RAPID MODULATION OF OVARIAN 3-BETA-HYDROXYSTEROID DEHYDROGENASE DELTA(5)-DELTA(4) ISOMERASE GENE-EXPRESSION BY PROLACTIN AND HUMAN CHORIONIC-GONADOTROPIN IN THE HYPOPHYSECTOMIZED RAT/

In order to better understand the role of prolactin (PRL) and luteiniz ing hormone (LH) on progesterone biosynthesis in the ovary, we have in vestigated the time course (1-9 days) of the effect of PRL and human c horionic gonadotropin (hCG) on ovarian 3 beta-hydroxysteroid dehydroge nase/Delta(5)-Delta(4) isomerase (3 beta-HSD) expression in the hypoph ysectomized rat. As evaluated by quantitative in situ hybridization us ing a S-35 labelled type I 3 beta-HSD cDNA probe, the administration o f hCG for 2, 3 and 9 days induced increases of 63%, 145% and 146% abov e control, respectively, in 3 beta-HSD mRNA levels in ovarian intersti tial cells. The absence of apparent effect of the gonadotropin in othe r ovarian cell types could explain the small modulation of ovarian 3 b eta-HSD protein content and enzymatic activity observed in total ovari an tissue. On the other hand, treatment with PRL caused a rapid decrea se in 3 beta-HSD mRNA levels in corpus luteum by 23%, 63%, 76% and 78% (P < 0.01) following 1, 2, 5 and 9 days of treatment, respectively. T he short-term inhibitory effect of PRL was also observed on ovarian im munoreactive 3 beta-HSD protein, as measured by Western blot analysis, and on 3 beta-HSD activity measured by the conversion of [C-14]dehydr oepiandrosterone into [C-14]androstenedione. The inhibitory effect of PRL on 3 beta-HSD expression and activity is correlated with a progres sive decrease in serum progesterone concentration from a pretreatment value of 4.8 nM to levels below the limit of detection (< 0.13 nM) aft er 7-9 days of treatment with PRL, while serum pregnenolone levels wer e decreased by only approximately 55% after 9 days. The present findin gs indicate that the inhibition of 3 beta-HSD gene expression and acti vity in corpora lutea occurrs early in the luteolytic process induced by PRL and could well play an important role in this process.