TY - JOUR
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.
N1 - Funding Information:
This work was supported in part via the Center for Translational Science Activities Grant no. 1 UL 1 RR024150 to the Mayo Clinic and Foundation from the National Center for Research Resources (Rockville, MD), and Grants R01 NIA AG029362, R21 DK072095, DK063609, RR019991 from the National Institutes of Health (Bethesda, MD).
PY - 2008/3
Y1 - 2008/3
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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U2 - 10.1210/jc.2007-1322
DO - 10.1210/jc.2007-1322
M3 - Article
C2 - 18089703
AN - SCOPUS:40849113045
SN - 0021-972X
VL - 93
SP - 951
EP - 958
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -