Factors other than sex steroids modulate GHRH and GHRP-2 efficacies in men:
evaluation using a GnRH agonist/testosterone clamp.
Author(s): Veldhuis JD, Bowers CY.
Affiliation(s): Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical
Education, Clinical Translational Science Center, Mayo Clinic, Rochester,
Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Publication date & source: 2009, J Clin Endocrinol Metab. , 94(7):2544-50
BACKGROUND: Sex steroids are prominent regulators of pulsatile GH secretion.
Hypothesis: An experimentally controlled sex-steroid milieu will permit detection
of nonsteroidal factors that determine GH secretion.
SUBJECTS: Eleven young (age, 24 +/- 0.99 yr) and 11 older (64 +/- 2.4 yr) men
participated in the study.
LOCATION: The study was conducted at a tertiary medical center.
METHODS: The study consisted of GnRH-agonist down-regulation of the gonadal axis
followed by fixed-dose testosterone (T) replacement (leuprolide/T clamp) and
consecutive infusion of l-arginine and GHRH or GH-releasing peptide-2 (GHRP-2) to
quantify peptide-secretagogue efficacies.
OUTCOMES: The experimental leuprolide/T clamp yielded statistically
age-comparable total, bioavailable, and free T and estradiol (E(2))
concentrations. In this controlled milieu, sequential l-arginine/GHRH infusion
stimulated 1.4-fold more (P = 0.021) and l-arginine/GHRP-2 1.3-fold more (P =
0.045) GH release in young than older men. Abdominal visceral fat (AVF)
correlated negatively with both GHRH (P = 0.0006; R(2) = 0.39) and GHRP-2 (R(2) =
0.29) efficacy, whereas IGF-I positively predicted the same endpoints (R(2) =
0.25 to 0.30). In multivariate analysis, AVF emerged as a dominant negative
determinant of GHRH efficacy (P = 0.002; R(2) = 0.41) and IGF-I as a primary
positive determinant of GHRP-2 efficacy (P = 0.007; R(2) = 0.31).
CONCLUSION: During fixed T/E(2) availability, AVF contributes 41% of the
GH-response variability to maximal GHRH drive, whereas IGF-I accounts for 31% of
that for GHRP-2. Accordingly, a statistically equalized sex-steroid milieu
permits dissection of age-independent and T/E(2)-independent modulators of GHRH
and GHRP efficacy in men.
|