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 capsules with lengths of 2, 4, 8 or 16 cm, and control animals received empty capsules (eight per treatment). The treatments increased serum T up to 3-fold of control levels. In intact animals, the 2-8 cm capsules suppressed pituitary follicle-stimulating hormone-beta (FSHbeta) mRNA contents by 40-50% (p < 0.01), but 16 cm of T returned the levels back to 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 than in intact animals receiving the same T dose. Pituitary luteinizing hormone-beta (LHbeta) mRNA displayed a dose-dependent suppression in response to T, to 32-35% of controls (p < 0.01) with the 8 and 16 cm capsules. Castration increased this message 10-fold, and additional T treatment 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 common-alpha contents, in comparison to the other doses, to 54% of controls (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 contents of intact and castrated rats also displayed a biphasic T response: suppression by low doses and recovery by higher doses. Despite the clear stimulation in the gene expression and pituitary content of FSH with 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 intact 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 the levels of inhibin subunit mRNAs by T treatment. The weight of the testis was reduced by 2-8 cm T treatments (p < 0.01), but 16 cm of T reversed the weight to control level. In conclusion, T treatment has a biphasic effect on the gene expression and synthesis of FSH in intact and castrated male rats. However, FSH secretion is not increased by high doses of T, evidently due to suppressed gonadotropin-releasing hormone (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.