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GnRH signaling, the gonadotrope and endocrine control of fertility
Open accessAbstract
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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“The resultant phenotype was female-specific anovulatory infertility due to a loss of luteinizing hormone (LH) β subunit expression resulting in an inability to mount a preovulatory surge of LH.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [4]
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“In past studies, we reported a pituitary-specific conditional ERK double knockout (ERKdko) using the ERK1 null and ERK2 floxed alleles combined with a Cre recombinase driver regulated by the gene promoter for the α subunit to the glycoprotein hormones (αGSU)3,4 and the gonadotrope-specific Cre driver (GRIC)12,13.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [4]
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Metadata
- 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)
- 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
- 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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