To elucidate the mechanisms by which prostaglandin F2 alpha (PGF2 alpha) permanently inhibits LH-dependent steroidogenesis during luteolysis, we investigated the effect on luteal LH receptor mRNA levels of the stable PGF2 alpha analogue cloprostenol injected into adult pseudopregnant rats on different days during the luteal period. After treatment, LH receptor mRNA expression was determined by RNase protection assay. Twelve hours after cloprostenol injection on Day 8 of pseudopregnancy, the luteal LH receptor mRNA levels were drastically reduced (0.95 +/- 0.18 fmol mRNA/microgram DNA, p < 0.01) as compared with those in untreated controls (12.3 +/- 1.3 fmol mRNA/microgram DNA) or in corresponding controls given an injection of saline (8.8 +/- 0.7 fmol mRNA/microgram DNA) (n = 6-8 per group). At 24 h the levels rose to 4.3 +/- 0.8 fmol mRNA/ microgram DNA but were still significantly decreased compared to control values. Forty-eight hours after cloprostenol injection, the luteal LH receptor mRNA levels were not significantly different from control levels; but if the rats received an injection every twelfth hour, levels were significantly decreased compared to those in controls. When PGF2 alpha was injected, LH receptor mRNA levels were reduced in the same manner as seen after cloprostenol injection. LH receptor mRNA of young corpora lutea (CL) (Day 3) was more resistant to down-regulation by cloprostenol than that of CL of the mid (Day 8)-or late (Day 11) luteal phase. On the eighth day of pseudopregnancy, serum progesterone levels were decreased at 0.5 h after cloprostenol injection and fell further at 3 h; serum 20 alpha-dihydroprogesterone levels were first increased at 7 h after cloprostenol injection. We conclude that luteal LH receptor mRNA expression is under direct regulatory control by PGF2 alpha in a both time-and dose-dependent manner and thereby may decisively contribute to the inhibition of LH responsiveness during luteolysis.
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