Activation of the somatotropic axis by testosterone in adult males: evidence for the role of aromatization.
To determine whether testosterone modulates the somatotropic axis in adult males, we compared 24-h GH secretion (from 20-min sampling, using Cluster analysis) and insulin-like growth factor-I (IGF-I) levels of five hypogonadal men (aged 20-32 yr) with those of six normal men (aged 21-27 yr), and examined the effects of testosterone replacement (testosterone enanthate 250 mg im monthly). To elucidate whether the action of testosterone on the somatotropic axis is direct, or requires the aromatization of testosterone to estradiol, we also examined the effects of the nonsteroidal antiestrogen, tamoxifen (20 mg/day for 3 weeks), on 24-h GH secretion and IGF-I levels in the normal men and in four of the hypogonadal men during concurrent testosterone treatment. Compared to the normal men, the hypogonadal men had significantly reduced mean GH pulse amplitude (3.1 +/- 0.6 vs. 8.4 +/- 1.7 micrograms/L, P < 0.05), but not pulse frequency. Testosterone treatment resulted in a significant increase in 24-h mean serum GH (0.7 +/- 0.2 to 1.4 +/- 0.2 micrograms/L, P < 0.05), mean GH pulse amplitude (3.1 +/- 0.6 to 5.2 +/- 0.8 micrograms/L, P < 0.01) and serum IGF-I (0.9 +/- 0.1 to 1.1 +/- 0.1 U/mL, P < 0.05). In the normal men, tamoxifen significantly reduced 24-h mean serum GH (1.1 +/- 0.3 to 0.5 +/- 0.1 micrograms/L, P < 0.05), mean GH pulse amplitude (8.4 +/- 1.7 to 4.7 +/- 0.4 micrograms/L, P < 0.05), and serum IGF-I (1.0 +/- 0.1 to 0.7 +/- 0.1 U/mL, P < 0.001). In the hypogonadal men on testosterone replacement, tamoxifen lowered 24-h mean serum GH (1.3 +/- 0.2 to 0.6 +/- 0.2 micrograms/L, P < 0.01), mean GH pulse amplitude (5.5 +/- 1.0 to 2.4 +/- 0.8 micrograms/L, P < 0.01), and serum IGF-I (1.2 +/- 0.1 to 0.8 +/- 0.1 U/mL, P < 0.05). We conclude that testosterone plays an important role in the modulation of the male somatotropic axis in adulthood, as appears to be the case in puberty, and that this effect is partly dependent on the aromatization of testosterone to estradiol.
Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia.
A J
AJ
Weissberger
K K
KK
Ho
D000328:Adult; D013006:Growth Hormone / Q000097:blood / Q000502:physiology*; D006801:Humans; D007006:Hypogonadism / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D012016:Reference Values; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D013629:Tamoxifen; D013739:Testosterone; D013006:Growth Hormone