Endogenous estrogen regulates somatostatin-induced rebound GH secretion in postmenopausal women

Abstract

Background: Systemic concentrations of T, estradiol (E2), GH, IGF-1, and IGF binding protein-3 decline in healthy aging individuals. Conversely, T and E2 stimulate GH and IGF-1 production in hypogonadal patients. Hypothesis: Because E2 stimulates GH secretion, putatively via the nuclear estrogen receptor-α and E2 and GH fall with menopause, we postulated that diminished endogenous E2 contributes to low GH output in older women. Location: The study was conducted at the Mayo Center for Clinical and Translational Science. Study Design: This was a randomized, double-blind, controlled study in 60 healthy postmenopausal women treated with the following: 1) double placebo; 2) anastrozole, a potent inhibitor of aromatase-enzyme activity, which mediates E2 synthesis from T; and/or 3) fulvestrant, a selective estrogen receptor-α antagonist. Methods: GH pulse generation was quantified by frequent GH sampling before and after shortterm iv somatostatin infusion, thought to induce hypothalamic GHRH-mediated rebound-like GH secretion. Results: On anastrozole, E2 fell from 3.1±0.35 pg/mL to 0.36±0.04 pg/mL, and estrone from 13± 1.4 pg/mL to 1.9 ± 0.01 pg/mL (P < .001) by mass spectrometry. Estrogen values were unchanged by fulvestrant. T concentrations did not change. One-hour peak GH rebound after somatostatin infusion declined markedly during both estrogen-deprivation schedules P< .001).Mean(150 min) maximal GH rebound decreased comparably (P < .001). Measures of GH rebound correlated negatively with computed tomography-estimated abdominal visceral fat (all P < .05). Conclusion: These data suggest a previously unrecognized dependence of hypothalamo-pituitary GH regulation on low levels of endogenous estrogen after menopause.