BIPHASIC EFFECT OF EXOGENOUS TESTOSTERONE ON FOLLICLE-STIMULATING-HORMONE GENE-EXPRESSION AND SYNTHESIS IN THE MALE-RAT

Effects of 2-week treatments with increasing doses of testosterone (T) on gonadotropin gene expression and secretion were studied in intact and acutely castrated male rats. T was administered in silastic capsul es with lengths of 2, 4, 8 or 16 cm, and control animals received empt y capsules (eight per treatment). The treatments increased serum T up to 3-fold of control levels. In intact animals, the 2-8 cm capsules su ppressed pituitary follicle-stimulating hormone-beta (FSHbeta) mRNA co ntents by 40-50% (p < 0.01), but 16 cm of T returned the levels back t o control range. Castration alone increased the FSHbeta mRNA level 2.3 -fold (p < 0.01) and, after T treatment, the FSHbeta message returned to control levels indistinguishable from intact controls but higher th an in intact animals receiving the same T dose. Pituitary luteinizing hormone-beta (LHbeta) mRNA displayed a dose-dependent suppression in r esponse to T, to 32-35% of controls (p < 0.01) with the 8 and 16 cm ca psules. Castration increased this message 10-fold, and additional T tr eatment suppressed the levels to the range of T-treated intact animals . Pituitary common-alpha mRNA decreased to 30-31% of controls by 2, 4 and 8 cm of T (p < 0.01), but the highest dose of T increased the comm on-alpha contents, in comparison to the other doses, to 54% of control s (p < 0.01). Castration alone increased the common-alpha contents 4.4 -fold, and there was a dose-dependent suppression of this parameter by T down to the range of T-treated intact rats. The pituitary FSH conte nts of intact and castrated rats also displayed a biphasic T response: suppression by low doses and recovery by higher doses. Despite the cl ear stimulation in the gene expression and pituitary content of FSH wi th the highest T dose, no evidence for increased secretion was found. A monophasic dose-dependent suppression of pituitary LH by T occurred in intact and castrated rats. Serum LH decreased with all T doses in i ntact and castrated animals (p < 0.01), and the 8-fold increase after castration was reversed with all T doses (p < 0.01). The T treatments had no effect on serum inhibin levels, neither were there changes in t he levels of inhibin subunit mRNAs by T treatment. The weight of the t estis was reduced by 2-8 cm T treatments (p < 0.01), but 16 cm of T re versed the weight to control level. In conclusion, T treatment has a b iphasic effect on the gene expression and synthesis of FSH in intact a nd castrated male rats. However, FSH secretion is not increased by hig h doses of T, evidently due to suppressed gonadotropin-releasing hormo ne (GnRH) secretion. Only negative effects of the different doses of T were observed on LH gene expression, synthesis and secretion. Inhibin gene expression and secretion were not affected by T.