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Estrogen Negative Feedback on Gonadotropin Secretion: Evidence for a Direct Pituitary Effect in Women
Open accessAbstract
Context: Studies in humans and animals indicate that estrogen negative feedback occurs at the level of the hypothalamus, but it is unclear whether estrogen also exerts an inhibitory effect directly at the pituitary. Objectives: The aim of the study was to determine whether estrogen has a direct negative feedback effect at the pituitary and whether this varies with aging. Design and Setting: A GnRH antagonist and graded doses of GnRH were used to isolate pituitary responsiveness before and after estrogen administration in Clinical Research Center studies at an academic medical center. Subjects: Subjects were healthy postmenopausal women aged 48–56 yr (n = 8) or 70–75 yr (n= 8). Interventions: A suppressive dose of the NAL-GLU GnRH antagonist was administered, followed by graded doses of GnRH before and after 1 month of estrogen administration. Results: LH and FSH responses to GnRH decreased after estrogen administration (P = 0.01 and P = 0.0001, respectively). The ratio of FSH to LH amplitudes decreased in response to estrogen (P = 0.04) indicating a greater sensitivity of FSH than LH to inhibition by estrogen. The inhibitory effect of estrogen on FSH was attenuated with aging (P = 0.02), but was maintained for LH (P = 0.4). Conclusions: Studies that control for endogenous GnRH and estradiol demonstrate a direct pituitary site of estrogen negative feedback on LH and FSH responsiveness to GnRH in women. The effect of estrogen on FSH responsiveness is greater than on LH and is attenuated with aging. These studies indicate that estrogen negative feedback occurs directly at the pituitary and contributes to the differential regulation of FSH and LH secretion.
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“The release of FSH from the pituitary, Rel FSH t ð Þ, is stimulated by the active GnRH receptor complex, GR a t ð Þ and inhibited by the amount of E2 (Shaw et al., 2010).”
From Hormonal regulation of ovarian follicle growth in humans: Model-based exploration of cycle variability and parameter sensitivities (2022) · cites this paper as Shaw et al., 2010
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Metadata
- Authors
- Shaw, N. D., Histed, S. N., Srouji, S. S., Yang, J., Lee, H., & Hall, J. E.
- Affiliations
- Boston Children's Hospital (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Hall, J. E.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-04-01
- Volume
- 95
- Issue
- 4
- Pages
- 1955-1961
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2853991
- OpenAlex
- W2137215560
- Cited by
- 149
- References
- 52
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 14 · 2023: 9 · 2022: 11 · 2021: 7 · 2020: 15 · 2019: 13 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 5 · 2012: 6
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- National Institutes of Health
- National Institute on Aging (R01 AG 13241, R01AG013241)
- National Center for Research Resources (M01RR001066, M01-RR01066)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007396, F32HD062315)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Keywords
- estrogen negative feedback, pituitary gland, gonadotropin secretion, follicle-stimulating hormone, luteinizing hormone, gonadotropin-releasing hormone, postmenopausal women, aging, hypothalamic-pituitary-gonadal axis, estradiol
- MeSH terms
- Administration, Cutaneous, Adult, Aged, Aging, Dose-Response Relationship, Drug, Estradiol, Estrogens, Female, Follicle Stimulating Hormone, Gonadotropins, Humans, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Middle Aged, Pituitary Gland, Estrogen Replacement Therapy, Feedback, Physiological
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