Leptin and the Hypothalamic-Pituitary Regulation of the Gonadotropin-Gonadal Axis

Chan, Jean L.; Mantzoros, Christos S.

doi:10.1023/a:1012947113197

Cited by 124Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityReproductive Biology and Fertility

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Leptin and the Hypothalamic-Pituitary Regulation of the Gonadotropin-Gonadal Axis

Chan, Jean L., Mantzoros, Christos S.·2001·Pituitary

DOI 10.1023/a:1012947113197

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Abstract

Leptin is an adipocyte-derived protein hormone which not only conveys a signal of the amount of energy stores to the central nervous system but also plays an important role in regulating neuroendocrine function. The importance of leptin in the reproductive system has been suggested by the reproductive dysfunction associated with leptin deficiency and resistance in both animal models and humans as well as the ability of leptin to accelerate the onset of reproductive function in normal mice. Transgenic mice overexpressing leptin also have accelerated puberty, and leptin administration reverses the fasting-induced suppression of sexual maturation in rodents, indicating that leptin may serve as the critical link between sufficient energy stores and proper functioning of the reproductive system. Normal women have a pulsatile release pattern of leptin that is significantly associated with the variations in luteinizing hormone (LH) and estradiol levels. In various animal models, leptin administration restores the LH pulsatility pattern which is suppressed during fasting, indicating a hypothalamic site of action since LH pulsatility is under the control of gonadotropin-releasing hormone (GnRH). In humans, leptin has been administered to a 9-year-old leptin-deficient girl, resulting in a gonadotropin secretory pattern consistent with early puberty. While in vitro experiments with hypothalamic explants and a GnRH-secreting neuronal cell line have shown that leptin can directly stimulate GnRH secretion, the lack of leptin receptors on GnRH neurons suggests that leptin may act through other hypothalamic neuropeptides. Several neuropeptides which act as downstream effectors of leptin have been investigated, and recent studies indicate that cocaine and amphetamine-regulated transcript may be such a mediator of leptin's effect on GnRH. Leptin receptors have also been identified in human pituitaries, and leptin may influence LH release from the pituitary. However, the current evidence is conflicting, and further studies are needed in order to clarify leptin's role at the level of the pituitary. Thus, accumulating evidence suggests that leptin can regulate gonadotropin levels, and its secretion may, in turn, be influenced by GnRH or gonadal steroids but appears to be independent of LH control.

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The effect of low leptin on LH pulsatility is most likely secondary to effects on the hypothalamus to influence pulsatile GnRH release.
“This effect of low leptin on LH pulsatility is most likely secondary to effects on the hypothalamus to influence pulsatile GnRH release, on the basis of in vitro and animal data (27)”
From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [27]

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Authors: Chan, J. L., & Mantzoros, C. S.
Affiliations: Beth Israel Deaconess Medical Center (US)
Corresponding author: Chan, Jean L.
ORCID: Mantzoros, Christos S.
Venue: Pituitary
Publisher: Springer Science and Business Media LLC
Published: 2001-01
Volume: 4
Issue: 1-2
Pages: 87-92
ISSN: 1386-341X (ISSN-L)
1573-7403
DOI: 10.1023/a:1012947113197
OpenAlex: W9174261
Cited by: 124
References: 60
Citations by year: 2026: 6 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 1 · 2021: 7 · 2020: 4 · 2019: 30 · 2018: 3 · 2017: 1 · 2016: 7 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 3
FWCI: 2.86
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Pituitary (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Keywords: leptin, hypothalamic-pituitary-gonadal axis, gonadotropin-releasing hormone, luteinizing hormone, GnRH neurons, leptin receptor, neuropeptides, CART, puberty, energy homeostasis, leptin resistance, estradiol, gonadotropin secretion
MeSH terms: Animals, Gonadotropins, Gonads, Humans, Hypothalamo-Hypophyseal System, Reproduction, Leptin

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Leptin and the Hypothalamic-Pituitary Regulation of the Gonadotropin-Gonadal Axis

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