Estrogen elevates the peak overnight production rate of acylated ghrelin.

Acylated ghrelin is the putatively bioactive GH secretagogue. Estradiol (E2) stimulates the synthesis rather than inhibits the metabolic clearance of acylated ghrelin. The study took place at an academic medical center. Healthy postmenopausal women participated. Interventions included prospectively randomized, double-blind separate-day iv infusions of saline or five graded doses of ghrelin in estrogen-deficient (n=12) and E2-supplemented (n=8) women. Metabolic clearance rate (MCR), volume of distribution, half-life, and secretion rate of acylated ghrelin were assessed. In pilot iv bolus ghrelin infusions, the median half-lives of acylated and total ghrelin were 21 and 36 min (P<0.01), MCRs 58 and 8.1 liters/kg.d (P<0.01), and volumes of distribution of 1.0 and 0.32 liters/kg (P<0.01), respectively. Transdermal E2 supplementation for 3 wk increased peak nighttime acylated ghrelin concentrations from 99+/-12 to 141+/-34 pg/ml (P=0.039). Exposure to E2 did not alter the linear relationships between 1) plasma acylated ghrelin concentration and ghrelin infusion rate (638+/-12 slope units), 2) MCR of acylated ghrelin and ghrelin infusion rate (10+/-2.5 slope units), and 3) MCR and plasma concentration of acylated ghrelin (0.017+/-0.004 slope units). These data predict peak nighttime production rates of acylated ghrelin of 3.8+/-0.9 (E2) and 1.9+/-0.2 (no E2) ng/kg.min (P=0.039). Acylated ghrelin has a multifold larger distribution volume and MCR than total ghrelin. An estrogenic milieu augments synthesis and/or acylation of ghrelin peptide without altering its MCR.