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Induction of luteolysis by dihydrotestosterone in the pregnant rat
Abstract:
A dihydrotestosterone (DHT) pellet (4 mg) inserted under each ovarian bursa on day 9 of pregnancy induced within 24 h, a 40% decline in serum progesterone (P) concentrations in rats; a further reduction was observed on days 12 and 15. Although P levels were significantly reduced by DHT treatment, fetuses remained alive on day 12. However, by day 15, complete abortion occurred in 75% of the rats, indicating that a decline in P secretion precedes abortion, To further determine whether the abortifacient action of DHT was due to its luteolytic effect, 20-cm DHT capsules were implanted subcutaneously in ovariectomized rats treated with 4 mg P and 0.5 micrograms of estradiol (E). Control rats were sham-operated and treated with empty capsules. DHT treatment induced complete abortion by day 15 only in rats with ovaries present, further indicating that DHT was not directly detrimental to the fetuses but acted on the ovaries to induce luteolysis. When DHT treatment was started on day 12, no luteolytic effect was detectable. To determine whether the effect of DHT was mediated by either a decrease in the ovarian production of E, a decline in luteal cell content of luteinizing hormone (LH) receptors or both, testosterone (T) levels in the peripheral circulation and E and P concentrations in the ovarian vein were measured on day 15 in rats implanted with two DHT pellets under the ovarian bursa on day 9. Luteal content of LH receptors was also measured on day 12 in similarly treated rats. DHT treatment had no effect on serum levels or on ovarian vein concentration of E, but induced a significant decrease in the ovarian vein levels of P. DHT also did not depress LH receptor content in corpora lutea. DHT levels in the ovaries increase significantly between days 18 and 22 of pregnancy, concomitant with the cessation of corpus luteum function. These results indicate that DHT possesses a potent luteolytic activity and could be involved in the luteolytic process in the pregnant rat.