Effects of Luteinizing Hormone on Superovulatory and Steroidogenic Responses of Rat Ovaries to Infusion with Follicle-Stimulating Hormone1

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Abstract
Immature female rats were infused s.c. continuously over a 60-h period with a partially purified procine pituitary follicle-stimulating hormone (FSH) preparation having FSH activity 4.2 .times. NIH-FSH-S1 and luteinizing hormone (LH) activity 0.022 .times. NIH-LH-S1. High rates of superovulation were observed in rats receiving 1 U FSH/day, with 69 .+-. 11 oocytes/rat recovered as cumulus-enclosed oocytes from oviducts an Day 1 (equivalent to the day of estrus). Addition of LH to the FSH, at dosages equivalent to 2.5-100 .mu.g/day NIH-LH-S1 equivalent (2.5-100 mU) resulted in a dose-related inhibition of superovulation, reaching a nadir of 15 .+-. 7 oocytes recovered from rats receiving 50 mU LH/day together with 1 U FSH/day. At the two highest LH doses, 50 and 100 mU/day, ovulation was advanced so that 12 .+-. 3 and 15 .+-. 4 oocytes, respectively, were recovered from oviducts of these rats flushed on the morning of Day 0, compared to none in rats infused with FSH alone. Ovarian steroid concentrations (ng/mg) observed on the morning of Day 0 in rats infused with FSH alone were progesterone, 0.50 .+-. 0.13; testosterone, 0.16 .+-. 0.08; androstenedione, 0.06; and estradiol, 0.23 .+-. 0.05. On the morning of Day 1, ovarian progesterone concentrations in rats infused with FSH alone had risen to 3.30 .+-. 0.33 ng/mg, whereas concentrations of testosterone, androstenedione, and estradiol, had fallen to essentially undetectable levels. Addition of LH to the FSH infusion resulted in dose-related increases, on Day 0, of all four steroids up to a dosage of 25 mU LH/day. At higher LH dosages, Day 0 ovarian concentrations of androgens and estradiol fell markedly, while progesterone concentrations continued to increase. Histological examination of ovaries revealed increases in the extent of luteinization of granulosa cells in follicles with retained oocytes on both Days 0 and 1 in rats infused with 25 and 50 mU LH/day together with 1 U FSH/day, compared to those observed in rats receiving FSH alone. These findings indicate that the elevated progesterone levels on Day 0 and inhibition of ovulation observed at these LH doses were due to premature luteinization of follicles, thus preventing ovulation. At lower LH doses, no sign (based on histologic or steroidogenic criteria) of premature luteinization was evident, suggesting that the decreased superovulation in these rats was due to decreased follicular maturation and/or increased atresia rather than to luteinization of follicles without ovulation. High androgen:estrogen ratios observed in rats receiving increasing LH infusion rates from 2.5-25 mU/day together with 1 U FSH/day suggest that decreased rate of superovulation in response to FSH treatment together with these LH infusion rates is due in part to follicular atresia associated with elevated ovarian androgen levels resulting from excessive stimulation.