Effects of Testosterone, Dihydrotestosterone, and Estradiol on the Impaired Prolactin Response to Metoclopramide in the Castrated Rat

Abstract

This study was designed to assess the effect of three testicular steroids, testosterone, dihydrotestosterone, and estradiol, on PRL secretion in castrated rats. This has been done by evaluating the effect of androgens and estrogens and their antagonists, alone or in combination, on metoclopramide (MET)-induced PRL secretion in the castrated male rat. Ventral prostate and seminal vesicles retained normal weight after treatment of castrated rats with testosterone propionate (TP) and dihydrotestosterone (DHT). This effect was partially antagonized by the antiandrogen cyproterone acetate (CA) which in itself had no effect. TP, as well as DHT and EB, prevented the rise of plasma and pituitary LH and plasma FSH consequent to castration. CA partially blunted the TP and completely blocked the DHT effect, indicating that it acts as an antiandrogen. Nafoxidine hydrochloride (NH) antagonized the effect of EB, but not of TP on gonadotropins. This indicates that in combination with EB, NH acts as an antiestrogen.

The PRL response to MET was significantly reduced in castrated rats (P<0.001, compared with controls). Administration of TP, DHT, and CA partially restored PRL secretion to normal. When castrated rats received TP in combination with CA, a normal response was achieved. However, the DHT/CA combination only partially restored the PRL response.

Administration of NH alone also partially restored PRL secretion to normal. When castrated rats received TP in combination with NH, their response was indistinguishable from controls. EB produced a markedly exaggerated response, but when given in combination with NH, the antiestrogen inhibited the effect of EB on the PRL response to MET.

It is concluded that TP, like DHT, while maintaining the weight of the accessory sex organs, only partially restored the PRL response. A similar effect on PRL secretion was observed with CA, which did not affect accessory sex organ weight. When NH was administered alone, it was a weak estrogen agonist. In combination with EB, it acted as an antiestrogen and attenuated the effect of EB on the PRL response to MET. In contrast, when given with TP, there was a synergistic effect on the PRL response. This suggests that testosterone and dihydrotestosterone are not solely responsible for the maintenance of PRL secretion in the male rat and that other testicular products are presumably also required.