Pituitary and/or peripheral estrogen-receptor α regulates follicle-stimulating hormone secretion, whereas central estrogenic pathways direct growth hormone and prolactin secretion in postmenopausal women

Mihaela Cosma, Joy Bailey, John M. Miles, Cyril Y. Bowers, Johannes D Veldhuis

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Estradiol (E2) stimulates GH and prolactin secretion and suppresses FSH secretion in postmenopausal women. Whether central nervous system (CNS) or pituitary mechanisms (or both) mediate such actions is not known. Objective: Our objective was to distinguish between hypothalamic and pituitary or peripheral (hepatic) actions of E2. Setting: This study was performed in an academic medical center. Design: This was a double-blind, prospectively randomized, placebo (Pl)-controlled study. Methods: The capability of a selective, noncompetitive, non-CNS permeant estrogen receptor (ER)-α antagonist, fulvestrant (FUL) to antagonize the effects of transdermal E 2 and Pl on GH, prolactin, and FSH secretion was assessed in 43 women (ages 50-80 yr) in a four parallel-cohort study. Each woman received four secretagogue infusions to stimulate GH secretion. IGF-I and its binding proteins were measured secondarily. Results: Administration of Pl/E2 increased GH and prolactin concentrations by 100%, and suppressed FSH concentrations by more than 50% (each P ≤ 0.004 compared with Pl/Pl). Treatment with FUL/E2 compared with Pl/E2 partially relieved estrogen's inhibition of FSH secretion (P = 0.041), without altering E2's stimulation of prolactin secretion. ANOVA further revealed that: 1) estrogen milieu (P = 0.014) and secretagogue type (P < 0.001) each determined GH concentrations; 2) FUL/Pl suppressed IGF-I concentrations (P < 0.001); 3) FUL abrogated estrogen's elevation of IGF binding protein-1 concentrations (P < 0.001); and 4) FUL did not oppose estrogen's suppression of IGF binding protein-3 concentrations (P < 0.001). Summary and Conclusions: Responses to a non-CNS permeant ERα antagonist indicate that E 2 inhibits FSH secretion in part via pituitary/peripheral ERα, drives prolactin output via nonpituitary/nonperipheral-ERα effects, and directs GH secretion and IGF-I-binding proteins by complex mechanisms.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Follicle Stimulating Hormone
Estrogen Receptors
Prolactin
Growth Hormone
Placebos
Estrogens
Neurology
Insulin-Like Growth Factor I
Carrier Proteins
Insulin-Like Growth Factor Binding Protein 1
Nervous System
Insulin-Like Growth Factor Binding Protein 3
Analysis of variance (ANOVA)
Insulin-Like Growth Factor Binding Proteins
Estradiol
fulvestrant
Analysis of Variance
Cohort Studies
Central Nervous System
Liver

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Pituitary and/or peripheral estrogen-receptor α regulates follicle-stimulating hormone secretion, whereas central estrogenic pathways direct growth hormone and prolactin secretion in postmenopausal women. / Cosma, Mihaela; Bailey, Joy; Miles, John M.; Bowers, Cyril Y.; Veldhuis, Johannes D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 3, 03.2008, p. 951-958.

Research output: Contribution to journalArticle

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abstract = "Background: Estradiol (E2) stimulates GH and prolactin secretion and suppresses FSH secretion in postmenopausal women. Whether central nervous system (CNS) or pituitary mechanisms (or both) mediate such actions is not known. Objective: Our objective was to distinguish between hypothalamic and pituitary or peripheral (hepatic) actions of E2. Setting: This study was performed in an academic medical center. Design: This was a double-blind, prospectively randomized, placebo (Pl)-controlled study. Methods: The capability of a selective, noncompetitive, non-CNS permeant estrogen receptor (ER)-α antagonist, fulvestrant (FUL) to antagonize the effects of transdermal E 2 and Pl on GH, prolactin, and FSH secretion was assessed in 43 women (ages 50-80 yr) in a four parallel-cohort study. Each woman received four secretagogue infusions to stimulate GH secretion. IGF-I and its binding proteins were measured secondarily. Results: Administration of Pl/E2 increased GH and prolactin concentrations by 100{\%}, and suppressed FSH concentrations by more than 50{\%} (each P ≤ 0.004 compared with Pl/Pl). Treatment with FUL/E2 compared with Pl/E2 partially relieved estrogen's inhibition of FSH secretion (P = 0.041), without altering E2's stimulation of prolactin secretion. ANOVA further revealed that: 1) estrogen milieu (P = 0.014) and secretagogue type (P < 0.001) each determined GH concentrations; 2) FUL/Pl suppressed IGF-I concentrations (P < 0.001); 3) FUL abrogated estrogen's elevation of IGF binding protein-1 concentrations (P < 0.001); and 4) FUL did not oppose estrogen's suppression of IGF binding protein-3 concentrations (P < 0.001). Summary and Conclusions: Responses to a non-CNS permeant ERα antagonist indicate that E 2 inhibits FSH secretion in part via pituitary/peripheral ERα, drives prolactin output via nonpituitary/nonperipheral-ERα effects, and directs GH secretion and IGF-I-binding proteins by complex mechanisms.",
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T1 - Pituitary and/or peripheral estrogen-receptor α regulates follicle-stimulating hormone secretion, whereas central estrogenic pathways direct growth hormone and prolactin secretion in postmenopausal women

AU - Cosma, Mihaela

AU - Bailey, Joy

AU - Miles, John M.

AU - Bowers, Cyril Y.

AU - Veldhuis, Johannes D

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N2 - Background: Estradiol (E2) stimulates GH and prolactin secretion and suppresses FSH secretion in postmenopausal women. Whether central nervous system (CNS) or pituitary mechanisms (or both) mediate such actions is not known. Objective: Our objective was to distinguish between hypothalamic and pituitary or peripheral (hepatic) actions of E2. Setting: This study was performed in an academic medical center. Design: This was a double-blind, prospectively randomized, placebo (Pl)-controlled study. Methods: The capability of a selective, noncompetitive, non-CNS permeant estrogen receptor (ER)-α antagonist, fulvestrant (FUL) to antagonize the effects of transdermal E 2 and Pl on GH, prolactin, and FSH secretion was assessed in 43 women (ages 50-80 yr) in a four parallel-cohort study. Each woman received four secretagogue infusions to stimulate GH secretion. IGF-I and its binding proteins were measured secondarily. Results: Administration of Pl/E2 increased GH and prolactin concentrations by 100%, and suppressed FSH concentrations by more than 50% (each P ≤ 0.004 compared with Pl/Pl). Treatment with FUL/E2 compared with Pl/E2 partially relieved estrogen's inhibition of FSH secretion (P = 0.041), without altering E2's stimulation of prolactin secretion. ANOVA further revealed that: 1) estrogen milieu (P = 0.014) and secretagogue type (P < 0.001) each determined GH concentrations; 2) FUL/Pl suppressed IGF-I concentrations (P < 0.001); 3) FUL abrogated estrogen's elevation of IGF binding protein-1 concentrations (P < 0.001); and 4) FUL did not oppose estrogen's suppression of IGF binding protein-3 concentrations (P < 0.001). Summary and Conclusions: Responses to a non-CNS permeant ERα antagonist indicate that E 2 inhibits FSH secretion in part via pituitary/peripheral ERα, drives prolactin output via nonpituitary/nonperipheral-ERα effects, and directs GH secretion and IGF-I-binding proteins by complex mechanisms.

AB - Background: Estradiol (E2) stimulates GH and prolactin secretion and suppresses FSH secretion in postmenopausal women. Whether central nervous system (CNS) or pituitary mechanisms (or both) mediate such actions is not known. Objective: Our objective was to distinguish between hypothalamic and pituitary or peripheral (hepatic) actions of E2. Setting: This study was performed in an academic medical center. Design: This was a double-blind, prospectively randomized, placebo (Pl)-controlled study. Methods: The capability of a selective, noncompetitive, non-CNS permeant estrogen receptor (ER)-α antagonist, fulvestrant (FUL) to antagonize the effects of transdermal E 2 and Pl on GH, prolactin, and FSH secretion was assessed in 43 women (ages 50-80 yr) in a four parallel-cohort study. Each woman received four secretagogue infusions to stimulate GH secretion. IGF-I and its binding proteins were measured secondarily. Results: Administration of Pl/E2 increased GH and prolactin concentrations by 100%, and suppressed FSH concentrations by more than 50% (each P ≤ 0.004 compared with Pl/Pl). Treatment with FUL/E2 compared with Pl/E2 partially relieved estrogen's inhibition of FSH secretion (P = 0.041), without altering E2's stimulation of prolactin secretion. ANOVA further revealed that: 1) estrogen milieu (P = 0.014) and secretagogue type (P < 0.001) each determined GH concentrations; 2) FUL/Pl suppressed IGF-I concentrations (P < 0.001); 3) FUL abrogated estrogen's elevation of IGF binding protein-1 concentrations (P < 0.001); and 4) FUL did not oppose estrogen's suppression of IGF binding protein-3 concentrations (P < 0.001). Summary and Conclusions: Responses to a non-CNS permeant ERα antagonist indicate that E 2 inhibits FSH secretion in part via pituitary/peripheral ERα, drives prolactin output via nonpituitary/nonperipheral-ERα effects, and directs GH secretion and IGF-I-binding proteins by complex mechanisms.

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