THE RATIO OF PROGESTERONE-RECEPTOR ISOFORMS CHANGES IN THE MONKEY CORPUS-LUTEUM DURING THE LUTEAL-PHASE OF THE MENSTRUAL-CYCLE

Recent evidence suggests that progesterone is required for ovulation, luteinization, and the maintenance of luteal structure and function in primates. Progesterone action is mediated by intracellular progestero ne receptors (PRs), and PRs are detectable by immunocytochemistry in t he monkey corpus luteum. However, changes in total luteal PR and PR is oform expression have not been quantitated in the corpus luteum during its life span in the menstrual cycle. This study was initiated to ide ntify and quantify PR isoforms in the macaque corpus luteum throughout the luteal phase of the natural cycle by means of Western blotting. S everal antibodies generated against the human PR recognized two bands of consistent molecular weights in monkey tissues, and these bands com igrated with PR-A and PR-B from human T47D cells. Taken together, thes e data suggest that the two proteins identified were macaque PR-A and PR-B. The estimated molecular weights of monkey PR-A and PR-B were app roximately 90 000 and 120 000, respectively. PRs were detected in a va riety of macaque tissues, including the endometrium, whole ovary, and decidua, but not in spleen, which is PR-negative by other techniques. Whereas PR-A was the predominant isoform observed in endometrium and d ecidua, PR-B predominated in the ovary without a dominant follicle or corpus luteum as well as in the corpus luteum. In luteal tissue, PR-A levels decreased (p < 0.05) over the course of the luteal phase, while PR-B levels were unchanged. Hence the ratio of PR-B to PR-A (PR-B:PR- A) increased (p < 0.05) from early to very late luteal phase. Since PR -B:PR-A can alter gene expression in response to progestins and antipr ogestins in vitro, the temporal changes in PR-B:PR-A in the monkey cor pus luteum may contribute to functional differences in luteal response s to progesterone and other steroids in vivo.