REGULATION OF ANTERIOR-PITUITARY GONADOTROPIN SUBUNIT MESSENGER-RNA LEVELS DURING THE PREOVULATORY GONADOTROPIN SURGE - A PHYSIOLOGICAL-ROLE OF PROGESTERONE IN REGULATING LH-BETA AND FSH-BETA MESSENGER-RNA LEVELS

In a previous study we demonstrated that in the ovariectomized estroge n-primed immature rat, progesterone induced a gonadotropin surge while the gonadotropin mRNA subunit levels were either suppressed or unalte red. This observation has now been confirmed using more frequent time points. Progesterone administered at 0900 h was found to suppress LH-b eta mRNA levels at 1300, 1400, and 0800 h the next day, with no subseq uent effects at 1000, 1200 or 1600 h. FSH-beta mRNA levels were unaffe cted by progesterone except for a slight elevation at 1400 h and a sup pression at 0800 h. Progesterone was either suppressive or had no effe ct on alpha mRNA levels. Since elevations in LH-beta and FSH-beta mRNA levels were observed in the cycling rat, the observed differences in the ovariectomized estrogen-primed rat could be due to a higher basal synthesis occurring due to ovariectomy. This was indeed the case becau se LH-beta and FSH-beta mRNA levels were 3.7- and 42.7-fold higher in such animals as compared to intact estrogen-primed rats. In contrast t o the ovariectomized estrogen-primed rats, in intact estrogen-primed r ats LH-beta mRNA levels were increased at 1000 h and FSH-beta mRNA lev els were increased at 1000, 1200 and 1300 h after the administration o f progesterone. In pregnant mare's serum gonadotropin-primed immature rats, LH-beta. FSH-beta and alpha-subunit mRNA levels were significant ly elevated at 1800 and 2000 h, paralleling the serum LH and FSH surge . The progesterone antagonist RU486 (0.2 and 1.0 mg) significantly red uced serum LH and FSH levels at 2000 h. The lower dose reduced LH-beta and alpha-subunit mRNA levels at 2000 h and FSH-beta mRNA levels at 1 800 h. The higher dose caused an increase in LH-beta mRNA levels at 12 00 and 1800 h and a decrease in FSH-beta mRNA levels at 1800 and 2000 h. In conclusion, the present study provides evidence that preovulator y progesterone plays an important role in the increase in FSH-beta mRN A levels as well as the release of LH and FSH during the normal preovu latory gonadotropin surge. This relationship appears to be dependent o n the ongoing rate of synthesis because this does not occur in the ova riectomized estrogen-primed rat in which synthesis is at a high basal level. Furthermore, the correlation with FSH appears to be tighter as compared to LH.