PROGESTERONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE PRIMATE CORPUS-LUTEUM DURING THE MENSTRUAL-CYCLE - POSSIBLE REGULATION BY PROGESTERONE

In classical target tissues, progesterone (P) down-regulates its own r eceptor, yet in the primate corpus luteum, progesterone receptors (PRs ) exist within a very high local P milieu. The percentage of luteal ce lls staining PR-positive by immunocytochemistry is highest at the midl uteal phase of the menstrual cycle during the period of peak serum P. To investigate the regulation of luteal PRs, we developed a solution h ybridization/ribonuclease protection assay for the analysis of PR mess enger RNA (mRNA) in macaque corpora lutea (n = 3-4/group). A 332-basep air fragment of the macaque PR complementary DNA corresponding to the hormone-binding region was used as a template for riboprobe production ; the specific hybridization of this riboprobe with PR mRNA was confir med with Northern analysis. P regulation of luteal PR mRNA was investi gated by administering trilostane, a 3 beta-hydroxysteroid dehydrogena se inhibitor, to female rhesus macaques beginning on day 6 or 7 of the luteal phase, which reduced serum P until the time of lutectomy. By 1 8 h after trilostane treatment, luteal PR mRNA levels were significant ly elevated compared to untreated control values (mean +/- SEM, 2.0 +/ - 0.4 us. 0.7 +/- 0.3; P < 0.05). Reduction in P levels for 4 days aft er trilostane administration decreased luteal PR mRNA levels compared with control values (0.50 +/- 0.02 vs. 1.1 +/- 0.2; P < 0.05). To char acterize changes in PR mRNA during the lifespan of the corpus luteum, mRNA levels in luteal tissues from the early, mid-, mid-late, and late luteal phases were determined. PR mRNA levels were lowest during the early luteal phase and increased (P < 0.05) 3-fold by the mid-late lut eal phase; this higher PR mRNA level was maintained throughout the rem ainder of the luteal phase. These data indicate that P or a metabolite may acutely regulate primate luteal PR mRNA in a manner consistent wi th PR regulation in classical P target tissues. In contrast, PR mRNA l evels parallel increases in P and PR-positive luteal cells during the early, mid-, and mid-late portions of the luteal phase. High PR mRNA l evels are maintained during luteal regression as P and the percentage of PR-positive cells decline, suggesting that PR and PR mRNA are regul ated in an asynchronous manner during the lifespan of the corpus luteu m in the menstrual cycle.