Lack of an Effect of Dihydrotestosterone on Serum Luteinizing Hormone in Neonatal Female Rats

Abstract

Testosterone and its ring A reduced metabolite, dihydrotestosterone (DHT), lower gonadotrophin concentrations in weaned rats (Swerdloff, Walsh & Odell, 1972;Naftolin & Feder, 1973). While neonatally administered testosterone causes anovulatory sterility in adult female rats, similar treatment with DHT has no apparent effect upon central neuroendocrine programming (Brown-Grant, Munck, Naftolin & Sherwood, 1971;Whalen & Luttge, 1971), which raises the question of whether DHT can suppress gonadotrophins in the neonatal rat.In the first experiment, 5-day-old Sprague-Dawley-derived rats (Charles River Farms) were injected s.c. with 100 µg DHT propionate (DHTP), 100 µg testosterone propionate (TP, Eli Lilly & Co.) or the sesame oil diluent, and allowed to develop without further treatment. The injection volume was 25 µ . AU animals were weaned on day 20. Daily vaginal smears were carried out between days 60 and 75 and again from 140 to 150 days. Smears were classified as showing persistent oestrus (more than 70% of smears oestrus), persistent dioestrus (more than 70% of smears dioestrus), or vaginal cycles (less than 70% of smears oestrus, less than 70% of smears dioestrus) as previously described (Brown-Grant et al. 1971). There was no significant difference in the time of vaginal opening or in body weight at day 110 between any of the groups. The results of this experiment were similar to previous work, with 88% of TP-treated rats showing persistent oestrus at 140-155 days while oil-and DHTP-treated animals showed only zero and 3 % persistent oestrus, respectively.In two further experiments, 5-day-old female rats were treated as above. However, 6 h after injection the animals were exsanguinated by decapitation. In each group blood from four animals was pooled, centrifuged and assayed for serum luteinizing hormone (LH) as previously described (Naftolin & Feder, 1973). The error of the method was less than 5%. All samples from each experiment were measured in duplicate in the same assay.Although TP significantly suppressed the serum LH level in 5-day-old female rats by 6 h after injection, no effect of DHTP could be demonstrated in either experiment (Fig. 1).In addition to confirming previous work regarding the ineffectiveness of neonatally administered DHT, the present study shows DHT to be ineffective in lowering the level of LH in the newborn female rat. The proposal that the organizing effect of neonatally administered testosterone is dependent upon its conversion to oestrogen has been based upon the demonstra¬ tion of aromatization by the anterior hypothalamus and limbic system in human foetuses (Naftolin, Ryan & Petro, 1971) and perinatal male and female rats (Reddy, Naftolin & Ryan, 1974). This is supported by the potency of oestrogens for causing anovulatory sterility (Gorski, 1963), and the blockade of the testosterone effect by pretreatment with MER-25, an antioestrogen (McDonald & Doughty, 1973/4). The present study showing the lack of an effect of neonatally administered DHT on serum LH seems further to su...