Modulating effects of progesterone on spontaneous nocturnal and ghrelin-induced GH secretion in postmenopausal women

Background: Oral administration of estradiol (E₂) generally increases GH secretion in postmenopausal women. Oral administration of E₂ is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E₂ may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied. We hypothesized that moderately increased serum E₂ levels stimulate GH and that P4 modulates E₂-stimulated GH secretion. Study Design: Four parallel groups of randomly assigned postmenopausal women (n = 40). Treatments were saline placebo and oral placebo, saline placebo and oral micronized P4 (3 200 mg/d IM), E₂ (5 mg IM) and oral placebo, and E₂ IM and oral micronized P4. Outcome measures were overnight GH secretion (10 hours), stimulated (ghrelin, 0.3 g/kg IV bolus) GH secretion, and CT-estimated visceral fat. Results: Intramuscular E₂ administration did not alter nocturnal and ghrelin-stimulated GH secretion. Nocturnal GH secretion was not changed by P4 administration. However, P4 diminished ghrelin-stimulated pulsatile GH release with or without E₂ (average, 7.20 6 2.14 and 9.58 6 1.97 g/L/2 h, respectively; P = 0.045). Respective outcomes for mean GH concentrations and GH peak amplitudes were 0.97 6 0.31 and 1.52 g/L 6 0.29 (P = 0.025) and 2.76 6 1.04 and 3.95 g/L 6 0.90 (P = 0.031). Ghrelin-stimulated GH secretion correlated negatively with P4 concentration with or without correction for visceral fat area in the regression equation (R = 0.49, P = 0.04, = 20.040 6 0.016). Conclusions: Low-range physiological E₂ concentrations do not affect spontaneous or ghrelin-stimulated pulsatile GH secretion. Conversely, P4 inhibits ghrelin-stimulated GH secretion in a concentration-dependent fashion. The mechanistic aspects and physiological significance of natural P4's regulation of ghrelin-evoked GH secretion require further study.