Submitted on April 6, 2009
Revised on May 26, 2009
Accepted on May 26, 2009
Relative Effects of Estrogen, Age and Visceral Fat on Pulsatile Growth-Hormone Secretion in Healthy Women
Johannes D. Veldhuis1*, Susan A. Hudson1, Dana Erickson1, Joy N. Bailey1, George Ann Reynolds2, and Cyril Y. Bowers3
1 Mayo School of Graduate Medical Education, Center for Translational Science Activities
2 Tulane Medical Center
3 Tulane University Health Sciences Center
* To whom correspondence should be addressed. E-mail: veldhuis.johannes{at}mayo.edu.
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-E2 clamp before receiving a continuous iv infusion of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP-2). According to analysis of covariance (ANCOVA), PRE and POST women achieved age-independent hypo- and euestrogenemia under respective low- and high-E2 clamps. All four of age (P < 0.001), E2 status (P = 0.006), secretagogue type (P < 0.001), and an age x peptide interaction (P = 0.014) controlled pulsatile GH secretion. Independently of E2 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 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 E2 together explained 60% of the variability in GHRP-2 drive (P < 0.001). Conclusion. These data establish that age, estrogen status and AVF are triple covariates of continuous peptide-secretagogue drive of pulsatile GH secretion in women.
