Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women.
Growth hormone (GH) secretion is subject to complex regulation. How pre- and postmenopausal age (PRE, POST), estradiol (E(2)) 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-E(2) clamp 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-E(2) clamps. All four of age (P < 0.001), E(2) status (P = 0.006), secretagogue type (P < 0.001), and an age x peptide interaction (P = 0.014) controlled pulsatile GH secretion. Independently of E(2) status, 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 E(2) (P = 0.011) and high E(2) (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 E(2) together 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.
Veldhuis
Johannes D
JD
Departments of Internal Medicine, Endocrine Research Unit, Clinical Translational Research Unit, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, Minnesota, USA. veldhuis.johannes@mayo.edu
Hudson
Susan B
SB
Erickson
Dana
D
Bailey
Joy N
JN
Reynolds
George Ann
GA
Bowers
Cyril Y
CY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006262:Health; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000502:physiology*; D016729:Leuprolide / Q000008:administration & dosage; D008875:Middle Aged; D010919:Placebos; D011673:Pulsatile Flow / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D010919:Placebos; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016729:Leuprolide