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 short-term 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.

The Role of Growth Hormone on Ovarian Functioning and Ovarian Angiogenesis

“…The effects of E2 on GH secretion after menopause were confirmed in a double-blind, controlled study in which plasma GH was analyzed before and after somatostatin infusion in healthy post-menopausal women treated with placebo or with an inhibitor of aromatase or a selective inhibitor of the E2 receptor. In this study a 1-h GH peak rebound after somatostatin infusion was clearly decreased during both estrogen-deprivation protocols (80). This study concluded that GH secretion after menopause depends on low levels of ovarian estrogens, and also confirms our previous postulate about that the interruption of somatostatin release induces the synthesis and secretion of GH via GHRH (9), and that sex steroids act on GH neuroregulation by inhibiting somatostatin secretion via alpha-2 noradrenergic pathways (9).…”

Is Growth Hormone Insufficiency the Missing Link Between Obesity, Male Gender, Age, and COVID‐19 Severity?

“…SARS‐CoV‐2 aggressiveness has been shown to be gender dependent and higher in males (1). Intriguingly, it is well known that GH secretion is, overall, greater in women of all ages than in men, and that sex steroids can on the one hand influence GH secretion and on the other hand alter IGF1 local synthesis in target tissues as well as the expression of the GH receptor (2). It has also been reported that the percentage of SARS‐CoV‐2 registered cases in China increased progressively with age, as it was 1% in 10‐ to 19‐year‐olds, 8% in 20‐ to 29‐year‐olds, and 87% in 30‐ to 79‐year‐olds (1).…”

Pituitary Growth Hormone Secretion and Cell Growth Hormone Production: Regulation of Their Secretion and Their Signaling Pathways

“…However, a recent randomized, doubleblind, controlled study, performed in 60 healthy postmenopausal women conclude that while there was a E2 decrease when giving anastrozole (an inhibitor of aromatase activity), but no changes in E2 levels were observed when fulvestrant (a selective estrogen receptor-α antagonist) was administered. In spite of it, GH rebound after SS infusion declined markedly during both estrogen-deprivation schedules, suggesting a previously unrecognized dependence of hypothalamic-pituitary GH regulation on low levels of endogenous estrogen during menopause [147].…”