Effects of in vivo dihydrotestosterone treatment on changes in nocturnal surge of prolactin, luteal ultrastructure and P-450 SCC mRNA and protein content in pregnant rats

Abstract

We have demonstrated previously that the administration of dihydrotestosterone (DHT) decreases plasma progesterone levels within 24 h and thus, results in abortion during the first half of pregnancy (Am. J. Physiol. 241 (1981) E444–E448). The purpose of this study was to determine (a) if the administration of DHT suppresses plasma prolactin levels or its nocturnal surge within 24 h after the treatment, (b) how soon after the commencement of treatment do the concentrations of DHT increase and progesterone levels decrease in the circulation, (c) the ultrastructural changes that occur in corpora lutea, and (d) the changes in luteal P-450 side-chain cleavage ( P-450 SCC) enzyme and mRNA content upon DHT treatment. Within 24 h after the commencement of DHT treatment, the nocturnal surge of prolactin, detected in both groups on day 10 at 03.30 h, was inhibited in DHT-treated rats as compared to controls. The non-surge levels of prolactin at 05.00 and 06.00 h were not different between groups. The intraovarian DHT pellet increased plasma levels of the steroid 3-fold within 2 h (blood samples were taken at 2-hourly intervals) when compared to controls. By 24 h DHT levels were decreased but were still higher than controls. Plasma progesterone levels began to fall 6 h after the commencement of treatment. Luteal tissue from animals treated with DHT appeared steroidogenic, and contained more lipid droplets than controls. No changes in mitochondrial structure or number were observed. Although the amount of luteal P-450 SCC mRNA was lower in the DHT-treated rats compared to control rats, this decrease was not associated with a decline in P-450 scc protein content within 24 h after DHT treatment. These data suggest that exogenous administration of DHT in pregnant rats results in acute high levels of plasma DHT leading to decreased plasma progesterone levels. The decline in plasma progesterone may be due to decreased cholesterol transport to the mitochondria or to decreased esterase activity. The lower progesterone levels, in turn, may lead to inhibition of the nocturnal prolactin surge. This study provides new information and insight into the abortifacient mechanism of DHT.