Role of Kisspeptin on Hypothalamic-Pituitary-Gonadal Pathology and Its Effect on Reproduction

Padda, Jaskamal; Khalid, Khizer; Moosa, Amir; Syam, Mohammad; Kakani, Varsha; Imdad, Urooj; Ismail, Dina; Cooper, Ayden Charlene; Jean-Charles, Gutteridge

doi:10.7759/cureus.17600

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…KPs are expressed in high levels in the brain, particularly in the hypothalamic region [ 102 ]. In addition to the hypothalamus, KPRs are expressed in the pons, midbrain, thalamus, hippocampus, amygdala, cortex, frontal cortex, and striatum [ 103 ]. Rodent KP neurons are located in two major brain regions: ARC and AVPV nuclei [ 104 , 105 , 106 ] ( Figure 6 ).…”

Section: Sexual Dimorphism In Hypothalamic Kisspeptin Expressionmentioning

confidence: 99%

Sexual Dimorphism in Kisspeptin Signaling

Lee

Dilower

Marsh

et al. 2022

Cells

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Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and females. Hypothalamic KPs and KPR display a high degree of sexual dimorphism in expression and function. KPs act on KPR in gonadotropin releasing hormone (GnRH) neurons and induce distinct patterns of GnRH secretion in males and females. GnRH acts on the anterior pituitary to secrete gonadotropins, which are required for steroidogenesis and gametogenesis in testes and ovaries. Gonadal steroid hormones in turn regulate the KP neurons. Gonadal hormones inhibit the KP neurons within the arcuate nucleus and generate pulsatile GnRH mediated gonadotropin (GPN) secretion in both sexes. However, the numbers of KP neurons in the anteroventral periventricular nucleus and preoptic area are greater in females, which release a large amount of KPs in response to a high estrogen level and induce the preovulatory GPN surge. In addition to the hypothalamus, KPs and KPR are also expressed in various extrahypothalamic tissues including the liver, pancreas, fat, and gonads. There is a remarkable difference in circulating KP levels between males and females. An increased level of KPs in females can be linked to increased numbers of KP neurons in female hypothalamus and more KP production in the ovaries and adipose tissues. Although the sexually dimorphic features are well characterized for hypothalamic KPs, very little is known about the extrahypothalamic KPs. This review article summarizes current knowledge regarding the sexual dimorphism in hypothalamic as well as extrahypothalamic KP and KPR system in primates and rodents.

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Section: Sexual Dimorphism In Hypothalamic Kisspeptin Expressionmentioning

confidence: 99%

Sexual Dimorphism in Kisspeptin Signaling

Lee

Dilower

Marsh

et al. 2022

Cells

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“…Kisspeptin, produced by kisspeptin neurons located in the hypothalamus, is a neuropeptide hormone responsible for stimulating the GnRH secretion, crucial for the normal function of the HPT axis [ 48 , 49 ]. More recently, the role of kisspeptin on the pathology of the HPT and its impact on human reproduction was highlighted [ 50 ]. Indeed, this signaling system is considered an essential regulatory part of the HPT axis, since its pulsatility, together with GnRH pulses, are essential for sexual maturation [ 51 , 52 ].…”

Section: Carbamates and Kisspeptinmentioning

confidence: 99%

Carbamate Pesticides: Shedding Light on Their Impact on the Male Reproductive System

Moreira

Silva

Carrageta

et al. 2022

IJMS

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Carbamates are widely used and known around the world as pesticides in spite of also having medical applications. This class of chemicals is classified as acetylcholinesterase inhibitors, blocking acetylcholine hydrolyzation in a reversible manner. Their lack of species selectivity and their reported high toxicity can induce, upon exposure, adverse outcomes in male fertility that may lead to infertility. In addition, they are also considered endocrine-disrupting chemicals and can interfere with the hypothalamic–pituitary–testicular axis, essential for the normal function of the male reproductive system, thus being able to provoke male reproductive dysfunctions. Although the molecular mechanisms are not fully understood, various signaling pathways, such as those mediated by acetylcholine or kisspeptin, are affected by exposure to carbamates, thus compromising steroidogenesis and spermatogenesis. Over the last decades, several studies, both in vitro and in vivo, have reported a myriad of negative effects of carbamates on the male reproductive system. In this review, an up-to-date overview of the impact of carbamates on the male reproductive system is discussed, with an emphasis on the role of these compounds on acetylcholine regulation and the male endocrine system.

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“…Increased LH pulse frequencies are commonly reported in women with PCOS [ 10 ]. This pattern indicates the increased pulse frequency stimulation by gonadotropin-releasing hormone (GnRH) and increased activity of GnRH neurons upstream in the hypothalamus [ 11 ]. Compared with healthy women, patients with PCOS require higher concentrations of exogenous estradiol (E 2 ) and progesterone to slow their high-frequency pulsatile LH release [ 12 , 13 ].…”

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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Role of Kisspeptin on Hypothalamic-Pituitary-Gonadal Pathology and Its Effect on Reproduction

Cited by 13 publications

References 31 publications

Sexual Dimorphism in Kisspeptin Signaling

Sexual Dimorphism in Kisspeptin Signaling

Carbamate Pesticides: Shedding Light on Their Impact on the Male Reproductive System

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

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