Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System

Prashar, Vikash; Arora, Tania K.; Singh, Randeep; Sharma, Anil Kumar; Parkash, Jyoti

doi:10.1007/s43032-022-01027-5

Cited by 8 publications

(3 citation statements)

References 207 publications

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“…There is increasing evidence suggesting that kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which are located in the arcuate nucleus (ARC), are associated with hyperactive GnRH/LH pulses in PCOS [18][19][20][21]. KNDy neurons secrete kisspeptin that regulates GnRH neurons via the kisspeptin-Kiss1r (Kiss1r) signaling pathway, which in turn regulates the hypothalamic-pituitarygonadal (HPG) axis function [22,23].…”

Section: Introductionmentioning

confidence: 99%

Effects of electroacupuncture on the kisspeptin-gonadotropin-releasing hormone (GnRH) /luteinizing hormone (LH) neural circuit abnormalities and androgen receptor expression of kisspeptin/neurokinin B/dynorphin neurons in PCOS rats

Zhao

et al. 2023

J Ovarian Res

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Background Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Electroacupuncture (EA) can effectively improve hyperandrogenism and increase ovulation frequency in patients with PCOS. Pieces of suggest that androgen activity in the brain is associated with impaired steroid negative feedback in such patients. Studies have shown that EA regulated androgen receptor (AR) expression and local factor levels (such as anti-Müllerian hormone and inhibin B) in the ovary of PCOS rats. However, few studies have explored the effect of EA on androgen activity in the brain. Objective This study investigated the effect of EA on the kisspeptin-gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) neural circuit and sex hormone receptor expression in the hypothalamus of PCOS rats. Methods PCOS signs were induced by letrozole administration, and the induced rats were treated with low-frequency EA at Guan Yuan acupoint (CV4). The effect of EA on PCOS-like signs was evaluated by observing changes in the body weight, ovarian quality, ovarian morphology, and serum sex hormone levels in rats. To explore the mechanism of the effect of EA on PCOS-like signs, the neuropeptide content of the kisspeptin-GnRH/LH neural circuit was assessed using enzyme-linked immunosorbent assay(ELISA); AR and estrogen receptor α (ERα) coexpression on kisspeptin/neurokinin B/dynorphin (KNDy) neurons was determined via triple-label immunofluorescence; and protein and mRNA expression of Kiss1, Ar, Esr1, and kisspeptin receptor (Kiss1r) was evaluated via western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results The results revealed that the estrous cycle of rats in the EA treatment group recovered, and their body and ovary weight reduced; ovarian morphology improved; serum testosterone and LH levels significantly decreased; and kisspeptin, GnRH, and dynorphin levels in hypothalamic arcuate nucleus significantly decreased. Compared with controls, the number of AR/Kiss1-positive cells increased, number of ERα/Kiss1-positive cells decreased, and protein and mRNA expression of Kiss1, Ar, and Kiss1r significantly increased in PCOS rats. However, EA treatment reversed these changes and reduced the expression of Kiss1, Ar, and Kiss1r significantly. Conclusion Improvement in the reproductive hallmarks of PCOS rats via EA may be achieved by regulating the kisspeptin-GnRH/LH circuit via androgen activity attenuation. Thus, the results provide an experimental basis for acupuncture as an adjuvant medical therapy on PCOS.

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Section: Introductionmentioning

confidence: 99%

Effects of electroacupuncture on the kisspeptin-gonadotropin-releasing hormone (GnRH) /luteinizing hormone (LH) neural circuit abnormalities and androgen receptor expression of kisspeptin/neurokinin B/dynorphin neurons in PCOS rats

Zhao

et al. 2023

J Ovarian Res

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“…It acts as a potent stimulator of the release of gonadotropin-releasing hormone (GnRH) in the brain [27]. GnRH serves as the key mediator, conveying these cues throughout the HPG axis [28]. Over the past twenty years, significant research has been dedicated to studying the Kisspeptin (KISS1) neurotransmitter, and a growing body of evidence supports their involvement in regulating the secretion of GnRH and gonadotropin hormones throughout the ovulatory cycle [29].…”

Section: Introductionmentioning

confidence: 99%

Impact of Perinatal Co-exposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs

Lahimer,

Djekkoun,

Tricotteaux-Zarqaoui

et al. 2023

Preprint

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Emerging evidence has indicated the involvement of extra-hypothalamic kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) have an impact on the expression of kisspeptin and GnRHR in reproductive organ of offspring’s rats. 16 Pregnant rats are divided into 4 groups, control group (n=4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5,25 kcal/g HFD), co-exposed group (4 rats exposed to CPF and HDF). At postnatal development PND60, males and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed and histological, immunohistological analysis and in silico quantification (software Tissuefax, HistoQuest) was assessed to investigate the impact of different treatment on kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring’s body weight in CPF group from PND30 andPND60 (p&lt;0.05 and p&lt;0.01, respectively). Histological analysis shows a significant increase in atretic follicle and abnormal testis structure with germ cell desquamation at CPF exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and kisspeptin in HFD and CPF exposed group, respectively in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.

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“…GnRH release is regulated by a plethora of upstream neuronal signals in the brain ( 5 , 6 ). Kisspeptin is a neuropeptide synthesized in two major populations of hypothalamic neurons.…”

Section: Introductionmentioning

confidence: 99%

Stereology of gonadotropin-releasing hormone and kisspeptin neurons in PACAP gene-deficient female mice

et al. 2022

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The hypothalamic gonadotropin-releasing hormone (GnRH)–kisspeptin neuronal network regulates fertility in all mammals. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide isolated from the hypothalamus that is involved in the regulation of several releasing hormones and trop hormones. It is well-known that PACAP influences fertility at central and peripheral levels. However, the effects of PACAP on GnRH and kisspeptin neurons are not well understood. The present study investigated the integrity of the estrous cycle in PACAP-knockout (KO) mice. The number and immunoreactivity of GnRH (GnRH-ir) neurons in wild-type (WT) and PACAP KO female mice were determined using immunohistochemistry. In addition, the number of kisspeptin neurons was measured by counting kisspeptin mRNA-positive cells in the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus (ARC) using the RNAscope technique. Finally, the mRNA and protein expression of estrogen receptor alpha (ERα) was also examined. Our data showed that the number of complete cycles decreased, and the length of each cycle was longer in PACAP KO mice. Furthermore, the PACAP KO mice experienced longer periods of diestrus and spent significantly less time in estrus. There was no difference in GnRH-ir or number of GnRH neurons. In contrast, the number of kisspeptin neurons was decreased in the ARC, but not in the R3PV, in PACAP KO mice compared to WT littermates. Furthermore, ERα mRNA and protein expression was decreased in the ARC, whereas in the R3PV region, ERα mRNA levels were elevated. Our results demonstrate that embryonic deletion of PACAP significantly changes the structure and presumably the function of the GnRH–kisspeptin neuronal network, influencing fertility.

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Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System

Cited by 8 publications

References 207 publications

Effects of electroacupuncture on the kisspeptin-gonadotropin-releasing hormone (GnRH) /luteinizing hormone (LH) neural circuit abnormalities and androgen receptor expression of kisspeptin/neurokinin B/dynorphin neurons in PCOS rats

Effects of electroacupuncture on the kisspeptin-gonadotropin-releasing hormone (GnRH) /luteinizing hormone (LH) neural circuit abnormalities and androgen receptor expression of kisspeptin/neurokinin B/dynorphin neurons in PCOS rats

Impact of Perinatal Co-exposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs

Stereology of gonadotropin-releasing hormone and kisspeptin neurons in PACAP gene-deficient female mice

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