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

Background: Estradiol (E(2)) 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)-alpha antagonist, fulvestrant (FUL) to antagonize the effects of transdermal E2 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
Summary And Conclusions: Responses to a non-CNS permeant ERalpha antagonist indicate that E2 inhibits FSH secretion in part via pituitary/peripheral ERalpha, drives prolactin output via nonpituitary/nonperipheral-ERalpha effects, and directs GH secretion and IGF-I-binding proteins by complex mechanisms.