GnRH Pulsatility, the Pituitary Response and Reproductive Dysfunction
Open accessAbstract
GnRH plays an essential role in neuroendocrine control of reproductive function. In mammals, the pattern of gonadotropin secretion includes both pulse and surge phases, which are regulated independently. The pulsatile release of GnRH and LH plays an important role in the development of sexual function and in the normal regulation of the menstrual cycle. The importance of GnRH pulsatility was established in a series of classic studies. Fertility is impaired when GnRH pulsatility is inhibited by chronic malnutrition, excessive caloric expenditure, or aging. A number of reproductive disorders in women with including hypogonadotropic hypogonadism, hypothlamic amenorrhea, hyperprolactinemia and polycystic ovary syndrome (PCOS) are also associated with disruption of the normal pulsatile GnRH secretion. Despite these findings, the molecular mechanisms of this pulsatile GnRH regulation are not well understood. Here, we review recent studies about GnRH pulsatility, signaling and transcriptional response, and its implications for disease.
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In women with hypogonadotrophic hypogonadism, regular ovulatory cycles can be reinstated by timed pulsatile infusion of GnRH but not by similar levels of GnRH delivered constantly.
“In women with hypogonadotrophic hypogonadism, regular ovulatory cycles can be reinstated by the timed pulsatile infusion of GnRH but not by similar levels of GnRH delivered in a constant fashion (Tsutsumi & Webster, 2009).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Tsutsumi & Webster, 2009
The Introduction says disrupted GnRH pulsatility is associated with hypogonadotropic hypogonadism in women. It also reports that intermittent, but not constant, GnRH administration restored sustained gonadotropin secretion in rhesus monkeys. It does not report reinstated regular ovulatory cycles in women or compare similar GnRH doses delivered by the two methods. (LLM, conf=0.83)
Experimental — accuracy not yet measuredGnRH pulses are required for reproductive functions in both sexes.
“GnRH pulses are required for reproductive functions in both sexes, and the importance of these pulses in driving reproduction has been described in primates and humans (Tsutsumi & Webster, 2009).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Tsutsumi & Webster, 2009
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- Authors
- TSUTSUMI, R., & WEBSTER, N. J. G.
- Affiliations
- University of California System (US)
- Corresponding author
- WEBSTER, Nicholas J.G.
- Venue
- Endocrine Journal
- Publisher
- Japan Endocrine Society
- Published
- 2009
- Volume
- 56
- Issue
- 6
- Pages
- 729-737
- ISSN
- 0918-8959 (ISSN-L)
- 1348-4540
- PMC
- PMC4307809
- OpenAlex
- W2068905180
- Cited by
- 317
- References
- 51
- Citations by year
- 2026: 28 · 2025: 24 · 2024: 39 · 2023: 26 · 2022: 25 · 2021: 28 · 2020: 34 · 2019: 11 · 2018: 16 · 2017: 13 · 2016: 12 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 13
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Journal (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063491)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD012303, U54HD012303, R01HD047400)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- GnRH pulsatility, gonadotropin secretion, luteinizing hormone surge, gonadotrophs, reproductive disorders, hypogonadotropic hypogonadism, hypothalamic amenorrhea, hyperprolactinemia, polycystic ovary syndrome, menstrual cycle regulation, GnRH signaling, fertility
- MeSH terms
- Animals, Female, Humans, Infertility, Gonadotropin-Releasing Hormone, Male, Pituitary Gland, Reproduction
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