Testosterone blunts feedback inhibition of growth hormone secretion by experimentally elevated insulin-like growth factor-I concentrations.
The present study tests the hypothesis that a high dose of testosterone (Te) drives GH and IGF-I production, in part, by blunting autonegative feedback by the end-product peptide. To this end, we infused saline or recombinant human IGF-I (10 microg/kg.h iv for 6 h) in seven healthy men ages 51-72 yr after administration of placebo (Pl) and Te in randomized order. GH release was quantitated fasting before and after injection of GHRH (1 microg/kg). Statistical analyses disclosed that Te vs. Pl: 1) increased the mean concentration of GH from 0.15 +/- 0.045 to 0.48 +/- 0.11 microg/liter (P = 0.007) and IGF-I from 108 +/- 5.0 to 124 +/- 4.1 (P = 0.047) without altering GHRH-induced GH release; 2) elevated the GH nadir from 0.13 +/- 0.03 to 0.23 +/- 0.06 microg/liter (P < 0.05) in the control session and from 0.06 +/- 0.02 to 0.14 +/- 0.04 microg/liter (P = 0.038) during IGF-I infusion; 3) augmented GHRH-stimulated GH release from 3.0 +/- 0.56 (Pl) to 3.7 +/- 0.52 microg/liter (Te) (P < 0.05) during IGF-I infusion; and 4) did not influence estimated IGF-I kinetics. In summary, supplementation of a high dose of Te in middle-aged and older men attenuates IGF-I feedback-dependent inhibition of nadir and peak GH secretion. Both effects of Te differ from those reported recently for estradiol in postmenopausal women. Accordingly, we postulate that Te and estrogen modulate IGF-I negative feedback differentially.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Mayo School of Graduate Medical Education, General Clinical Research Center, 200 First Street Southwest, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Anderson
Stacey M
SM
Iranmanesh
Ali
A
Bowers
Cyril Y
CY
D000368:Aged; D000375:Aging / Q000378:metabolism; D000728:Androgens / Q000008:administration & dosage*; D004703:Endocrine System / Q000187:drug effects*; D025461:Feedback, Physiological / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D013739:Testosterone / Q000008:administration & dosage*
D000728:Androgens; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone