Regulation of basal, pulsatile, and entropic (patterned) modes of GH secretion in a putatively low-somatostatin milieu in women.
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 (E(2)) 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 E(2) 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, E(2) P < 0.001, overall P < 0.001). E(2) alone predicted basal (nonpulsatile) GH secretion (P = 0.004). Stepwise forward-selection multivariate regression demonstrated that age (P = 0.0017) and E(2) (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 (r(2) = 0.32, P < 0.001). Moreover, age and E(2) (but not AVF) interacted to supervise GH regularity (P = 0.007). We conclude that age and E(2) 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.
Veldhuis
Johannes D
JD
Departments of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Hudson
Susan A
SA
Bailey
Joy N
JN
Erickson
Dana
D
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001481:Basal Metabolism / Q000187:drug effects / Q000502:physiology*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019277:Entropy; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D010919:Placebos; D011673:Pulsatile Flow / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000097:blood* / Q000378:metabolism; D055815:Young Adult
D003692:Delayed-Action Preparations; D010919:Placebos; D019382:Human Growth Hormone; D004958:Estradiol; D013004:Somatostatin; D016729:Leuprolide