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Allan E Herbison - One of the best experts on this subject based on the ideXlab platform.
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electrical and morphological characteristics of anteroventral Periventricular Nucleus kisspeptin and other neurons in the female mouse
Endocrinology, 2010Co-Authors: Eric Ducret, Galina Gaidamaka, Allan E HerbisonAbstract:Neurons in the rodent anteroventral Periventricular Nucleus (AVPV) play a key role in integrating circadian and gonadal steroid hormone information in the control of fertility. In particular, estradiol-sensitive kisspeptin neurons located in the AVPV, and adjacent structures [together termed the rostral Periventricular area of the third ventricle (RP3V)], are critical for puberty onset and the preovulatory LH surge. The present study aimed to establish the morphological and electrical firing characteristics of RP3V neurons, including kisspeptin neurons, in the adult female mouse. Cell-attached electrical recordings, followed by juxtacellular dye filling, of 129 RP3V neurons in the acute brain slice preparation revealed these cells to exhibit multipolar (53%), bipolar (43%), or unipolar (4%) dendritic morphologies along with silent (16%), irregular (41%), bursting (25%), or tonic (34%) firing patterns. Postrecording immunocytochemistry identified 17 of 100 filled RP3V cells as being kisspeptin neurons, all...
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postnatal development of kisspeptin neurons in mouse hypothalamus sexual dimorphism and projections to gonadotropin releasing hormone neurons
Endocrinology, 2006Co-Authors: Jenny Clarkson, Allan E HerbisonAbstract:The neuropeptide kisspeptin has recently been implicated as having a critical role in the activation of the GnRH neurons to bring about puberty. We examined here the postnatal development of kisspeptin neuronal populations and their projections to GnRH neurons in the mouse. Three populations of kisspeptin neurons located in the 1) anteroventral Periventricular Nucleus (AVPV) and the preoptic Periventricular Nucleus (PeN), 2) dorsomedial hypothalamus, and 3) arcuate Nucleus were identified using an antisera raised against mouse kisspeptin-10. A marked 10-fold (P < 0.01), female-dominant sex difference in the numbers of kisspeptin neurons existed in the AVPV/PeN but not elsewhere. Kisspeptin neurons in the AVPV/PeN of both sexes displayed a similar pattern of postnatal development with no cells detected at postnatal day (P) 10, followed by increases from P25 to reach adult levels by puberty onset (P < 0.01; P31 females and P45 males). This pattern was not found in the dorsomedial hypothalamus or arcuate nuc...
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postnatal development of kisspeptin neurons in mouse hypothalamus sexual dimorphism and projections to gonadotropin releasing hormone neurons
Endocrinology, 2006Co-Authors: Jenny Clarkson, Allan E HerbisonAbstract:The neuropeptide kisspeptin has recently been implicated as having a critical role in the activation of the GnRH neurons to bring about puberty. We examined here the postnatal development of kisspeptin neuronal populations and their projections to GnRH neurons in the mouse. Three populations of kisspeptin neurons located in the 1) anteroventral Periventricular Nucleus (AVPV) and the preoptic Periventricular Nucleus (PeN), 2) dorsomedial hypothalamus, and 3) arcuate Nucleus were identified using an antisera raised against mouse kisspeptin-10. A marked 10-fold (P<0.01), female-dominant sex difference in the numbers of kisspeptin neurons existed in the AVPV/PeN but not elsewhere. Kisspeptin neurons in the AVPV/PeN of both sexes displayed a similar pattern of postnatal development with no cells detected at postnatal day (P) 10, followed by increases from P25 to reach adult levels by puberty onset (P<0.01; P31 females and P45 males). This pattern was not found in the dorsomedial hypothalamus or arcuate Nucleus. Dual immunofluorescence experiments demonstrated close appositions between kisspeptin fibers and GnRH neuron cell bodies that were first apparent at P25 and increased across postnatal development in both sexes. These studies demonstrate kisspeptin peptide expression in the mouse hypothalamus and reveal the postnatal development of a sexually dimorphic continuum of kisspeptin neurons within the AVPV and PeN. This Periventricular population of kisspeptin neurons reaches adult-like proportions at the time of puberty onset and is the likely source of the kisspeptin inputs to GnRH neurons.
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estrogen dependent ontogeny of sex differences in somatostatin neurons of the hypothalamic Periventricular Nucleus
Endocrinology, 1998Co-Authors: Sharon X Simonian, Hilary E Murray, Glenda Gillies, Allan E HerbisonAbstract:The sexually dimorphic profile of GH secretion is thought to be engendered by gonadal steroids acting in part on hypothalamic Periventricular somatostatin (SOM) neurons. The present study set out to examine and characterize the development of sex differences in these SOM neurons. In the first series of experiments, we used in situ hybridization to examine SOM messenger RNA (mRNA) expression within the Periventricular Nucleus (PeN) of male and female rats on postnatal day 1 (P1), P5, and P10. Cellular SOM mRNA content was found to increase from P1 to P10 in both sexes (P < 0.01), but was 24% (P < 0.05) and 38% (P < 0.01) higher in males on P5 and P10, respectively. A second series of experiments examined the SOM peptide content of the PeN in developing rats and found increasing levels from P1 to P10, with a 44% higher SOM content in males compared with females on P10 (P < 0.05). The third series of experiments questioned the role of gonadal steroids in engendering sex differences in SOM mRNA expression by determining the effects of neonatal gonadectomy (GDX) and replacement of dihydrotestosterone or estradiol benzoate. The SOM mRNA content of PeN neurons in P5 males gonadectomized on the day of birth was the same as that in P5 females and was significantly reduced compared with that in sham-operated P5 males (P < 0.05). Male rats GDX on P1 and treated with estradiol benzoate from P1 to P5 had cellular SOM mRNA levels similar to those in intact males on P5, whereas dihydrotestosterone treatment had no effect. Treatment of intact males with an androgen receptor antagonist, cyproterone acetate, on P1 had no effect on cellular SOM mRNA on P5, whereas male rats given the aromatase inhibitor 1,4,6-androstatriene-3,17-dione from P1 to P5 had lower (P < 0.05) SOM mRNA levels than controls. In the final set of experiments, dual labeling immunocytochemistry showed that SOM neurons in the PeN of P5 rats did not contain estrogen receptor-alpha, but expressed androgen receptors in a sexually dimorphic manner. These results demonstrate that a sex difference in SOM biosynthesis, which persists into adulthood, develops between P1 and P5 in PeN neurons. Despite the absence of estrogen receptor-alpha in these neurons, the organizational influence of testosterone only occurs after its aromatization to estrogen.
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sexually dimorphic expression of androgen receptor immunoreactivity by somatostatin neurones in rat hypothalamic Periventricular Nucleus and bed Nucleus of the stria terminalis
Journal of Neuroendocrinology, 1995Co-Authors: Allan E HerbisonAbstract:Gonadal steroids exert important regulatory actions on the hypothalamic neurones regulating growth hormone secretion and are believed to play a role in generating its sexually dimorphic pattern of secretion. Recent evidence indicates that estrogen actions on one of these neural populations, the Periventricular somatostatin (SOM) neurones, are likely to be indirect as they do not possess nuclear estrogen receptors in either sex although androgen receptors (ARs) have been reported within these cells in male rats. The present study has used double-labelling immunocytochemistry procedures to examine whether sex differences exist in AR expression by SOM neurones located in the Periventricular Nucleus and bed Nucleus of the stria terminalis (BNST). Within the hypothalamus, SOM-immunoreactive neurones were found concentrated in the Periventricular Nucleus while both anterior and posterior divisions of the BNST contained scattered populations of SOM cells. Cells immunoreactive for the AR were detected in all of these areas. Although the intensity of AR cell nuclei staining was equivalent in males and females in regions such as the lateral septum, the intensity of AR staining in many individual cells of the Periventricular Nucleus and posterior BNST of the female was reduced when compared with the male. Double-labelling experiments revealed that approximately 40% of Periventricular SOM neurones expressed AR immunoreactivity in the male compared with significantly (P < 0.01) fewer cells in the female (approximately 7%). In the BNST, double-labelled cells were only detected within the principle encapsulated, interfascicular and transverse nuclei of its posterior division. Approximately 60% of SOM cells in these nuclei expressed AR immunoreactivity in the male while significantly (P < 0.01) fewer did so in the female (approximately 25%). These results indicate that substantial sex differences exist in AR expression by SOM neurones in both the Periventricular Nucleus and BNST. Such differences in AR expression by Periventricular SOM cells may contribute to their sexuality dimorphic nature and, consequently, sex differences in growth hormone secretion.
Richard B Simerly - One of the best experts on this subject based on the ideXlab platform.
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Development of a Sexually Dimorphic Projection from the Bed Nuclei of the Stria Terminalis to the Anteroventral Periventricular Nucleus in the Rat
2013Co-Authors: Leslie A Hutton, Richard B SimerlyAbstract: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
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ontogeny of the projections from the anteroventral Periventricular Nucleus of the hypothalamus in the female rat
The Journal of Comparative Neurology, 2006Co-Authors: Eva K Polston, Richard B SimerlyAbstract: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.
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hormonal regulation of glutamate receptor gene expression in the anteroventral Periventricular Nucleus of the hypothalamus
The Journal of Neuroscience, 1999Co-Authors: Frederique Varoqueaux, Richard B SimerlyAbstract: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-immunoreactive presynaptic terminals. However, AVPV neurons do not seem to express detectable levels of kainate receptor (GluR5, GluR6, and GluR7) or metabotropic receptor (mGluR1–6) subtypes. Treatment of ovariectomized juvenile rats with estradiol induced expression of GluR1 mRNA but did not alter levels of GluR2 or GluR3 mRNA. Treatment of estrogen-primed ovariectomized juvenile rats with progesterone caused an initial increase in GluR1 mRNA expression, followed by a small decrease 24 hr after treatment. In contrast, estrogen appears to suppress levels of NMDAR1 mRNA in the AVPV, which remained unchanged after progesterone treatment. Thus, one mechanism whereby ovarian steroids may provide positive feedback to GnRH neurons is by altering the sensitivity of AVPV neurons to glutamatergic activation.
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development of a sexually dimorphic projection from the bed nuclei of the stria terminalis to the anteroventral Periventricular Nucleus in the rat
The Journal of Neuroscience, 1998Co-Authors: Leslie A Hutton, Richard B SimerlyAbstract: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.
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projections of the sexually dimorphic anteroventral Periventricular Nucleus in the female rat
The Journal of Comparative Neurology, 1997Co-Authors: Richard B SimerlyAbstract:The anteroventral Periventricular Nucleus of the hypothalamus (AVPV) is a sexually dimorphic Nucleus in the preoptic region that appears to be a nodal point in forebrain circuits, mediating hormonal feedback on gonadotropin secretion. The results of anterograde transport experiments indicate that the AVPV sends ascending projections to the ventral part of the lateral septal Nucleus, the parastrial Nucleus, and the region adjacent to the vascular organ of the lamina terminalis (OVLT) that contains a subpopulation of gonadotropin releasing hormone (GnRH)-containing neurons. The majority of projections from the AVPV pass caudally through the Periventricular zone of the hypothalamus and form dense terminal fields in the Periventricular nuclei, parvicellular parts of the paraventricular Nucleus, and in the arcuate Nucleus. Inputs to medial zone nuclei are more limited, with substantial projections to only the medial preoptic and dorsomedial nuclei. The AVPV sends few projections to the caudal brainstem, but terminals were observed reliably in the periaqueductal gray and medial part of the Nucleus of the solitary tract. Anterograde double-labeling experiments demonstrate terminals derived from neurons in the AVPV in close apposition to GnRH-containing neurons in the preoptic region, and to dopaminergic neurons in the arcuate Nucleus. Thus, the organization of projections from the AVPV in female rats suggests that neurons in this Nucleus may influence the secretion of luteinizing hormone and prolactin through direct projections to GnRH neurons and tuberoinfundibular dopaminergic neurons.
Clive W Coen - One of the best experts on this subject based on the ideXlab platform.
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fasting reduces kiss 1 expression in the anteroventral Periventricular Nucleus avpv effects of fasting on the expression of kiss 1 and neuropeptide y in the avpv or arcuate Nucleus of female rats
Journal of Neuroendocrinology, 2008Co-Authors: Theodosis Kalamatianos, Joel D Hahn, S E Grimshaw, Ravi Poorun, Clive W CoenAbstract:Changes in metabolic state, such as those induced by fasting, have profound effects on reproduction. In rats, the time-course over which fasting inhibits luteinising hormone (LH) release is reduced to 48 h by the presence of oestradiol-17beta (E(2)). Hypothalamic kisspeptin plays a key role in mediating the actions of E(2) on gonadotrophin-releasing hormone (GnRH) neurones, and thereby promotes LH release. KiSS-1-expressing neurones are found in the anteroventral Periventricular Nucleus (AVPV) and arcuate Nucleus (ARC). Extensive evidence implicates the AVPV in GnRH release and the ARC in energy balance. The latter Nucleus also contains neurones that express neuropeptide Y (NPY), an orexigenic peptide implicated in GnRH control. To elucidate the involvement of kisspeptin and/or NPY in hypothalamic responses to fasting, their expression was quantified by in situ hybridisation histochemistry in ovariectomised rats, with or without E(2) replacement, before and after 48 h of fasting. In the presence of E(2), but not in its absence, the fasting suppressed plasma LH. In the AVPV, the low level of KiSS-1 expression found in the absence of E(2) was unaffected by fasting. By contrast, the elevated level found in the presence of E(2) was suppressed by fasting. Independent of E(2), fasting had no effect on KiSS-1 expression in the ARC, but increased NPY expression at that site. The present study has identified the AVPV as a site at which KiSS-1 expression can be influenced by fasting. The results suggest that inhibition of KiSS-1 expression in the AVPV may be a significant factor in restraining the gonadotrophic axis in response to negative energy balance in the presence of oestrogen. The extent to which the concurrent rise in NPY expression in the ARC may contribute to the suppression of LH release by influencing AVPV kisspeptin neurones, directly or indirectly, or by actions independent of kisspeptin, remains to be established.
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neonatal stimulation of 5 ht2 receptors reduces androgen receptor expression in the rat anteroventral Periventricular Nucleus and sexually dimorphic preoptic area
European Journal of Neuroscience, 2008Co-Authors: C L Dakin, C A Wilson, Imre Kallo, Clive W Coen, D C DaviesAbstract:Masculinization of the brain is dependent upon a perinatal surge in testosterone. It also requires a transient decrease in hypothalamic 5-HT concentration and turnover and an increase in androgen receptor (AR) expression during the second postnatal week. We have previously shown that increasing 5-HT activity over this period in male or androgenized female rats feminizes their adult behaviour and also feminizes the size of their anteroventral Periventricular Nucleus (AVPV) and sexually dimorphic Nucleus of the preoptic area (SDN-POA). To investigate the role of 5-HT in sexual differentiation of the brain, 5-HT activity was raised over postnatal days 8-16 in male, female and androgenized female rats by daily administration of the 5-HT 2 receptor agonist (-)[2,5 dimethoxy-4-iodophenyl]-2-amino propane hydrochloride [(-)DOI]. By postnatal day 18, the size of the AVPV and SDN-POA was sexually dimorphic; their sizes were feminized by (-)DOI treatment. In the absence of (-)DOI treatment, there were significantly more AR-immunoreactive cells in the AVPV of males, and in the SDN-POA of males and androgenized females, than in those of females on postnatal day 18. (-)DOI treatment reduced the number of AR-immunoreactive cells in the AVPV and SDN-POA of males and androgenized females, but not of females, by postnatal day 18. These results suggest that 5-HT 2 receptor activation can influence sexual differentiation of the brain by controlling AR expression.
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comparative study of the sources of neuronal projections to the site of gonadotrophin releasing hormone perikarya and to the anteroventral Periventricular Nucleus in female rats
The Journal of Comparative Neurology, 2006Co-Authors: Joel D Hahn, Clive W CoenAbstract:The rat ovulatory cycle is dependent on the preoptic region encompassing the gonadotrophin-releasing hormone (GnRH) perikarya and the anteroventral Periventricular Nucleus (AVPV). Retrograde tract tracing was used to identify and compare the sources of inputs to these sites in female rats. Within the telencephalon and diencephalon, the incidence of retrograde labelling from both sites was moderate to abundant in the ventral lateral septum, posteromedial bed Nucleus of the stria terminalis, amygdalohippocampal area and the Periventricular, medial preoptic, anterodorsal preoptic, dorsomedial suprachiasmatic, arcuate, and posterior ventrolateral ventromedial hypothalamic nuclei. In these regions, the incidence of retrograde labelling was either greater from the AVPV than from the GnRH perikarya site or similar from both sites. In the medial amygdaloid, parastrial, striohypothalamic, and ventral premammillary nuclei, the retrograde labelling from the AVPV greatly exceeded the sparse incidence from the GnRH perikarya site. In contrast, retrograde labelling from the GnRH perikarya site predominated in the median preoptic, lateroanterior and dorsomedial hypothalamic nuclei, subparaventricular zone, and retrochiasmatic area; it was abundant in the AVPV. Caudal to the diencephalon, retrograde labelling from either site was sparse, except in the lateral parabrachial Nucleus, which displayed a particularly high incidence from the GnRH perikarya site. Other mesencephalic regions labelled from either site included the periaqueductal gray and dorsal and median raphe nuclei. The most caudal labelling was found in the ventrolateral medulla and region of the solitary tract Nucleus; this was almost exclusively from the GnRH perikarya site. These findings further elucidate the neuroanatomical connections underlying the control of the ovulatory cycle.
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cellular expression of v1a vasopressin receptor mrna in the female rat preoptic area effects of oestrogen
Journal of Neuroendocrinology, 2004Co-Authors: Theodosis Kalamatianos, Imre Kallo, M L Goubillon, Clive W CoenAbstract:The preovulatory luteinizing hormone (LH) surge in female rats is dependent upon signals from the suprachiasmatic Nucleus (SCN), the site of a dominant circadian pacemaker. Various lines of evidence indicate that arginine-vasopressin (AVP)-containing projections from the SCN to the preoptic area (POA) contribute to the production of the surge of LH-releasing hormone (LHRH). These actions may be mediated by V1a because the transcript for this AVP receptor subtype is predominant within the POA of the female rat. In this study, in situ hybridization histochemistry was used to examine V1a mRNA expression, either by itself or together with LHRH or glutamic acid decarboxylase 65 (GAD65) mRNA, within the POA of ovariectomized rats in the presence or absence of oestrogen. V1a mRNA was found in cells across the rostro-caudal axis of the POA; some were in close proximity to cells expressing LHRH mRNA. Coexpression of V1a and LHRH mRNAs was detected only very rarely. By contrast, cells with V1a mRNA commonly displayed GAD65 mRNA. The density of V1a mRNA-expressing cells was particularly high within the anteroventral Periventricular Nucleus; at this site, V1a mRNA expression was elevated following oestrogen treatment. The present results indicate that V1a-mediated AVP actions may influence LHRH release via cells in the immediate vicinity of LHRH neurones and/or via oestrogen-regulated cells in the anteroventral Periventricular Nucleus, which is a site that lacks LHRH neurones but plays an essential role in initiating the preovulatory LH surge.
Sandra L Petersen - One of the best experts on this subject based on the ideXlab platform.
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developmental exposure to 2 3 7 8 tetrachlorodibenzo p dioxin may alter lh release patterns by abolishing sex differences in gaba glutamate cell number and modifying the transcriptome of the male anteroventral Periventricular Nucleus
Neuroscience, 2016Co-Authors: Javier Del Pino Sans, Kelsey J Clements, Alexander Suvorov, Sudha Krishnan, Hillary Adams, Sandra L PetersenAbstract:Developmental exposure to arylhydrocarbon receptor (AhR) ligands abolishes sex differences in a wide range of neural structures and functions. A well-studied example is the anteroventral Periventricular Nucleus (AVPV), a structure that controls sex-specific luteinizing hormone (LH) release. In the male, testosterone (T) secreted by the developing testes defeminizes LH release mechanisms; conversely, perinatal AhR activation by 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) blocks defeminization. To better understand developmental mechanisms altered by TCDD exposure, we first verified that neonatal TCDD exposure in male rats prevented the loss of AVPV GABA/glutamate neurons that are critical for female-typical LH surge release. We then used whole genome arrays and quantitative real-time polymerase chain reaction (QPCR) to compare AVPV transcriptomes of males treated neonatally with TCDD or vehicle. Our bioinformatics analyses showed that TCDD enriched gene sets important for neuron development, synaptic transmission, ion homeostasis, and cholesterol biosynthesis. In addition, upstream regulatory analysis suggests that both estrogen receptors (ER) and androgen receptors (AR) regulate genes targeted by TCDD. Of the 23 mRNAs found to be changed by TCDD at least 2-fold (p<0.05), most participate in the functions identified in our bioinformatics analyses. Several, including matrix metallopeptidase 9 and SRY-box 11 (Sox11), are known targets of E2. CUG triplet repeat, RNA binding protein 2 (cugbp2) is particularly interesting because it is sex-specific, oppositely regulated by estradiol (E2) and TCDD. Moreover, it regulates the post-transcriptional processing of molecules previously linked to sexual differentiation of the brain. These findings provide new insights into how TCDD may interfere with defeminization of LH release patterns.
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17β estradiol and progesterone regulate multiple progestin signaling molecules in the anteroventral Periventricular Nucleus ventromedial Nucleus and sexually dimorphic Nucleus of the preoptic area in female rats
Neuroscience, 2011Co-Authors: Karlie A Intlekofer, Sandra L PetersenAbstract:Recent work identified novel progestin signaling molecules, including progesterone receptor membrane component 1 (Pgrmc1), Pgrmc2, serpine mRNA binding protein 1 (Serbp1), progestin and adiponectin receptors 7 (Paqr7) and Paqr8. These molecules mediate rapid progesterone (P(4)) effects in non-neural tissue and we recently mapped their expression in the brain. Many rapid effects of P(4) require 17β-estradiol (E(2)) and P(4) priming; therefore, we examined the effects of ovarian hormones on the expression of these non-classical progestin signaling molecules. We focused specifically on the anteroventral Periventricular Nucleus (AVPV), the sexually dimorphic Nucleus of the preoptic area (SDN-POA) and the ventrolateral portion of the ventromedial Nucleus (VMNvl). These brain nuclei are important for female reproduction. Ovariectomized adult female rats were implanted with capsules containing sesame oil or E(2), and injected 48 h later with sesame oil or P(4). Brains were collected 8 h later and RNA was isolated from the AVPV, SDN-POA and VMNvl. We assessed the effects of ovarian hormones on mRNA levels using quantitative polymerase chain reaction (QPCR). In the AVPV, Serbp1 mRNA levels were increased by P(4) in the presence of E(2), and Paqr8 was downregulated by P(4) alone. In the SDN-POA, combined E(2) and P(4) increased Pgrmc1 and Serbp1 mRNA levels, and E(2) alone increased Paqr8 mRNA levels. Finally, in the VMNvl, P(4) increased mRNA levels encoding Pgrmc1, Pgrmc2 and Serbp1, and the combination of E(2) and P(4) increased Pgrmc1 and Serbp1 mRNA levels. Paqr7 was not regulated by E(2) or P(4) in any brain region examined. In summary, we showed that ovarian hormones regulate novel progestin signaling molecules in brain regions important for the neuroendocrine control of reproduction.
Shinji Hayashi - One of the best experts on this subject based on the ideXlab platform.
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sexually dimorphic expression of estrogen receptor β in the anteroventral Periventricular Nucleus of the rat preoptic area implication in luteinizing hormone surge
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Chitose Orikasa, Yasuhiko Kondo, Shinji Hayashi, Bruce S Mcewen, Yasuo SakumaAbstract:Striking sex difference was detected in the expression of estrogen receptor (ER) β mRNA and protein by nonisotopic in situ hybridization and immunohistochemistry in the anteroventral Periventricular Nucleus (AVPV) of the rat preoptic area. In females more than in males, a significantly larger number of ERβ mRNA-positive cells were visualized in the medial-most portion of the AVPV within 50 μm from the ependymal lining of the third ventricle. Rats of 7, 14, 21, 35, and 60 days of age (d 1 = day of birth) showed the sex difference. Orchidectomy of male neonates or estrogen treatment of female pups reversed the brain phenotype when examined on d 14. In the AVPV of adult females, ERα immunoreactivity colocalized in 83% of ERβ mRNA-positive cells. Tyrosine hydroxylase immunoreactivity colocalized in 18% of ERβ immunoreactive cells in d 21 females. Infusion of an ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. These findings provide support for the hypothesis that activation of ERβ in the AVPV is an important regulatory event in the female-typical induction of luteinizing hormone surge by estrogen.
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postnatal development and sex difference in neurons containing estrogen receptor alpha immunoreactivity in the preoptic brain the diencephalon and the amygdala in the rat
The Journal of Comparative Neurology, 1997Co-Authors: Makoto Yokosuka, Hiroaki Okamura, Shinji HayashiAbstract:Estrogen has been considered as a key substance that induces sexual differentiation of the brain during fetal and neonatal life in the rat. Thus, to define the brain regions involved in the brain sexual differentiation, we examined the regions where the estrogen receptor (ER) is located in the developing rat brain. We examined immunohistochemical distribution of the cells containing estrogen receptor-α (ER-α) in the preoptic region, the diencephalon, and the amygdala in male and female rats on postnatal days 1–35 (PD1–PD35). The antibody used recognizes ER-α equally well for both occupied and unoccupied forms. ER-α immunostaining was restricted to the cell nuclei of specific cell groups. In PD1 rats, ER-α-immunoreactive (ER-IR) signals were detected in the lateral septum, the organum vasculosum lamina terminalis, the medial preoptic Nucleus (MPN), the median preoptic Nucleus, the bed Nucleus of the stria terminalis, the hypothalamic Periventricular Nucleus, the lateral habenula, the posterodorsal part of the medial amygdala Nucleus, the posterior part of the cortical amygdala Nucleus, the hypothalamic ventromedial Nucleus (VMH), the hypothalamic arcuate Nucleus, and the posterior hypothalamic Periventricular Nucleus. The distribution pattern of ER-IR cells in the newborn rat was much the same as that in the adult in the preoptic-hypothalamic and amygdala regions. Moreover, the signals in the MPN and the VMH were stronger in the female than in the male, perhaps reflecting the ability of estrogen generated by aromatization of testosterone in the male to down-regulate the ER signal. Thus, the brain regions showing sex differences may be sites of sexual differentiation of the brain by aromatizable androgen during the neonatal period. J. Comp. Neurol. 389:81–93, 1997. © 1997 Wiley-Liss, Inc.
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induction of substance p immunoreactivity by estrogen in neurons containing estrogen receptors in the anterovental Periventricular Nucleus of female but not male rats
Journal of Neuroendocrinology, 1994Co-Authors: Hiroaki Okamura, Makoto Yokosuka, Shinji HayashiAbstract:Effects of gonadal steroids on numbers of neurons containing estrogen receptor (ER) and/or substance P (SP) were examined in the anteroventral Periventricular Nucleus (AVPV) of female and male rats by double-labeling immunohistochemistry employing antibodies specific for ER and SP. Animals were gonadectomized and received subcutaneously either oil alone (Control group), sequential injections of estradiol benzoate and oil (EB + Oil group), or those of EB and progesterone (EB + P group). In the female control rat, a large population of ER-immunoreactive (IR) cells were found clustered throughout the AVPV. They were counted more than 2,000 in total of 4 sections in this Nucleus. On the contrary, SP-IR neurons were scarcely observed in the same area of this group. Administration of estrogen to female animals decreased the total number of ER-IR cells to 67% of the control group. In contrast to the supressive effect of estrogen to its own receptor, it induced SP-IR neurons in the AVPV of the female. Approximately 50–80 SP-IR neurons were counted in the 4 sections, and 59% of these neurons expressed ER-IR material in their nuclei. In the female EB + P group, the number of ER-IR neurons also decreased to 79% of the control group. Although the number of SP-IR neurons in this group decreased to 32% of that in the EB + Oil group, a ratio of coexistence of ER-IR material in these neurons increased to 75%. The male control group contained a smaller population of ER-IR cells relative to the female control (1497 vs 2143). SP-IR neurons were rarely observed as were in the female control. Administration of estrogen to the male also decreased the number of ER-IR cells in a manner similar to that in the female. However, unlike the female, the steroid failed to induce the SP-IR neurons in the male. These results demonstrate sexual dimorphism in the AVPV not only in the number of ER-IR neurons but also in the responsiveness of SP neurons to estrogen. They further provide anatomical evidence that a subset of SP neurons are regulated by estradiol in estrogen sensitive neurons in the female rat. The data also suggest that this peptide is involved in mechanisms of luteinizing hormone surge by mediating actions of gonadal steroids in the AVPV.