-dependent mechanism. Explants of the principal Nucleus of the bed nuclei of the stria terminalis (BSTp) extend neurites toward explants of the Anteroventral Periventricular Nucleus (AVPV) derived from male but not female rats. Coculture of BSTp explants from male rats with AVPV explants derived from females treated in vivo with testosterone for 9dresulted in a high density of neurites extending from the BSTp to the AVPV explant, as was the case when the BSTp explants were derived from females and th

  • Development of a Sexually Dimorphic Projection from the Bed Nuclei of the Stria Terminalis to the Anteroventral Periventricular Nucleus in the Rat
    2013
    Co-Authors: Leslie A Hutton, Richard B Simerly
    Abstract:

    The principal Nucleus of the bed nuclei of the stria terminalis (BSTp) is larger in male rats and conveys olfactory information relevant for reproduction to the hypothalamus. In males, the BSTp provides a massive projection to the Anteroventral Periventricular Nucleus of the preoptic region (AVPV), which in contrast to most sexually dimorphic nuclei contains more neurons in female rats. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the BSTp of adult female rats failed to demonstrate the strong projection to the AVPV observed previously in males. The ontogeny of this robust sex difference was examined by using the axonal marker DiI. The projection from the BSTp to the AVPV is established between postnatal day 9 (P9) and P10 in male rats and seems to be maintained during the juvenile period. Although labeled fibers extended from the BSTp toward the preoptic region in both male and female neonates, a similar connection with the AVPV was not apparent in female rats at any of the ages studied, and the density of labeled axons in the AVPV of P10 males was 20-fold greater than that of P10 females. A projection from the BSTp to the medial preoptic Nucleus was also weaker in females but was much more substantial than that to the AVPV. These findings suggest that a sex- and region-specific activity influences the development of the projection from the BSTp to the AVPV, producing a sexually dimorphic architecture in pathways that convey olfactory information to the hypothalamus. Key words: sexual differentiation; preoptic region; DiI; connections; dimorphic; development; bed Nucleus of the stria terminali

  • ontogeny of the projections from the Anteroventral Periventricular Nucleus of the hypothalamus in the female rat
    The Journal of Comparative Neurology, 2006
    Co-Authors: Eva K Polston, Richard B Simerly
    Abstract:

    Neurons in the Anteroventral Periventricular Nucleus of the hypothalamus (AVPV) mediate a variety of autonomic functions. In adults they primarily innervate neuroendocrine nuclei in the Periventricular zone of the hypothalamus, including the paraventricular and arcuate nuclei (PVH, ARH). Ascending projections from the AVPV also provide inputs to the ventrolateral septum (LSv) and the principal division of the bed nuclei of the stria terminalis (BSTp). Consistent with a role in regulating preovulatory luteinizing hormone secretion, rostral projections from the AVPV contact gonadotropin-releasing hormone (GnRH) neurons surrounding the vascular organ of the lamina terminalis (OVLT). To study the development of these pathways, we placed implants of the lipophilic tracers DiI and CMDiI into the AVPV of female rats ranging in age from embryonic day 19 (E19) through adulthood. The earliest projections targeted a population of GnRH neurons, with apparent contacts from labeled fibers observed as early as E19. These connections appeared to be fully developed before birth, as similar numbers of appositions from AVPV projections onto the GnRH-immunoreactive cells were observed at all ages examined. Caudal projections were delayed relative to projections to the OVLT. Labeled AVPV fibers reached the PVH during the first postnatal week, and fibers targeting the BSTp and LSv were not observed until the second and third postnatal weeks, respectively. Labeled AVPV fibers were not seen in the ARH of animals at any age. Our results demonstrate that projections from the AVPV develop with both spatial and temporal specificity, innervating each target with a unique developmental profile.

  • neurons in the principal Nucleus of the bed nuclei of the stria terminalis provide a sexually dimorphic gabaergic input to the Anteroventral Periventricular Nucleus of the hypothalamus
    Neuroscience, 2004
    Co-Authors: Eva K Polston, Richard B Simerly
    Abstract:

    Neurons of the principal Nucleus of the bed nuclei of the stria terminalis (BSTp) process pheromonal and viscerosensory stimuli associated with reproduction and relay this information to preoptic and hypothalamic cell groups that regulate reproductive function. The Anteroventral Periventricular Nucleus of the hypothalamus (AVPV), a Nucleus involved in the regulation of gonadotropin secretory patterns, receives dense projections from BSTp neurons in males but not in females. By injecting the anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHAL), into the BSTp of rats and immunohistochemically colocalizing the GABA synthetic enzyme, GAD65, to PHAL-immunoreactive fibers in the AVPV, we tested the hypothesis that these sex-specific projections arise from BSTp neurons that synthesize the inhibitory neurotransmitter GABA. Although dense GAD65-immunoreactive fiber terminals were observed in both the male and female AVPV, higher numbers of GAD65-labeled terminals were found in the male, and those localized to PHAL-immunoreactive fibers were seen almost exclusively in males. Treatment of newborn females with testosterone or neonatal orchidectomy of males reversed these sex differences, while GAD65-immunoreactivity in the AVPV was not altered in response to exogenous hormone treatments administered to peripubertal animals. Our results suggest that projections from BSTp neurons constitute a stable, sex-specific GABAergic input to the AVPV that is patterned permanently by perinatal hormone exposure.

Kei-ichiro Maeda - One of the best experts on this subject based on the ideXlab platform.

  • Mating-induced increase in Kiss1 mRNA expression in the Anteroventral Periventricular Nucleus prior to an increase in LH and testosterone release in male rats.
    The Journal of reproduction and development, 2020
    Co-Authors: Youki Watanabe, Yoshihisa Uenoyama, Kei-ichiro Maeda, Kana Ikegami, Sho Nakamura, Hitoshi Ozawa, Naoko Inoue
    Abstract:

    Kisspeptin has an indispensable role in gonadotropin-releasing hormone/gonadotropin secretion in mammals. In rodents, kisspeptin neurons are located in distinct brain regions, namely the Anteroventral Periventricular Nucleus-Periventricular Nucleus continuum (AVPV/PeN), arcuate Nucleus (ARC), and medial amygdala (MeA). Among them, the physiological role of AVPV/PeN kisspeptin neurons in males has not been clarified yet. The present study aims to investigate the acute effects of the olfactory and/or mating stimulus with a female rat on hypothalamic and MeA Kiss1 mRNA expression, plasma luteinizing hormone (LH) and testosterone levels in male rats. Intact male rats were exposed to the following stimuli: exposure to clean bedding; exposure to female-soiled bedding as a female-olfactory stimulus; exposure to female-soiled bedding and mating stimulus with a female rat. The mating stimulus significantly increased the number of the AVPV/PeN Kiss1 mRNA-expressing cells in males within 5 minutes after the exposure, and significantly increased LH and testosterone levels, followed by an increase in male sexual behavior. Whereas, the males exposed to female-soiled bedding showed a moderate increase in LH levels and no significant change in testosterone levels and the number of the AVPV/PeN Kiss1 mRNA-expressing cells. Importantly, none of the stimuli affected the number of Kiss1 mRNA-expressing cells in the ARC and MeA. These results suggest that the mating-induced increase in AVPV/PeN Kiss1 mRNA expression may be, at least partly, involved in stimulating LH and testosterone release, and might consequently ensure male mating behavior. This study would be the first report suggesting that the AVPV/PeN kisspeptin neurons in males may play a physiological role in ensuring male reproductive performance.

  • circadian transcriptional factor dbp regulates expression of kiss1 in the Anteroventral Periventricular Nucleus
    Molecular and Cellular Endocrinology, 2011
    Co-Authors: Shigehito Kaga, Kei-ichiro Maeda, Hiroko Tsukamura, Kinji Inoue, Jun Tsubomizu, Jun Fujisaki, Akikazu Mochiduki, Takafumi Sakai, Akihito Adachi
    Abstract:

    The expression of Kiss1 in the Anteroventral Periventricular Nucleus (AVPV) and its product, metastin/kisspeptin, show a circadian pattern with a peak in the evening, which shows a strong phase relationship with the time of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge in rodents. Here we report that a circadian transcriptional factor, albumin D-site binding protein (Dbp), was able to trigger mKiss1 transcription via the D-box, and this effect was combined with those of estrogen receptor α (ERα) and its ligand, estrogen. A histological study demonstrated that some cells in the AVPV co-expressed Dbp with ERα in adult female rats. Expression of ERα was not rhythmic in the AVPV, however, mRNA of Dbp in the AVPV accumulated with a robust diurnal rhythm in proestrus, but not on the first day of diestrus. Thus, these results suggest that Dbp and estrogen regulate the expression of Kiss1 in the AVPV, thereby mediating the GnRH/LH surge.

  • Sexual differentiation of kisspeptin neurons responsible for sex difference in gonadotropin release in rats.
    Annals of the New York Academy of Sciences, 2010
    Co-Authors: Hiroko Tsukamura, Tamami Homma, Junko Tomikawa, Yoshihisa Uenoyama, Kei-ichiro Maeda
    Abstract:

    The brain mechanism regulating GnRH/luteinizing hormone (LH) release is sexually differentiated in rodents. Estrogen induces a GnRH/LH surge in females but not in males. Kisspeptin neurons in the Anteroventral Periventricular Nucleus (AVPV) have been reported to be sexually dimorphic and suggested to be involved in the GnRH/LH surge generation. Neonatal testicular androgen may cause the reduction of AVPV kisspeptin expression and a lack of LH surge in male rats. Thus, it is plausible that perinatal testicular androgen causes defeminization of the AVPV kisspeptin system, resulting in the loss of the surge system in male rats.

  • kisspeptin metastin a key molecule controlling two modes of gonadotrophin releasing hormone luteinising hormone release in female rats
    Journal of Neuroendocrinology, 2009
    Co-Authors: Yoshihisa Uenoyama, Hiroko Tsukamura, Kei-ichiro Maeda
    Abstract:

    Kisspeptin (also known as metastin), a hypothalamic peptide, has attracted attention as a key molecule in the release of gonadotrophin-releasing hormone (GnRH) in various mammalian species, such as rodents, sheep and primates. Two populations of kisspeptin neurones in the brain may control two modes of GnRH release to time the onset of puberty and regulate oestrous cyclicity in rats and mice. One population of kisspeptin neurones, located in the Anteroventral Periventricular Nucleus, appears to be responsible for the induction of the GnRH surge that leads to the luteinising hormone surge and ovulation. The other, located in the hypothalamic arcuate Nucleus, appears to be involved in generating GnRH pulses, resulting in luteinising hormone pulses followed by follicular development and steroidogenesis in the ovary. The present review focuses on the physiological role of the two populations of kisspeptin neurones in controlling gonadal functions by generating the two modes of GnRH release in a female rat model.

  • physiological role of metastin kisspeptin in regulating gonadotropin releasing hormone gnrh secretion in female rats
    Peptides, 2009
    Co-Authors: Satoshi Ohkura, Tamami Homma, Yoshihisa Uenoyama, Kei-ichiro Maeda, Naoko Inoue, Shunji Yamada, Kenji Takase, Hiroko Tsukamura
    Abstract:

    Various studies have attempted to unravel the physiological role of metastin/kisspeptin in the control of gonadotropin-releasing hormone (GnRH) release. A number of evidences suggested that the population of metastin/kisspeptin neurons in the Anteroventral Periventricular Nucleus (AVPV) is involved in generating a GnRH surge to induce ovulation in rodents, and thus the target of estrogen positive feedback. Females have an obvious metastin/kisspeptin neuronal population in the AVPV, but males have only a few cell bodies in the Nucleus, suggesting that the absence of the surge-generating mechanism or positive feedback action in males is due to the limited AVPV metastin/kisspeptin neuronal population. On the other hand, the arcuate Nucleus (ARC) metastin/kisspeptin neuronal population is considered to be involved in the regulation of tonic GnRH release. The ARC metastin/kisspeptin neurons show no sex difference in their expression, which is suppressed by gonadal steroids in both sexes. Thus, the ARC population of metastin/kisspeptin neurons is a target of estrogen negative feedback action on tonic GnRH release. The lactating rat model provided further evidence indicating that ARC metastin/kisspeptin neurons are involved in GnRH pulse generation, because pulsatile release of luteinizing hormone (LH) is profoundly suppressed by suckling stimulus and the LH pulse suppression is well associated with the suppression of ARC metastin/kisspeptin and KiSS-1 gene expression in lactating rats.

Hiroko Tsukamura - One of the best experts on this subject based on the ideXlab platform.

  • Kisspeptin Neurons and Estrogen–Estrogen Receptor α Signaling: Unraveling the Mystery of Steroid Feedback System Regulating Mammalian Reproduction
    'MDPI AG', 2021
    Co-Authors: Yoshihisa Uenoyama, Sho Nakamura, Naoko Inoue, Hiroko Tsukamura
    Abstract:

    Estrogen produced by ovarian follicles plays a key role in the central mechanisms controlling reproduction via regulation of gonadotropin-releasing hormone (GnRH) release by its negative and positive feedback actions in female mammals. It has been well accepted that estrogen receptor α (ERα) mediates both estrogen feedback actions, but precise targets had remained as a mystery for decades. Ever since the discovery of kisspeptin neurons as afferent ERα-expressing neurons to govern GnRH neurons, the mechanisms mediating estrogen feedback are gradually being unraveled. The present article overviews the role of kisspeptin neurons in the arcuate Nucleus (ARC), which are considered to drive pulsatile GnRH/gonadotropin release and folliculogenesis, in mediating the estrogen negative feedback action, and the role of kisspeptin neurons located in the Anteroventral Periventricular Nucleus-Periventricular Nucleus (AVPV-PeN), which are thought to drive GnRH/luteinizing hormone (LH) surge and consequent ovulation, in mediating the estrogen positive feedback action. This implication has been confirmed by the studies showing that estrogen-bound ERα down- and up-regulates kisspeptin gene (Kiss1) expression in the ARC and AVPV-PeN kisspeptin neurons, respectively. The article also provides the molecular and epigenetic mechanisms regulating Kiss1 expression in kisspeptin neurons by estrogen. Further, afferent ERα-expressing neurons that may regulate kisspeptin release are discussed

  • Co‐expression of the calcitonin receptor gene in the hypothalamic kisspeptin neurons in female rats
    'Wiley', 2018
    Co-Authors: Nahoko Ieda, Yoshihisa Uenoyama, Naoko Inoue, Narumi Kawai, Hirotaka Ishii, Kunio Ihara, Hiroko Tsukamura
    Abstract:

    Abstract Purpose Hypothalamic kisspeptin neurons are considered to play a critical role in regulating mammalian reproduction and integrating humoral and neuronal inputs that control gonadotropin‐releasing hormone (GnRH)/gonadotropin release. The present study aimed to investigate the upstream regulator candidates for kisspeptin neurons. Methods Visualized kisspeptin neurons that were taken from the arcuate Nucleus (ARC) of Kiss1‐tdTomato rats were subjected to next‐generation sequencing (NGS) analysis. In situ hybridization (ISH) for the calcitonin receptor gene (Calcr) was performed throughout the whole forebrain of ovariectomized wild‐type female rats that had been implanted with a negative feedback level of estrogen, because the Calcr expression was evident in the ARC kisspeptin neurons from the NGS analysis. Then, a double ISH was performed for the Calcr and kisspeptin gene (Kiss1) in the brain regions, containing either the Anteroventral Periventricular Nucleus (AVPV) or ARC of the female rats. Results The NGS analysis revealed that the Calcr was highly expressed in the ARC kisspeptin neurons. It was found that the Calcr was co‐expressed in 12% and 22% of the Kiss1‐expressing cells in the ARC and AVPV, respectively. Conclusion The present study suggests that calcitonin receptor signaling could be involved in the regulation of reproductive function through the direct control of the ARC and/or AVPV kisspeptin neurons, and then GnRH/gonadotropin release

  • circadian transcriptional factor dbp regulates expression of kiss1 in the Anteroventral Periventricular Nucleus
    Molecular and Cellular Endocrinology, 2011
    Co-Authors: Shigehito Kaga, Kei-ichiro Maeda, Hiroko Tsukamura, Kinji Inoue, Jun Tsubomizu, Jun Fujisaki, Akikazu Mochiduki, Takafumi Sakai, Akihito Adachi
    Abstract:

    The expression of Kiss1 in the Anteroventral Periventricular Nucleus (AVPV) and its product, metastin/kisspeptin, show a circadian pattern with a peak in the evening, which shows a strong phase relationship with the time of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) surge in rodents. Here we report that a circadian transcriptional factor, albumin D-site binding protein (Dbp), was able to trigger mKiss1 transcription via the D-box, and this effect was combined with those of estrogen receptor α (ERα) and its ligand, estrogen. A histological study demonstrated that some cells in the AVPV co-expressed Dbp with ERα in adult female rats. Expression of ERα was not rhythmic in the AVPV, however, mRNA of Dbp in the AVPV accumulated with a robust diurnal rhythm in proestrus, but not on the first day of diestrus. Thus, these results suggest that Dbp and estrogen regulate the expression of Kiss1 in the AVPV, thereby mediating the GnRH/LH surge.

  • Sexual differentiation of kisspeptin neurons responsible for sex difference in gonadotropin release in rats.
    Annals of the New York Academy of Sciences, 2010
    Co-Authors: Hiroko Tsukamura, Tamami Homma, Junko Tomikawa, Yoshihisa Uenoyama, Kei-ichiro Maeda
    Abstract:

    The brain mechanism regulating GnRH/luteinizing hormone (LH) release is sexually differentiated in rodents. Estrogen induces a GnRH/LH surge in females but not in males. Kisspeptin neurons in the Anteroventral Periventricular Nucleus (AVPV) have been reported to be sexually dimorphic and suggested to be involved in the GnRH/LH surge generation. Neonatal testicular androgen may cause the reduction of AVPV kisspeptin expression and a lack of LH surge in male rats. Thus, it is plausible that perinatal testicular androgen causes defeminization of the AVPV kisspeptin system, resulting in the loss of the surge system in male rats.

  • kisspeptin metastin a key molecule controlling two modes of gonadotrophin releasing hormone luteinising hormone release in female rats
    Journal of Neuroendocrinology, 2009
    Co-Authors: Yoshihisa Uenoyama, Hiroko Tsukamura, Kei-ichiro Maeda
    Abstract:

    Kisspeptin (also known as metastin), a hypothalamic peptide, has attracted attention as a key molecule in the release of gonadotrophin-releasing hormone (GnRH) in various mammalian species, such as rodents, sheep and primates. Two populations of kisspeptin neurones in the brain may control two modes of GnRH release to time the onset of puberty and regulate oestrous cyclicity in rats and mice. One population of kisspeptin neurones, located in the Anteroventral Periventricular Nucleus, appears to be responsible for the induction of the GnRH surge that leads to the luteinising hormone surge and ovulation. The other, located in the hypothalamic arcuate Nucleus, appears to be involved in generating GnRH pulses, resulting in luteinising hormone pulses followed by follicular development and steroidogenesis in the ovary. The present review focuses on the physiological role of the two populations of kisspeptin neurones in controlling gonadal functions by generating the two modes of GnRH release in a female rat model.

Donald K. Clifton - One of the best experts on this subject based on the ideXlab platform.

  • doi: 10.1210/en.2005-1282 Minireview: Kisspeptin Neurons as Central Processors in the Regulation of Gonadotropin-Releasing Hormone Secretion
    2013
    Co-Authors: Heather M Dungan, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene encodes a family of peptides called kisspeptins, which bind to the G protein-coupled receptor GPR54. Kisspeptin(s) and its receptor are expressed in the forebrain, and the discovery that mice and humans lacking a functional GPR54 fail to undergo puberty and exhibit hypogonadotropic hypogonadism implies that kisspeptin signaling plays an essential role in reproduction. Studies in several mammalian species have shown that kisspeptins stimulate the secretion of gonadotropins from the pituitary by stimulating the release of GnRH from the forebrain after the activation of GPR54, which is expressed by GnRH neurons. Kisspeptin is expressed abundantly in the arcuate Nucleus (Arc) and the Anteroventral Periventricular Nucleus (AVPV) of the forebrain. Both estradiol and testosterone regulate the expression of the Kiss1 gene in the Arc and AVPV; however, the response of the Kiss1 gen

  • REPRODUCTION REVIEW Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling
    2013
    Co-Authors: Jeremy Troy Smith, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate Nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the Anteroventral Periventricular Nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male)

  • the role of kisspeptins and gpr54 in the neuroendocrine regulation of reproduction
    Annual Review of Physiology, 2008
    Co-Authors: Simina M Popa, Donald K. Clifton, Robert A. Steiner
    Abstract:

    Neurons that produce gonadotropin-releasing hormone (GnRH) reside in the basal forebrain and drive reproductive function in mammals. Understanding the circuitry that regulates GnRH neurons is fundamental to comprehending the neuroendocrine control of puberty and reproduction in the adult. This review focuses on a family of neuropeptides encoded by the Kiss1 gene, the kisspeptins, and their cognate receptor, GPR54, which have been implicated in the regulation of GnRH secretion. Kisspeptins are potent secretagogues for GnRH, and the Kiss1 gene is a target for regulation by gonadal steroids (e.g., estradiol and testosterone), metabolic factors (e.g., leptin), photoperiod, and season. Kiss1 neurons in the arcuate Nucleus may regulate the negative feedback effect of gonadal steroids on GnRH and gonadotropin secretion in both sexes. The expression of Kiss1 in the Anteroventral Periventricular Nucleus (AVPV) is sexually dimorphic, and Kiss1 neurons in the AVPV may participate in the generation of the preovulatory GnRH/luteinizing hormone (LH) surge in the female rodent. Kiss1 neurons have emerged as primary transducers of internal and environmental cues to regulate the neuroendocrine reproductive axis.

  • regulation of the neuroendocrine reproductive axis by kisspeptin gpr54 signaling
    Reproduction, 2006
    Co-Authors: Jeremy Troy Smith, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene codes for a family of peptides that act as endogenous ligands for the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility. Centrally administered kisspeptins stimulate gonadotropin secretion by acting directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in the brain through direct action on KiSS-1 neurons. In the arcuate Nucleus (Arc), sex steroids inhibit the expression of KiSS-1, suggesting that these neurons serve as a conduit for the negative feedback regulation of gonadotropin secretion. In the Anteroventral Periventricular Nucleus (AVPV), sex steroids induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may have a role in the preovulatory LH surge (in the female) or sexual behavior (in the male).

  • minireview kisspeptin neurons as central processors in the regulation of gonadotropin releasing hormone secretion
    Endocrinology, 2006
    Co-Authors: Heather M Dungan, Donald K. Clifton, Robert A. Steiner
    Abstract:

    The Kiss1 gene encodes a family of peptides called kisspeptins, which bind to the G protein-coupled receptor GPR54. Kisspeptin(s) and its receptor are expressed in the forebrain, and the discovery that mice and humans lacking a functional GPR54 fail to undergo puberty and exhibit hypogonadotropic hypogonadism implies that kisspeptin signaling plays an essential role in reproduction. Studies in several mammalian species have shown that kisspeptins stimulate the secretion of gonadotropins from the pituitary by stimulating the release of GnRH from the forebrain after the activation of GPR54, which is expressed by GnRH neurons. Kisspeptin is expressed abundantly in the arcuate Nucleus (Arc) and the Anteroventral Periventricular Nucleus (AVPV) of the forebrain. Both estradiol and testosterone regulate the expression of the Kiss1 gene in the Arc and AVPV; however, the response of the Kiss1 gene to these steroids is exactly opposite between these two nuclei. Estradiol and testosterone down-regulate Kiss1 mRNA in...