scholarly journals Overexpression of Corticotropin Releasing Factor in the Central Nucleus of the Amygdala Advances Puberty and Disrupts Reproductive Cycles in Female Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3934-3944 ◽  
Author(s):  
X. F. Li ◽  
M. H. Hu ◽  
S. Y. Li ◽  
C. Geach ◽  
A. Hikima ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Pulse Generator ◽  
Female Rats ◽  
Central Nucleus ◽  
Ovariectomized Rats ◽  
Human Society ◽  
Central Administration ◽  
Corticosterone Secretion ◽  
Stress Changes

Abstract Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal axis. Because CRF expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic GnRH pulse generator, we tested the hypothesis that overexpression of CRF in the CeA of female rats alters anxiety behavior, dysregulates the HPA axis response to stress, changes pubertal timing, and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of preweaning (postnatal day 12) female rats. Overexpression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats overexpressing CRF. Despite the absence of change in basal corticosterone secretion or induced by stress (lipopolysaccharide or restraint), overexpression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in postpubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.

scholarly journals The Role of the Medial and Central Amygdala in Stress-Induced Suppression of Pulsatile LH Secretion in Female Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (2) ◽  
pp. 545-555 ◽  
Author(s):  
Yuanshao Lin ◽  
Xiaofeng Li ◽  
Micol Lupi ◽  
James S. Kinsey-Jones ◽  
Bei Shao ◽  
...  
Keyword(s):  
Pulse Generator ◽  
Reproductive Function ◽  
Ibotenic Acid ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Inhibitory Effects ◽  
Cardiac Catheters ◽  
Response To Stress ◽  
Lh Secretion

Abstract Stress exerts profound inhibitory effects on reproductive function by suppressing the pulsatile release of GnRH and therefore LH. Although the mechanisms by which stressors disrupt the hypothalamic GnRH pulse generator remain to be fully elucidated, numerous studies have implicated the amygdala, especially its medial (MeA) and central nuclei (CeA), as key modulators of the neuroendocrine response to stress. In the present study, we investigated the roles of the MeA and CeA in stress-induced suppression of LH pulses. Ovariectomized rats received bilateral ibotenic acid or sham lesions targeting the MeA or CeA; blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for the measurement of LH pulses. After 2 h of baseline sampling, the rats were exposed to either: restraint (1 h), insulin-induced hypoglycemia (IIH) (0.3 U/kg, iv), or lipopolysaccharide (LPS) (25 μg/kg, iv) stress. The restraint but not IIH or LPS stress–induced suppression of LH pulses was markedly attenuated by the MeA lesions. In contrast, CeA lesioning attenuated LPS, but not restraint or IIH stress–induced suppression of LH pulses. Moreover, after restraint stress, the number of Fos-positive neurons and the percentage of glutamic acid decarboxylase67 neurons expressing Fos was significantly greater in the GnRH-rich medial preoptic area (mPOA) of rats with intact, rather than lesioned, MeA. These data indicate that the MeA and CeA play key roles in psychogenic and immunological stress-induced suppression of the GnRH pulse generator, respectively, and the MeA-mediated effect may involve γ-aminobutyric acid ergic signaling within the mPOA.

scholarly journals Effect of vasopressin 1b receptor blockade on the hypothalamic–pituitary–adrenal response of chronically stressed rats to a heterotypic stressor

2008 ◽  
Vol 200 (3) ◽  
pp. 285-291 ◽  
Author(s):  
Francesca Spiga ◽  
Louise R Harrison ◽  
Cliona P MacSweeney ◽  
Fiona J Thomson ◽  
Mark Craighead ◽  
...  
Keyword(s):  
White Noise ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Home Cage ◽  
Male Rats ◽  
Receptor Blockade ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosterone Secretion ◽  
Corticosterone Response ◽  
Adrenal Response

Exposure to chronic restraint (CR) modifies the hypothalamic–pituitary–adrenal (HPA) axis response to subsequent acute stressors with adaptation of the response to a homotypic and sensitization of the response to a heterotypic stressor. Since vasopressin (AVP) activity has been reported to change during chronic stress, we investigated whether this was an important factor in HPA facilitation. We therefore tested whether vasopressin 1b receptor (AVPR1B) blockade altered the ACTH and corticosterone response to heterotypic stressors following CR stress. Adult male rats were exposed to CR, single restraint, or were left undisturbed in the home cage. Twenty-four hours after the last restraint, rats were injected with either a AVPR1B antagonist (Org, 30 mg/kg, s.c.) or vehicle (5% mulgofen in saline, 0.2/kg, s.c.) and then exposed to either restraint, lipopolysaccharide (LPS) or white noise. CR resulted in the adaptation of the ACTH and corticosterone response to restraint and this effect was not prevented by pretreatment with Org. Although we found no effect of CR on LPS-induced ACTH and corticosterone secretion, both repeated and single episodes of restraint induced the sensitization of the ACTH, but not corticosterone response to acute noise. Pretreatment with Org reduced the exaggerated ACTH response to noise after both single and repeated exposure to restraint.

scholarly journals Intrahypothalamic Estradiol Modulates Hypothalamus-Pituitary-Adrenal-Axis Activity in Female Rats

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3337-3344 ◽  
Author(s):  
J. Liu ◽  
P. H. Bisschop ◽  
L. Eggels ◽  
E. Foppen ◽  
E. Fliers ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Restraint Stress ◽  
Acute Stress ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Stress Exposure ◽  
Ici 182,780 ◽  
Hpa Axis Activity

Estrogen plays an important role in the regulation of the hypothalamus-pituitary-adrenal (HPA)-axis, but the neuroendocrine pathways and the role of estrogen receptor (ER) subtypes involved in specific aspects of this interaction remain unknown. In a first set of experiments, we administered estradiol (E2) intravenously, intracerebroventricularly, and by intrahypothalamic microdialysis to ovariectomized rats to measure plasma corticosterone (CORT) concentrations from carotid artery blood. Systemic infusion of E2 did not increase plasma CORT, but intracerebroventricular E2 induced a 3-fold CORT increase (P = 0.012). Local E2 infusions in the hypothalamic paraventricular nucleus (PVN) significantly increased plasma CORT (P < 0.001). A similar CORT increase was seen after PVN infusion of the ERα agonist propylpyrazoletriol, whereas the ERβ agonist diarylpropiolnitrile had no effect. In a second set of experiments, we investigated whether E2 modulates the HPA-axis response to acute stress by administering E2 agonists or its antagonist ICI 182,780 into the PVN during restraint stress exposure. After 30 min of stress exposure, plasma CORT had increased 5.0-fold (P < 0.001). E2 and propylpyrazoletriol administration in the PVN enhanced the stress-induced plasma CORT increase (8-fold vs. baseline), whereas ICI 182,780 and diarylpropiolnitrile reduced it, as compared with both E2 and vehicle administration in the PVN. In conclusion, central E2 modulates HPA-axis activity both in the basal state and during restraint stress. In the basal condition, the stimulation is mediated by ERα-sensitive neurons, whereas during stress, it is mediated by both ERα and ERβ.

scholarly journals SAT-451 Chronic Stress During Adolescence of Rats Shows Sex Dimorphism in the Thyroid Axis Response to Voluntary Exercise in Adulthood

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Marco Antonio Parra-Montes de Oca ◽  
Angélica Gutiérrez-Mata ◽  
Jean-Louis Charli ◽  
Patricia Joseph-Bravo
Keyword(s):  
Thyroid Hormones ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Dependent Manner ◽  
Target Organs ◽  
Brown Adipose ◽  
Hpt Axis ◽  
Response To Exercise

Abstract Exposure to chronic stress during adolescence causes long-term effects on the response of Hypothalamus-Pituitary-Adrenal (HPA) axis, affecting behavior and energy homeostasis. Voluntary exercise activates the HP-Thyroid (HPT) axis allowing efficient fluxes of substrates to active target organs. Chronic stress in adult rats blunts HPT axis response to voluntary exercise in a sex-dependent manner (Front Endocrinol 10(418):1-13, 2019). As adolescents show sex-dependent responses to stress, we sought to evaluate the effect of chronic stress at this period in the response of HPT axis to voluntary exercise in adulthood. Wistar male and female rats were divided in an undisturbed group (Control, C) and one group exposed to chronic variable stress (CVS) where the rats were daily subjected to different stressors during postnatal day (PND) 30 to 60 for females and PND 30 to 70 for males. At adulthood (PND 74 for females and PND 84 for males) rats were exposed to running wheel following published protocol (Endocrinology 155:2020-2030, 2014). As females are more susceptible to stress during adolescence than males, additional independent experiments were performed with female rats kept in group or individual housing, since PND 30 (2 per cage or isolated (Iso)). At PND 64, Iso rats were housed in pairs and exposed to CVS every 3 days until PND 80; later, rats were exercised 26 days. Hormones were quantified by ELISA or RIA; mRNA expression was determined by RT-PCR. Voluntary exercise reduced fat mass in C groups, dependent on the amount of exercise performed; stressed rats exercised did not lose fat, indicating that adolescent stress avoids an appropriate energy distribution during exercise. The expression of Crh and Avp in hypothalamic paraventricular nucleus (PVN) decreased in stressed groups mainly in females, as reported. Exercise decreased corticosterone levels only in C rats, suggesting that CVS during adolescence modifies the HPA axis response to exercise. CVS inhibited Pomc expression induced by exercise and increased Npy expression in arcuate nucleus, decreased Trh expression in PVN for both sexes and in dorsomedial hypothalamus in males. Thyroid hormones were not altered in CVS males and Iso females; however, T3 and T4 levels were high in CVS females, so different stress exposures may modify the HPT axis state in females. The response to exercise of the target organs of thyroid hormones reveals with more accuracy the activity of HPT axis, exercise stimulated the expression of Adrb3 and Dio2 in brown adipose tissue of C females, and the expression of Dio2 and Pgc1a in skeletal muscle (gastrocnemius) of both sexes, changes attenuated by CVS. These results indicate that chronic stress during adolescence blunts the response of HPT axis to voluntary exercise, strongly in females than males.

Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats

2002 ◽  
Vol 283 (6) ◽  
pp. R1378-R1385 ◽  
Author(s):  
Lisa A. Eckel ◽  
Thomas A. Houpt ◽  
Nori Geary
Keyword(s):  
Food Intake ◽  
Area Postrema ◽  
Body Weight Gain ◽  
Meal Size ◽  
Female Rats ◽  
Central Nucleus ◽  
Ovariectomized Rats ◽  
Estradiol Treatment ◽  
Central Processing ◽  
Fos Expression

The ovarian hormone estradiol reduces meal size and food intake in female rats, at least in part by increasing the satiating potency of CCK. Here we used c-Fos immunohistochemistry to determine whether estradiol increases CCK-induced neuronal activation in several brain regions implicated in the control of feeding. Because the adiposity signals leptin and insulin appear to control feeding in part by increasing the satiating potency of CCK, we also examined whether increased adiposity after ovariectomy influences estradiol's effects on CCK-induced c-Fos expression. Ovariectomized rats were injected subcutaneously with 10 μg 17β-estradiol benzoate (estradiol) or vehicle once each on Monday and Tuesday for 1 wk ( experiment 1) or for 5 wk ( experiment 2). Two days after the final injection of estradiol or vehicle, rats were injected intraperitoneally with 4 μg/kg CCK in 1 ml/kg 0.9 M NaCl or with vehicle alone. Rats were perfused 60 min later, and brain tissue was collected and processed for c-Fos immunoreactivity. CCK induced c-Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus of the hypothalamus (PVN), and central nucleus of the amygdala (CeA) in vehicle- and estradiol-treated ovariectomized rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, the PVN, and the CeA, but not in the rostral NTS or AP. This action of estradiol was very similar in rats tested before ( experiment 1) and after ( experiment 2) significant body weight gain, suggesting that adiposity does not modulate CCK-induced c-Fos expression or interact with estradiol's ability to modulate CCK-induced c-Fos expression. These findings suggest that estradiol inhibits meal size and food intake by increasing the central processing of the vagal CCK satiation signal.

An Enriched Environment Reduces Chronic Stress-Induced Visceral Pain Through Modulating Microglial Activity in the Central Nucleus of the Amygdala

2021 ◽  
Author(s):  
Tian Yuan ◽  
Albert Orock ◽  
Beverley Greenwood-Van Meerveld
Keyword(s):  
Chronic Stress ◽  
Environmental Enrichment ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Female Rats ◽  
Central Nucleus ◽  
Dorsal Margin ◽  
Protective Effects ◽  
Male And Female Rats ◽  
Synaptic Pruning

Cognitive behavioral therapy (CBT) improves the quality of life for patients with brain-gut disorders, however, the underlying mechanisms of CBT remain to be explored. Previously we showed that environmental enrichment (EE), an experimental paradigm that mirrors positive behavioral intervention, ameliorates chronic stress-induced visceral hypersensitivity in a rodent model via mechanisms involving altered activity in the central nucleus of amygdala (CeA). In the present study, we investigated whether microglia-mediated synaptic plasticity in the CeA is a potential mechanism underlying the protective effects of EE against stress-induced visceral hypersensitivity. We sterotaxically implanted corticosterone (CORT) micropellets onto the dorsal margin of the CeA shown previously to induce colonic hypersensitivity. Animals were housed in EE cages or standard cages for 14 days following CORT implantation. Visceral sensitivity was assessed via visceromotor behavioral response to colorectal distension. Microglial morphology, microglia-mediated synaptic engulfment and the expression of synaptic pruning-related signals C1q, C3 and C3R were measured using immunofluorescence and RNAscope assay. We found that housing CORT implanted rats in EE cages for 14 days attenuated visceral hypersensitivity in both male and female rats as compared to control rats maintained in standard housing. EE reduced CORT-induced microglial remodeling and microglia-mediated synaptic pruning with reduced C1q and CR3, but not C3, expression. Our data suggest that exposure to EE is sufficient to ameliorate stress-induced visceral pain via reducing amygdala microglia-modulated neuronal plasticity.

Paraventricular Dynorphin A Neurons Mediate LH Pulse Suppression Induced by Hindbrain Glucoprivation in Female Rats

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Hitomi Tsuchida ◽  
Parvin Mostari ◽  
Koki Yamada ◽  
Sae Miyazaki ◽  
Yuki Enomoto ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Critical Role ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Central Administration ◽  
Dynorphin A ◽  
Gonadotropin Secretion ◽  
Feedback Level ◽  
Estradiol 17Β

Abstract Malnutrition suppresses reproductive functions in mammals, which is considered to be mostly due to the inhibition of pulsatile gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC) play a critical role in the regulation of pulsatile GnRH/gonadotropin release. The present study aimed to examine if the hypothalamic dynorphin A (Dyn) neurons mediate the suppression of GnRH/luteinizing hormone (LH) pulses during malnutrition. Ovariectomized rats treated with a negative feedback level of estradiol-17β-treated (OVX+E2) were administered with intravenous (iv) or fourth cerebroventricle (4V) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, to serve as a malnutrition model. Central administration of a Dyn receptor antagonist blocked the iv- or 4V-2DG-induced suppression of LH pulses in OVX+E2 rats. The 4V 2DG administration significantly increased the number of Pdyn (Dyn gene)-positive cells co-expressing fos in the paraventricular nucleus (PVN), but not in the ARC and supraoptic nucleus (SON), and the iv 2DG treatment significantly increased the number of fos and Pdyn-co-expressing cells in the PVN and SON, but decreased it in the ARC. The E2 treatment significantly increased Pdyn expression in the PVN, but not in the ARC and SON. Double in situ hybridization for Kiss1 (kisspeptin gene) and Oprk1 (Dyn receptor gene) revealed that around 60% of ARC Kiss1-expressing cells co-expressed Oprk1. These results suggest that the PVN Dyn neurons, at least in part, mediate LH pulse suppression induced by the hindbrain or peripheral glucoprivation, and Dyn neurons may directly suppress the ARC kisspeptin neurons in female rats.

scholarly journals The Role of the Forebrain Glucocorticoid Receptor in Acute and Chronic Stress

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5482-5490 ◽  
Author(s):  
Amy R. Furay ◽  
Amy E. Bruestle ◽  
James P. Herman
Keyword(s):  
Glucocorticoid Receptor ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Basolateral Amygdala ◽  
Feedback Regulation ◽  
Negative Feedback Regulation ◽  
Acute And Chronic Stress ◽  
Corticosterone Secretion

Previous work has implicated the forebrain glucocorticoid receptor (GR) in feedback regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present series of experiments used male mice with a targeted forebrain-specific GR knockout (in which forebrain includes the prefrontal cortex, hippocampus, and basolateral amygdala) to determine the role of forebrain GR in HPA axis regulation after stress. The data indicate that the forebrain GR is necessary for maintaining basal regulation of corticosterone secretion in the morning, confirming its role in HPA axis regulation. Our data further indicate that the forebrain GR is necessary for negative feedback after both mild and robust acute psychogenic stressors but not hypoxia, a systemic stressor. In contrast, forebrain-specific GR knockout and control mice exhibit equivalent HPA axis hyperactivity and facilitation after chronic variable stress, suggesting that changes in forebrain GR are not essential for chronic stress-induced pathology. These studies provide novel and definitive evidence that the forebrain GR selectively contributes negative feedback regulation of HPA axis responses to psychogenic stressors. Moreover, the data indicate that chronic stress-induced alterations in HPA axis function are mediated by mechanisms independent of the forebrain GR. Overall, the data are consistent with an essential role of the forebrain GR in coordinating endocrine responses to stimuli of a psychological origin.

scholarly journals CRF-R1 Antagonist Treatment Exacerbates Circadian Corticosterone Secretion under Chronic Stress, but Preserves HPA Feedback Sensitivity

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2114
Author(s):  
Yadira Ibarguen-Vargas ◽  
Samuel Leman ◽  
Rupert Palme ◽  
Catherine Belzung ◽  
Alexandre Surget
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Negative Feedback ◽  
Chronic Mild Stress ◽  
Stress Conditions ◽  
Mild Stress ◽  
Circadian Activity ◽  
Corticosterone Secretion ◽  
Feedback Sensitivity ◽  
The Impact

Despite promising initial reports, corticotropin-releasing factor receptor type-1 (CRF-R1) antagonists have mostly failed to display efficacy in clinical trials for anxiety or depression. Rather than broad-spectrum antidepressant/anxiolytic-like drugs, they may represent an ‘antistress’ solution for single stressful situations or for patients with chronic stress conditions. However, the impact of prolonged CRF-R1 antagonist treatments on the hypothalamic–pituitary–adrenal (HPA) axis under chronic stress conditions remained to be characterized. Hence, our study investigated whether a chronic CRF-R1 antagonist (crinecerfont, formerly known as SSR125543, 20 mg·kg−1·day−1 ip, 5 weeks) would alter HPA axis basal circadian activity and negative feedback sensitivity in mice exposed to either control or chronic stress conditions (unpredictable chronic mild stress, UCMS, 7 weeks), through measures of fecal corticosterone metabolites, plasma corticosterone, and dexamethasone suppression test. Despite preserving HPA axis parameters in control non-stressed mice, the 5-week crinercerfont treatment improved the negative feedback sensitivity in chronically stressed mice, but paradoxically exacerbated their basal corticosterone secretion nearly all along the circadian cycle. The capacity of chronic CRF-R1 antagonists to improve the HPA negative feedback in UCMS argues in favor of a potential therapeutic benefit against stress-related conditions. However, the treatment-related overactivation of HPA circadian activity in UCMS raise questions about possible physiological outcomes with long-standing treatments under ongoing chronic stress.

scholarly journals The Role of the Locus Coeruleus in Corticotropin-Releasing Hormone and Stress-Induced Suppression of Pulsatile Luteinizing Hormone Secretion in the Female Rat

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 323-331 ◽  
Author(s):  
J. C. Mitchell ◽  
X. F. Li ◽  
L. Breen ◽  
J.-C. Thalabard ◽  
K. T. O’Byrne
Keyword(s):  
Glutamic Acid ◽  
Locus Coeruleus ◽  
Stress Responses ◽  
Pulse Generator ◽  
Critical Role ◽  
Ovariectomized Rats ◽  
Female Rat ◽  
Central Administration ◽  
17Β Estradiol ◽  
Lh Secretion

Despite a wealth of evidence for CRH mediating stress-induced suppression of the hypothalamic GnRH pulse generator, and hence reproductive dysfunction, the site and mechanism of action remains elusive. The locus coeruleus (LC), a prominent noradrenergic brain stem nucleus, is innervated by CRH neurons, mediates several behavioral stress responses, and is implicated in the control of pulsatile LH secretion. The aim of this study was to test the hypothesis that LC CRH has a critical role in mediating stress-induced suppression of pulsatile LH secretion in the rat. Ovariectomized rats with 17β-estradiol or oil-filled sc capsules were implanted with bilateral LC and iv cannulae. Central administration of CRH (10 ng to 1 μg) resulted in a dose-dependent suppression of LH pulses, which was reversed by a CRH receptor antagonist (α-helical CRF9–41, 1 μg). The induction of c-fos expression in glutamic acid decarboxylase67 immunostained neurons in the preoptic area suggests activation of the secretion of γ-aminobutyric acid in response to intracoerulear administration of CRH; 17β-estradiol further increased the percentage of glutamic acid decarboxylase67-positive neurons that expressed fos and augmented suppression of LH pulses. Furthermore, intracoerulear administration of α-helical CRF9–41 completely blocked restraint stress-induced suppression of LH pulses, without affecting the inhibitory response to hypoglycemia. These results suggest that CRH innervation of the LC may play a pivotal, but differential, role in the normal physiological response of stress-induced suppression of the GnRH pulse generator and hence the reproductive system.

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