Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence

Abstract

The increase in GH production during the male adolescent growth spurt has been attributed to both androgen and estrogen receptor-mediated processes. To evaluate the role of endogenous estrogens in the control of GH secretion, we administered the estrogen receptor antagonist tamoxifen to 10 late pubertal males. Blood samples were obtained for GH determination at 10-min intervals on 2 occasions during the last 24 h of a 4-day course of either tamoxifen or placebo. Waveform-specific, multiple parameter deconvolution analysis was employed to assess GH secretory and elimination dynamics. Estrogen receptor blockade resulted in a significant (P < 0.05) diminution in mean 24-h serum GH concentrations, from 3.9 +/- 1.0 (placebo; mean +/- SEM) to 2.7 +/- 0.6 micrograms/L (tamoxifen). This was associated with a significant (P < 0.01) decline in the GH production rate [237 +/- 55 vs. 155 +/- 33 micrograms/L GH distribution volume (Lv).24 h]. Furthermore, this reduction in GH secretion was the result of significant decreases in both the maximal GH secretory rate (0.46 +/- 0.08 vs. 0.34 +/- 0.06 microgram/Lv.min; P < 0.01) and, to a smaller degree, GH secretory burst number (16 +/- 1 vs. 14 +/- 1/24 h; P < 0.05). There was also a trend toward reduced mass of GH secreted per burst (13.3 +/- 2.5 vs. 10.3 +/- 2.0 micrograms/Lv; P = 0.06). No significant alterations in either GH elimination t1/2 or GH secretory burst half-duration were observed during estrogen receptor antagonism. Tamoxifen treatment was associated with a significant (P < 0.05) decrease in plasma insulin-like growth factor-I concentrations. However, total and free testosterone, 17 beta-estradiol, insulin-like growth factor-binding protein-3, and pooled 24-h LH concentrations were not significantly changed by short term blockade of estrogen action. We postulate that endogenous estrogens play a facilitatory role in neuroendocrine control of the somatotropic axis during puberty in boys. Tamoxifen blocks this estrogen-dependent stimulation of GH secretion without altering the hormone elimination t1/2. Furthermore, we speculate that any stimulatory role of androgens on GH secretion is exerted primarily through the estrogen receptor after aromatization.