Kisspeptin-54 Stimulates the Hypothalamic-Pituitary Gonadal Axis in Human Males

Dhillo, Waljit S.; Chaudhri, Owais B.; Patterson, Michael; Thompson, Emily L.; Murphy, Kevin G.; Badman, Michael K.; McGowan, Barbara; Amber, Vian; Patel, Suhani; Ghatei, Mohammad A.; Bloom, Stephen R.

doi:10.1210/jc.2005-1468

Cited by 569 publications

(309 citation statements)

References 31 publications

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“…These animals have low circulating levels of gonadotropins, reflecting diminished GnRH secretion, which may be attributable to a lack of trophic activation from kisspeptin. Indeed, kisspeptin stimulates GnRH secretion by a direct action on GnRH neurons, virtually all of which express GPR54 (Gottsch et al, 2004;Dhillo et al, 2005;Irwig et al, 2005;Messager et al, 2005;Navarro et al, 2005;Ramaswamy et al, 2007). E exerts dramatic, but opposite, effects on Kiss1 mRNA expression in the AVPV and Arc (in the Arc, E inhibits the expression of Kiss1, whereas in the AVPV, E induces the expression of Kiss1) .…”

Section: Introductionmentioning

confidence: 99%

The Role of Kisspeptin–GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone

Dungan¹,

Gottsch²,

Zeng³

et al. 2007

J. Neurosci.

196

144

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The Kiss1 gene codes for kisspeptin, which binds to GPR54, a G-protein-coupled receptor. Kisspeptin and GPR54 are expressed in discrete regions of the forebrain, and they have been implicated in the neuroendocrine regulation of reproduction. Kiss1-expressing neurons are thought to regulate the secretion of gonadotropin-releasing hormone (GnRH) and thus coordinate the estrous cycle in rodents; however, the precise role of kisspeptin-GPR54 signaling in the regulation of gonadotropin secretion is unknown. In this study, we used female mice with deletions in the GPR54 gene [GPR54 knock-outs (KOs)] to test the hypothesis that kisspeptin-GPR54 signaling provides the drive necessary for tonic GnRH/luteinizing hormone (LH) release. We predicted that tonic GnRH/LH secretion would be disrupted in GPR54 KOs and that such animals would be incapable of showing a compensatory rise in LH secretion after ovariectomy. As predicted, we found that GPR54 KO mice do not exhibit a postovariectomy rise in LH, suggesting that tonic GnRH secretion is disrupted in the absence of kisspeptin-GPR54 signaling. We also postulated that kisspeptin-GPR54 signaling is critical for the generation of the estradiol (E)-induced GnRH/LH surge and thus E should be incapable of inducing an LH surge in the absence of GPR54. However, we found that E induced Fos expression in GnRH neurons and produced a GnRH-dependent LH surge in GPR54 KOs. Thus, in mice, kisspeptin-GPR54 signaling is required for the tonic stimulation of GnRH/LH secretion but is not required for generating the E-induced GnRH/LH surge.

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Section: Introductionmentioning

confidence: 99%

The Role of Kisspeptin–GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone

Dungan¹,

Gottsch²,

Zeng³

et al. 2007

J. Neurosci.

196

144

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“…infusion of kisspeptin results in a significant increase in plasma LH, FSH and testosterone (Dhillo et al 2005). S.c. injection of kisspeptin to healthy pre-menopausal female subjects elicits a marked rise in LH, which is most pronounced in the preovulatory phase of the menstrual cycle (Dhillo et al 2007).…”

Section: Kisspeptin Provides a Link Between Nutritional Status And Fementioning

confidence: 96%

“…and peripheral administration of kisspeptin result in a marked rise in plasma LH and to a lesser extent FSH in several mammalian species including rats, mice, sheep, monkeys and humans. This effect is abolished in GPR54 K/K mice , Thompson et al 2004, Dhillo et al 2005, Messager et al 2005. The effect of kisspeptin on gonadotrophin release is likely to be due to kisspeptin stimulation of GnRH release into the portal circulation, which in turn stimulates the release of LH and FSH from the gonadotrophs of the anterior pituitary gland.…”

Section: The Kisspeptin Receptormentioning

confidence: 98%

“…injection without any observed adverse effects (Dhillo et al 2005(Dhillo et al , 2007. In particular, kisspeptin has not been shown to cause changes in heart rate or blood pressure, which is important in view of the vasoconstrictor properties of kisspeptin that have been demonstrated in vitro (Mead et al 2007.…”

Section: Kisspeptin Provides a Link Between Nutritional Status And Fementioning

confidence: 99%

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Kisspeptin and fertility

Hameed¹,

Jayasena²,

Dhillo³

2010

Journal of Endocrinology

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The kisspeptins are a familyof peptide hormones, which in recent years have been shown to play a critical role in the regulation of the hypothalamic-pituitary-gonadal axis, thus in turn influencing fertility and reproduction. This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and the implications of these findings with respect to fertility. In addition, the potential therapeutic use of kisspeptin in the treatment of reproductive disorders will be examined.

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“…Как уже обсуж-далось, кисспептин и KISS1R расцениваются как важнейшие регуляторы наступления полового созревания и секреции гонадотропинов [113]. Установлено, что комплекс кисспептин/GPR54 стимулирует активацию ГГя-оси и регулирует энергетический обмен [114][115][116]. Недавние ис-следования показали, что содержание кисспеп-тина достоверно выше у девочек с центральной формой преждевременного полового созревания по сравнению с уровнем данного белка у девочек в препубертатном периоде [117,118].…”

Section: содержание кисспептина у девочек с преждевременным телархеunclassified

Role of Kisspeptine in Regulation of Reproductive Function

et al. 2016

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Research objective: to identify a role of kisspeptine in the regulation of reproduction function.Materials: literature data by foreign authors for the period from 1985 till 2016.Methods: systematic analysis and compilation of information in the literature.Results. The article provides a review of literature data on research of kisspeptine gene and its receptor; it includes description of their role in regulation of reproduction function and mutation in the genes responsible for realization of kisspeptine and neurokinin signaling pathways. Features of kisspeptine secretion in patients with hypogonadotropic hypogonadism, premature sexual development, hyperprolactinemic deficiency of ovaries, polycystic ovarian syndrome, genital endometriosis and opportunity of kisspeptine use in clinical practice as an ovulation trigger are described.Conclusion. It is necessary to carry out further studies for clarification of kisspeptine role in patients with various diseases and the opportunity of its use as a therapeutic target.

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Kisspeptin-54 Stimulates the Hypothalamic-Pituitary Gonadal Axis in Human Males

Abstract: Elevation of plasma concentrations of kisspeptin in human males significantly increases circulating LH, FSH, and testosterone levels. Kisspeptin infusion provides a novel mechanism for hypothalamic-pituitary-gonadal axis manipulation in disorders of the reproductive system.

Cited by 569 publications

References 31 publications

The Role of Kisspeptin–GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone

The Role of Kisspeptin–GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone

Kisspeptin and fertility

Role of Kisspeptine in Regulation of Reproductive Function

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