scholarly journals Stress-induced inhibition of LH pulses in female rats: role of GABA in arcuate nucleus

2015 ◽  
Vol 55 (1) ◽  
pp. 9-19 ◽  
Author(s):  
XiaoFeng Li ◽  
Bei Shao ◽  
ChengCheng Lin ◽  
Kevin T O'Byrne ◽  
YuanShao Lin
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Reproductive Function ◽  
Pulse Frequency ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Inhibitory Effects ◽  
Corticotrophin Releasing Factor ◽  
Cgp 35348

Stress exerts profound inhibitory effects on reproductive function by suppression of the pulsatile release of GnRH and therefore LH. Besides the corticotrophin-releasing factor (CRF), this effect also might be mediated via GABAergic signaling within the arcuate nucleus (ARC) since its inhibitory effects on LH pulses and increased activity during stress. In the present study, we investigated the role of endogenous GABAergic signaling within the ARC in stress-induced suppression of LH pulses. Ovariectomised oestradiol-replaced rats were implanted with bilateral and unilateral cannulae targeting toward the ARC and lateral cerebral ventricle respectively. Blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for measurement of LH pulses. Intra-ARC infusion of GABAAreceptor antagonist, bicuculline (0.2 pmol in 200 nl artificial cerebrospinal fluid (aCSF) each side, three times at 20-min intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS; 25 μg/kg i.v.) but not restraint (1 h) stress on pulsatile LH secretion. In contrast, restraint but not LPS stress-induced suppression of LH pulse frequency was reversed by intra-ARC administration of GABABR antagonist, CGP-35348 (1.5 nmol in 200 nl aCSF each side, three times at 20-min intervals). Moreover, intra-ARC application of either bicuculline or CGP-35348 attenuated the inhibitory effect of CRF (1 nmol in 4 μl aCSF, i.c.v.) on the LH pulses. These data indicate a pivotal and differential role of endogenous GABAAand GABABsignaling mechanisms in the ARC with respect to mediating immunological and psychological stress-induced suppression of the GnRH pulse generator respectively.

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 Arcuate nucleus kisspeptin response to increased nutrition in rams

2019 ◽  
Vol 31 (11) ◽  
pp. 1682 ◽  
Author(s):  
S. E. Rietema ◽  
P. A. R. Hawken ◽  
C. J. Scott ◽  
M. N. Lehman ◽  
G. B. Martin ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Nutritional Supplementation ◽  
Environmental Cues ◽  
Dorsomedial Hypothalamus ◽  
Gonadotrophin Releasing Hormone ◽  
Kndy Neurons

Rams respond to acute nutritional supplementation by increasing the frequency of gonadotrophin-releasing hormone (GnRH) pulses. Kisspeptin neurons may mediate the effect of environmental cues on GnRH secretion, so we tested whether the ram response to nutrition involves activation of kisspeptin neurons in the arcuate nucleus (ARC), namely kisspeptin, neurokin B, dynorphin (KNDy) neurons. Rams were given extra lupin grain with their normal ration. Blood was sampled before feeding, and continued until animals were killed for collection of brain tissue at 2 or 11h after supplementation. In supplemented rams, LH pulse frequency increased after feeding, whereas control animals showed no change. Within the caudal ARC, there were more kisspeptin neurons in supplemented rams than in controls and a higher proportion of kisspeptin cells coexpressed Fos, regardless of the time the rams were killed. There were more Fos cells in the mid-ARC and mid-dorsomedial hypothalamus of the supplemented compared with control rams. No effect of nutrition was found on kisspeptin expression in the rostral or mid-ARC, or on GnRH expression in the preoptic area. Kisspeptin neurons in the caudal ARC appear to mediate the increase in GnRH and LH production due to acute nutritional supplementation, supporting the hypothesised role of the KNDy neurons as the pulse generator for GnRH.

scholarly journals Relative Importance of the Arcuate and Anteroventral Periventricular Kisspeptin Neurons in Control of Puberty and Reproductive Function in Female Rats

Endocrinology ◽  
2015 ◽  
Vol 156 (7) ◽  
pp. 2619-2631 ◽  
Author(s):  
M. H. Hu ◽  
X. F. Li ◽  
B. McCausland ◽  
S. Y. Li ◽  
R. Gresham ◽  
...  
Keyword(s):  
Pubertal Timing ◽  
Critical Role ◽  
Reproductive Function ◽  
Pulse Frequency ◽  
Pulse Generation ◽  
Female Rats ◽  
Relative Importance ◽  
Lh Surge ◽  
Estrous Cyclicity

Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.

scholarly journals Reversal of the hypothalamo-pituitary–adrenal response to oestrogens around puberty

2009 ◽  
Vol 202 (2) ◽  
pp. 279-285 ◽  
Author(s):  
Obaro Evuarherhe ◽  
James Leggett ◽  
Eleanor Waite ◽  
Yvonne Kershaw ◽  
Stafford Lightman
Keyword(s):  
Corticosterone Level ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Female Rats ◽  
Inhibitory Effects ◽  
Sampling System ◽  
Gender Dimorphism ◽  
Adrenal Response ◽  
Hpa Axis Activity

The neuroendocrine gender dimorphism that begins during perinatal development is completed during puberty. We have previously described how the perinatal gonadal steroids programme hypothalamic–pituitary–adrenal (HPA) activity in adulthood and we now assess the role of peripubertal ovarian hormones. Prepubertal females were treated subcutaneously with either cholesterol or 17β-oestradiol and their pituitary–adrenal activity was assessed 5 days later. Oestradiol suppressed the ACTH and corticosterone responses to restraint stress in the prepubertal female. Furthermore, groups of female rats were ovariectomised (OVX) either before or after puberty and adult animals were subsequently treated with subcutaneous implants containing either 17β-oestradiol or cholesterol. Corticosterone pulsatility was assessed using an automated blood sampling system to collect blood from freely moving animals at 10 min intervals over 24 h. Oestradiol administered to adults that had been OVX either pre- or post-pubertally displayed a significantly higher mean corticosterone level as well as increased pulse frequency and pulse amplitude compared with cholesterol treated controls. These data demonstrate a reversal in the effect of oestrogens on HPA axis activity over the time of puberty with inhibitory effects prepubertally and stimulatory actions after puberty and imply an ovarian steroid-independent mechanism of pubertal maturation of HPA sensitivity to oestrogens.

scholarly journals Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 493
Author(s):  
 Chung-Yu Chen ◽  
Chien-Rung Chen ◽  
Chiao-Nan Chen ◽  
Paulus S. Wang ◽  
Toby Mündel ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Prostaglandin F2α ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Steroidogenic Enzyme ◽  
Estradiol Secretion ◽  
Basal Release ◽  
Ca2 Channels

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females.

scholarly journals Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3071 ◽  
Author(s):  
Giustino Orlando ◽  
Sheila Leone ◽  
Claudio Ferrante ◽  
Annalisa Chiavaroli ◽  
Adriano Mollica ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Inhibitory Effect ◽  
Bdnf Gene ◽  
Appetite Control ◽  
Hydroxyindoleacetic Acid ◽  
Puberty Onset

Besides its role as key regulator in gonadotropin releasing hormone secretion, reproductive function, and puberty onset, kisspeptin has been proposed to act as a bridge between energy homeostasis and reproduction. In the present study, to characterize the role of hypothalamic kisspeptin as metabolic regulator, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIIA) concentrations in rat hypothalamic (Hypo-E22) cells. Our study showed that kisspeptin-10 in the concentration range 1 nM–10 μM was well tolerated by the Hypo-E22 cell line. Moreover, kisspeptin-10 (100 nM–10 μM) concentration independently increased the gene expression of NPY while BDNF was inhibited only at the concentration of 10 μM. Finally, kisspeptin-10 decreased 5-HT and DA, leaving unaffected NE levels. The inhibitory effect on DA and 5-HT is consistent with the increased peptide-induced DOPAC/DA and 5-HIIA/5-HT ratios. In conclusion, our current findings suggesting the increased NPY together with decreased BDNF and 5-HT activity following kisspeptin-10 would be consistent with a possible orexigenic effect induced by the peptide.

scholarly journals Effect of GABA-T on Reproductive Function in Female Rats

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 567
Author(s):  
Wenyu Si ◽  
Hailing Li ◽  
Tiezhu Kang ◽  
Jing Ye ◽  
Zhiqiu Yao ◽  
...  
Keyword(s):  
Mrna Level ◽  
Reproductive Function ◽  
Female Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Lactation Performance ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Expression Of Genes

This study explored the role of γ-aminobutyric acid transaminase (GABA-T) in the puberty and reproductive performance of female rats. Immunofluorescence technique, quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution of GABA-T and the expression of genes and hormones in female rats, respectively. The results showed that GABA-T was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and periventricular nucleus (PeN) of the hypothalamus, and in the adenohypophysis, ovarian granulosa cells and oocytes. Abat mRNA level at 28 d was lowest in the hypothalamus and the pituitary; at puberty, it was lowest in the ovary. Abat mRNA level was highest in adults in the hypothalamus; at infancy and puberty, it was highest in the pituitary; and at 21 d it was highest in the ovary. After vigabatrin (GABA-T irreversible inhibitor) was added to hypothalamus cells, the levels of Abat mRNA and Rfrp-3 mRNA were significantly reduced, but Gnrh mRNA increased at the dose of 25 and 50 μg/mL; Kiss1 mRNA was significantly increased but Gabbr1 mRNA was reduced at the 50 μg/mL dose. In prepubertal rats injected with vigabatrin, puberty onset was delayed. Abat mRNA, Kiss1 mRNA and Gnrh mRNA levels were significantly reduced, but Rfrp-3 mRNA level increased in the hypothalamus. Vigabatrin reduced the concentrations of GABA-T, luteinizing hormone (LH) and progesterone (P4), and the ovarian index. Lactation performance was reduced in adult rats with vigabatrin treatment. Four hours after vigabatrin injection, the concentrations of GABA-T and LH were significantly reduced in adult and 25 d rats, but follicle-stimulating hormone (FSH) increased in 25 d rats. In conclusion, GABA-T affects the reproductive function of female rats by regulating the levels of Gnrh, Kiss1 and Rfrp-3 in the hypothalamus as well as the concentrations of LH and P4.

035. THE ROLE OF THE SERTOLI CELL IN REGULATING SPERMATOGENESIS, IMMUNE RESPONSES AND INFLAMMATORY DISEASE: MULTIPLE FUNCTIONS, COMMON MECHANISMS?

2009 ◽  
Vol 21 (9) ◽  
pp. 8
Author(s):  
M. P. Hedger ◽  
J. A. Muir ◽  
W. R. Winnall
Keyword(s):  
Sertoli Cell ◽  
Inflammatory Cytokines ◽  
Cell Function ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Tight Junction Formation ◽  
Interleukin 1Α ◽  
Factor Α ◽  
Necrosis Factor

There is increasing evidence that the Sertoli cell, in addition to modulating responses to direct antigenic challenges (eg. intratesticular allografts), is central to the response of the testis to inflammation and infection. Systemic inflammation exerts an inhibitory effect on spermatogenesis, which has been attributed to the effects of fever, vascular disturbances, or loss of androgenic support. However, recent studies point to more direct effects of inflammation on spermatogenesis. The discovery that Sertoli cells express Toll-like receptors (TLR), and react to TLR ligands by producing inflammatory cytokines and other mediators, provides a mechanism to account for this direct inhibition. Moreover, the pattern of cytokines produced by the Sertoli cell during inflammation is highly characteristic. For example, when stimulated with TLR ligands the Sertoli cell produces the pro-inflammatory cytokines, interleukin-1α (IL1α) and IL6, and the regulatory cytokine, activin A, but does not produce IL1β and tumour necrosis factor-α, which are major pro-inflammatory products of activated macrophages. The disruptive effects of inflammation on spermatogenesis may be attributed to the elevated production of these cytokines, all of which have stimulatory or inhibitory effects on germ cell mitosis, meiosis and apoptosis and Sertoli cell tight junction formation, In addition, activation of TLR/IL1 mediated inflammatory pathways in the Sertoli cell inhibits its ability to respond to its principal trophic hormone, follicle-stimulating hormone. Studies on the regulation of these interactions will further establish the role of the Sertoli cell in inflammation and infection. However, such studies also have important implications for normal Sertoli cell function, as TLRs can respond to endogenous ligands as well. Consequently, the Sertoli cell may be viewed as a sentinel cell, supporting and protecting spermatogenesis when conditions are optimal, but rapidly shutting down spermatogenesis in the presence of infection or illness. Intriguingly, these apparently disparate roles appear to involve common inflammation-related mechanisms.

scholarly journals Definition of the hypothalamic GnRH pulse generator in mice

2017 ◽  
Vol 114 (47) ◽  
pp. E10216-E10223 ◽  
Author(s):  
Jenny Clarkson ◽  
Su Young Han ◽  
Richard Piet ◽  
Timothy McLennan ◽  
Grace M. Kane ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Generation ◽  
Neuron Population ◽  
Lh Pulsatility ◽  
Freely Behaving ◽  
Definition Of ◽  
Lh Secretion

The pulsatile release of luteinizing hormone (LH) is critical for mammalian fertility. However, despite several decades of investigation, the identity of the neuronal network generating pulsatile reproductive hormone secretion remains unproven. We use here a variety of optogenetic approaches in freely behaving mice to evaluate the role of the arcuate nucleus kisspeptin (ARNKISS) neurons in LH pulse generation. Using GCaMP6 fiber photometry, we find that the ARNKISS neuron population exhibits brief (∼1 min) synchronized episodes of calcium activity occurring as frequently as every 9 min in gonadectomized mice. These ARNKISS population events were found to be near-perfectly correlated with pulsatile LH secretion. The selective optogenetic activation of ARNKISS neurons for 1 min generated pulses of LH in freely behaving mice, whereas inhibition with archaerhodopsin for 30 min suppressed LH pulsatility. Experiments aimed at resetting the activity of the ARNKISS neuron population with halorhodopsin were found to reset ongoing LH pulsatility. These observations indicate the ARNKISS neurons as the long-elusive hypothalamic pulse generator driving fertility.

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