Cited by 260Hypothalamic control of reproductive hormonesReproductive Biology and FertilitySperm and Testicular Function

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GnRH signaling, the gonadotrope and endocrine control of fertility

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Bliss, Stuart P., Navratil, Amy M., Xie, Jianjun, Roberson, Mark S.·2010·Frontiers in Neuroendocrinology

DOI 10.1016/j.yfrne.2010.04.002PMC PMC2923852

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Abstract

Mammalian reproductive cycles are controlled by an intricate interplay between the hypothalamus, pituitary and gonads. Central to the function of this axis is the ability of the pituitary gonadotrope to appropriately respond to stimulation by gonadotropin-releasing hormone (GnRH). This review focuses on the role of cell signaling and in particular, mitogen-activated protein kinase (MAPK) activities regulated by GnRH that are necessary for normal fertility. Recently, new mouse models making use of conditional gene deletion have shed new light on the relationships between GnRH signaling and fertility in both male and female mice. Within the reproductive axis, GnRH signaling is initiated through discrete membrane compartments in which the receptor resides leading to the activation of the extracellular signal-regulated kinases (ERKs 1/2). As defined by gonadotrope-derived cellular models, the ERKs appear to play a central role in the regulation of a cohort of immediate early genes that regulate the expression of late genes that, in part, define the differentiated character of the gonadotrope. Recent data would suggest that in vivo, conditional, pituitary-specific disruption of ERK signaling by GnRH leads to a gender-specific perturbation of fertility. Double ERK knockout in the anterior pituitary leads to female infertility due to LH biosynthesis deficiency and a failure in ovulation. In contrast, male mice are modestly LH deficient; however, this does not have an appreciable impact on fertility.

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1 retracted

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Authors: Bliss, S. P., Navratil, A. M., Xie, J., & Roberson, M. S.
Affiliations: Cornell University (US)
Corresponding author: Roberson, Mark S.
ORCID: Roberson, Mark S.
Venue: Frontiers in Neuroendocrinology
Publisher: Elsevier BV
Published: 2010-07
Volume: 31
Issue: 3
Pages: 322-340
ISSN: 0091-3022 (ISSN-L)
DOI: 10.1016/j.yfrne.2010.04.002
PMC: PMC2923852
OpenAlex: W1981942998
Cited by: 259
References: 321
Citations by year: 2026: 15 · 2025: 16 · 2024: 11 · 2023: 21 · 2022: 17 · 2021: 26 · 2020: 18 · 2019: 13 · 2018: 19 · 2017: 20 · 2016: 11 · 2015: 8 · 2014: 16 · 2013: 18 · 2012: 15
FWCI: 2.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Frontiers in Neuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD34722, R01HD034722)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords: gonadotropin-releasing hormone, GnRH signaling, fertility, mitogen-activated protein kinase, ERK1/2, hypothalamic-pituitary-gonadal axis, ovulation, female infertility, male fertility, conditional gene deletion, immediate early genes
MeSH terms: Animals, Endocrine System, Female, Fertility, Gonads, Humans, Hypothalamo-Hypophyseal System, Gonadotropin-Releasing Hormone, Male, Models, Biological, Signal Transduction, Mice, Gonadotrophs

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GnRH signaling, the gonadotrope and endocrine control of fertility

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