Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women

Abstract

Growth hormone (GH) secretion is subject to complex regulation. How pre- and postmenopausal age (PRE, POST), estradiol (E2) availability, and abdominal visceral fat (AVF) jointly affect peptidyl-secretagogue drive of GH secretion is not known. To this end, healthy PRE ( n = 20) and POST ( n = 22) women underwent a low- vs. high-E2clamp before receiving a continuous intravenous infusion of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP-2). According to analysis of covariance, PRE and POST women achieved age-independent hypo- and euestrogenemia under respective low- and high-E2clamps. All four of age ( P < 0.001), E2status ( P = 0.006), secretagogue type ( P < 0.001), and an age × peptide interaction ( P = 0.014) controlled pulsatile GH secretion. Independently of E2status, POST women had lower GH responses to both GHRH ( P = 0.028) and GHRP-2 ( P < 0.001) than PRE women. Independently of age, GHRP-2 was more stimulatory than GHRH during low E2( P = 0.011) and high E2( P < 0.001). Stepwise forward-selection multivariate analysis revealed that computerized tomographic estimates of AVF explained 22% of the variability in GHRH action ( P = 0.002), whereas age and E2together explained 60% of the variability in GHRP-2 drive ( P < 0.001). These data establish that age, estrogen status, and AVF are triple covariates of continuous peptide-secretagogue drive of pulsatile GH secretion in women. Each factor must be controlled for to allow valid comparisons of GH-axis activity.