THE EFFECTS OF TESTOSTERONE AND DIHYDROTESTOSTERONE ON HYPOTHALAMIC REGULATION OF GROWTH-HORMONE SECRETION

Testosterone (T) administration to pubertal boys increases spontaneous GH secretion. It is not known whether this occurs via pituitary or hy pothalamic mechanisms. We evaluated the GH secretion of 12 boys, aged 13.67 +/- 0.37 yr (mean +/- SE), diagnosed with constitutional delay i n growth and adolescence. The evaluation was made both before and afte r 3 months of treatment with T or the nonaromatizable androgen, 5 alph a-dihydrotestosterone. Serum for determination of spontaneous GH secre tion was sampled every 20 min for 24 h. Pituitary responsiveness was a ssessed by the administration of GHRH with sampling of GH at intervals for the next 2 h. This was also done with pyridostigmine (PDS) pretre atment to assess the effects of somatostatin. The dose of androgen use d was 80 mg/m(2) month. All tests were then repeated during treatment. Spontaneous GH secretion was analyzed by the Cluster method. The resp onse to GHRH was measured as the area under the curve. Somatostatin ef fects were quantified as the difference in responsiveness between the two GHRH tests performed at each admission: one without prior PDS admi nistration and one in which somatostatin was blocked by PDS. Treatment with T increased mean spontaneous GH secretion from 2.25 +/- 0.34 mu g/L before treatment to 6.77 +/- 0.69 mu g/L (mean +/- SE; P < 0.001) and mean spontaneous peak height from 5.62 +/- 1.05 to 17.21 +/- 1.52 mu g/L (mean +/- SE; P < 0.001). No significant differences between pr etreatment and treatment evaluations for any spontaneous GH secretory parameters were seen in 5 alpha-dihydrotestosterone-treated patients, except that maximum peak height was decreased after treatment (P < 0.0 2). In T treated patients. the GHRH stimulation tests without prior PD S administration changed from 84.14 +/- 34.54 total mu g/L before to 1 02.3 +/- 35.82 total mu g/L (mean +/- SE; P = NS) after androgen treat ment. PDS pretreatment produced an increase in responsiveness to GHRH over the test without PDS pretreatment. This increase was 127.03 +/- 3 5.68 total mu g/L before T treatment; after T treatment, this increase was 78.38 +/- 57.6 total mu g/L (mean +/- SE; P = NS). T treatment, v ia an estrogen-dependent mechanism, caused increased GH pulse amplitud e, thereby increasing the mean serum GH concentration. This increase w as not the result of increased pituitary responsiveness or decreased s omatostatin tone. This indicates that T exerted its effect on GH via i ncreased GHRH pulse amplitude.