ESTROGEN-RECEPTOR BLOCKADE WITH TAMOXIFEN DIMINISHES GROWTH-HORMONE SECRETION IN BOYS - EVIDENCE FOR A STIMULATORY ROLE OF ENDOGENOUS ESTROGENS DURING MALE ADOLESCENCE

The increase in GK production during the male adolescent growth spurt has been attributed to both androgen and estrogen receptor-mediated pr ocesses. To evaluate the role of endogenous estrogens in the control o f GH secretion, we administered the estrogen receptor antagonist tamox ifen to 10 late pubertal males. Blood samples were obtained for GH det ermination at 10-min intervals on 2 occasions during the last 24 h of a 4-day course of either tamoxifen or placebo. Waveform-specific, mult iple parameter deconvolution analysis was employed to assess GH secret ory and elimination dynamics. Estrogen receptor blockade resulted in a significant (P < 0.05) diminution in mean 24-h serum GH concentration s, from 3.9 +/- 1.0 (placebo; mean +/- SEM) to 2.7 +/- 0.6 mu g/L (tam oxifen). This was associated with a significant (P < 0.01) decline in the GH production rate [237 +/- 55 vs. 155 +/- 33 mu g/L GH distributi on volume (L(v)).24 h]. Furthermore, this reduction in GH secretion wa s the result of significant decreases in both the maximal GH secretory rate (0.46 +/- 0.08 us. 0.34 +/- 0.06 mu g/L(v) min; P < 0.01) and, t o a smaller degree, GH secretory burst number (16 +/- 1 us. 14 +/- 1/2 4 h; P < 0.05). There was also a trend toward reduced mass of GH secre ted per burst (13.3 +/- 2.5 vs. 10.3 +/- 2.0 mu g/L(v); P = 0.06). No significant alterations in either GH elimination t(1/2) or GH secretor y burst half-duration were observed during estrogen receptor antagonis m. Tamoxifen treatment was associated with a significant (P < 0.05) de crease in plasma insulin-like growth factor-I concentrations. However, total and free testosterone, 17 beta-estradiol, insulin-like growth f actor-binding protein-3, and pooled 24-h LH concentrations were not si gnificantly changed by short term blockade of estrogen action. We post ulate that endogenous estrogens play a facilitatory role in neuroendoc rine control of the somatotropic axis during puberty in boys. Tamoxife n blocks this estrogen-dependent stimulation of GH secretion without a ltering the hormone elimination t(1/2). Furthermore, we speculate that any stimulatory role of androgens on GH secretion is exerted primaril y through the estrogen receptor after aromatization.