Effects of Prolactin on Androgen Metabolism in Androgen Target Tissues of Immature Rats*

Abstract
Testosterone metabolism in androgen target tissues of immature Wistar male rats was studied after the injection of ovine PRL (oPRL) or after changes in PRL levels induced by the administration of dopaminergic agonists or antagonists. Treatment with oPRL (500 μg/rat-day) for 10 days, starting on day 30 of age, caused a significant increase in testes and sex accessory organ weights and a concomitant augmentation in prostatic 5α-reductase activity. This effect, however, was not observed in epididymis and seminiferous tubules (ST). Daily administration of bromocriptine (3 mg/kg BW) using the same injection schedule suppressed endogenous PRL without altering serum LH levels. Testis and sex accessory organ weights and serum 5α-androstane-3α,17β-diol levels were reduced in the animals treated with this dopaminergic agonist. These changes were associated with a significant decrease in 5α-reductase activity in both prostate gland and ST. Treatment with the dopaminergic antagonist sulpiride (43 mg/kg BW) during the same period induced a 4-fold increase in serum PRL levels, whereas LH levels remained unaltered. Although serum concentrations of testosterone (plus dihydrotestosterone) and 5α-androstane-3α,17β-diol were significantly higher in sulpiride-treated rats, no significant changes in testis and sex accessory organ weights were detected in these animals. Sulpiride was unable to stimulate A4-5α-reductase activity in the prostate gland. Treatment with sulpiride or bromocriptine caused a significant increase in the 3α-hydroxysteroid dehydrogenase (3α-HDH) activity in ST. This effect was concomitantly seen in the ST and epididymides of 25-day-old rats after bromocriptine administration for 5 days. Another dopaminergic antagonist, pimozide, was also able to induce a similar increase in 3α-HDH activity in the ST and epididymis, even though chronic administration of this drug produced a significant decrease in serum PRL levels. The diminution in enzyme activity observed after the suppression of endogenous PRL levels by bromocriptine suggests that this hormone is involved in the control of Δ4-5α-reductase in the prostate and ST. However, induction of similar changes in the 3α-HDH activity by two dopaminergic agents with opposite effects on plasma PRL levels indicates the possibility of direct actions of these drugs on androgen target tissues.