Regulation of basal, pulsatile, and entropic (patterned) modes of GH secretion in a putatively low-somatostatin milieu in women

Abstract

Somatostatin (SS) released by hypothalamic neurons inhibits GH exocytosis noncompetitively. Therefore, we postulated that attenuation of GH feedback-induced SS outflow would help to unmask covariates of endogenous secretagogue drive. To this end, 42 healthy pre- and postmenopausal women were randomly assigned to receive leuprolide plus estradiol (E2) or leuprolide plus placebo. A putatively low-SS milieu was imposed by l-arginine infusion. Deconvolution and regularity analyses were applied to 6-h GH concentration-time profiles. By two-way ANOVA, age negatively ( P < 0.001) and E2 positively ( P = 0.001) determined pulsatile GH secretion in the presumptively SS-deficient milieu ( P < 0.001). Comparable effects were exerted on the mass of GH secreted per burst per unit distribution volume (age P = 0.001, E2 P < 0.001, overall P < 0.001). E2 alone predicted basal (nonpulsatile) GH secretion ( P = 0.004). Stepwise forward-selection multivariate regression demonstrated that age ( P = 0.0017) and E2 ( P = 0.0002) together explained 46% of intersubject variability in pulsatile GH secretion ( P < 0.001) and fully replaced the negative univariate effect of abdominal visceral fat ( r2 = 0.32, P < 0.001). Moreover, age and E2 (but not AVF) interacted to supervise GH regularity ( P = 0.007). We conclude that age and E2 availability individually and together constitute primary predictors of basal, pulsatile, and patterned GH secretion in an inferentially feedback-silenced context in healthy women. Therefore, both factors must be considered in framing hypotheses of endogenous GH drive.