Bimodal Effects of Luteinizing Hormone and Role of Androgens in Modifying Superovulatory Responses of Rats to Infusion with Purified Porcine Follicle-Stimulating Hormone1

Publisher Website
Google Scholar
Abstract
Prepubertal (28-30 days old) female rats were infused s.c. over a 60-h period with a purified porcine pituitary follicle-stimulating hormone (FSH) preparation having FSH specific activity 8.4 times that of NIH-FSH-S1 and luteinizing hormone (LH) specific activity < 0.005 times that of NIH-LH-S1, based on radioreceptor assays. When the FSH infusion rate of this preparation was increased over the range of 0.5-2 units/day (mg NIH-FSH-S1 equivalent), an all-or-none response was observed, with the threshold dose for superovulation being between 1 and 2 units/day. Eleven of twelve rats receiving the 2 units/day dose ovulated a mean .+-. SEM of 67 .+-. 8 oocytes on the morning of the third day after the beginning FSH infusion. Addition of human chorionic gonadotrophin (hCG), as a source of LH activity, to a subthreshol (1 U/day) FSH infusion rate resulted in 20% of rats ovulating at an hCG dosage of 50 mIU/day; increasing the hCG infusion to 20 mIU/day concomitant with a subthreshold FSH infusion rate increased ovulation rate to a mean of 69 .+-. 8/rat, with 100% of rats ovulating. To determine the effect of varying both FSH infusion rates and LH:FSH ratios, FSH was infused at several rates, with hCG added to give varying hCG:FSH ratios for each FSH infusion rate. Administration of hCG alone was ineffective in causing ovulation except at the highest infusion rates. Adding hCG to FSH to reach a ratio of 0.2 IU hCG/U FSH significantly increased the superovulatory response to an intermediate, 1 U/day FSH dose, but not to the low, 0.5 U/day dose. A threefold increase in ratio to 0.66 IU hCG/U FSH increased the ovulatory response to the lowest FSH dose (0.5 U/day), caused no change in the response to the intermediate FSH dose, and significantly decreased the response to the highest FSH dose (2 U/day). A further threefold increase in hCG:FSH ratio to 2 IU/U significantly decreased the responses to all three FSH doses. Administration of the androgen antagonist, hydroxyflutamide (5 mg/day, s.c.), to rats infused with 1 U/day FSH supplemented with varying doses of hCG was without significant effect on ovulatory responses at hCG:FSH ratios of 0 and 0.2 IU hCG/U FSH, but completely reversed the inhibition of ovulation seen at an hCG:FSH ratio of 2 IU/U. From the results of the research, it is evident that maximal superovulatory responses in FSH-infused rats occur over an optimal range of LH:FSH activity ratios, with decreased responses resulting at inadequate or excessive LH:FSH ratios. The ability of an anti-androgen to overcome the inhibitory effect of high LH:FSH ratios suggests that androgen-mediated follicular atresia contributes to the reduced ovulation rate resulting from excessive LH stimulation during follicular growth.