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The effects of 3-week treatment with increasing doses of epitestosterone (ET) on gonadotrophin gene expression and secretion, on testosterone and 5-dihydrotestosterone (DHT) levels, and on the weight of testes and prostates, were studied in intact adult male rats. The hormones were delivered by means of silastic capsules of different lengths filled with the steroid. One group of rats received testosterone (T) instead of ET, to compare the results with previous studies concerning the testosterone effect. The controls were given capsules with glucose only. Treatment with ET, as well as with T, significantly reduced the weights of prostates. When the data from ET-treated rats and controls were combined, a significant negative correlation (P<0·001) was found between the weight of prostates and serum ET. T, in contrast to ET, also decreased significantly the weights of testes. ET treatment caused a significant reduction of serum T levels but only an insignificant decline of DHT levels, independent of the dose. Serum and pituitary (p) luteinizing hormone (LH) levels in the ET-treated rats did not change. Pituitary mRNA contents for the βLH subunit (βLH-mRNA) showed a dose-dependent significant increase, up to 170% (P<0·01), with ET treatment. pFSH decreased with the lowest ET (2 cm) dose (P<0·05), but no change was observed with the other doses. The mRNA for the common -subunit also increased with the ET load. In conclusion, ET acts at several sites in the regulation of gonadotrophin formation and release. It enhances the steady-state mRNA levels of both gonadotrophins in the pituitary. At the same time, ET may act directly in the pituitary by inhibition of post-transcriptional events in LH synthesis. A direct inhibitory effect of ET at the hypothalamic level is also possible. The circulating levels of both gonadotrophins are thus the result of these composite effects.

Journal of Endocrinology (1994) 143, 353–358

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