Studies on the mode of action of androgens in the neuroendocrine tissues

Experiments were performed to study the factors which might influence the activity of the 5α-reductase-3α-hydroxysteroid dehydrogenase system in the hypothalamus and in the anterior pituitary of male and female rats and to investigate the modulatory effects of a chronic treatment of testosterone (T) and of its 5α-reduced metabolites on LH and FSH secretion. Estradiol benzoate (EB), in a dose of 50ng/rat/day either for 7 or 14 days, did not have any effect on the enzymatic activities of the anterior pituitary and of the hypothalamus of castrated animals of both sexes and on the hypothalamus of castrated male rats. On the other hand the same dose significantly enhanced the testosterone conversion in the hypothalamus of castrated female rats. Higher dose of EB (5 μg/rat/day) proved able to bring back to precastration levels the 5α-reductase activity of the anterior pituitary of animals of both sexes in the 7-day schedule of administration and to further reduce it in the 14-day schedule. The same dose, while ineffective on the activity of the enzymes of the hypothalamus of the female, was highly active in suppressing it in the males. The treatment with 800 μg/rat for 5 days of prolactin did not modify the rate of conversion of T in the anterior pituitary and in the hypothalamus of normal male rats and in the gland of castrated males. A significant suppression of the enzymatic activities of the hypothalamus of castrated male rats was observed. T, dihydrotestosterone (DHT), 5α-androstan-3α, 17β-diol (3α-diol) were given, in a dose of 2 mg/day for 6 days, to castrated male and female rats in order to assess their inhibiting effect on LH and FSH secretion. DHT and 3α-diol were shown to be better suppressors of LH than T itself in both sexes. With regard to FSH no steroid was able to affect FSH release in castrated female and male rats with the exception of DHT which showed some inhibiting effect in males. The data suggests that EB and prolactin, by modifying the rate of conversion of T into DHT and 3α-diol, may modulate the effects of T at anterior pituitary and at hypothalamic levels. In addition they indicate that T probably exerts its negative feedback effect on gonadotropin secretion following its conversion into DHT and 3α-diol.