Cited by 149Hypothalamic control of reproductive hormonesEstrogen and related hormone effectsReproductive Biology and Fertility

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Estrogen Negative Feedback on Gonadotropin Secretion: Evidence for a Direct Pituitary Effect in Women

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Shaw, N. D., Histed, S. N., Srouji, S. S., Yang, J., Lee, H., Hall, J. E.·2010·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2009-2108PMC PMC2853991

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Abstract

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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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.
ORCID: Shaw, N. D.
Lee, H.
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
DOI: 10.1210/jc.2009-2108
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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Estrogen Negative Feedback on Gonadotropin Secretion: Evidence for a Direct Pituitary Effect in Women

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