The Ratio of Progesterone Receptor Isoforms Changes in the Monkey Corpus Luteum During the Luteal Phase of the Menstrual Cycle1

Abstract

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 progesterone receptors (PRs), and PRs are detectable by immunocytochemistry in the monkey corpus luteum. However, changes in total luteal PR and PR isoform expression have not been quantitated in the corpus luteum during its life span in the menstrual cycle. This study was initiated to identify and quantify PR isoforms in the macaque corpus luteum throughout the luteal phase of the natural cycle by means of Western blotting. Several antibodies generated against the human PR recognized two bands of consistent molecular weights in monkey tissues, and these bands comigrated with PR-A and PR-B from human T47D cells. Taken together, these 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 approximately 90,000 and 120,000, respectively. PRs were detected in a variety 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 decidua, 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 antiprogestins in vitro, the temporal changes in PR-B:PR-A in the monkey corpus luteum may contribute to functional differences in luteal responses to progesterone and other steroids in vivo.

The Effects of Luteinizing Hormone Ablation/Replacement Versus Steroid Ablation/Replacement on Gene Expression in the Primate Corpus Luteum

“…ADAMTS-1, a disintegrin and metalloproteinase with thrombospondin repeats-1 ]. This differential response could also be related to changes in the ratio of PR A:B isoforms as the luteal lifespan progresses (Duffy et al, 1997). The current analysis also detected appreciable mRNA levels for the novel membrane progestin receptor PGRMC1 in macaque luteal tissue.…”

Induction of G protein-coupled estrogen receptor (GPER) and nuclear steroid hormone receptors by gonadotropins in human granulosa cells

“…However, there is some confusion about the relative amounts of each isoform in the corpus luteum in different species. In the primate corpus luteum, Western blotting suggested that PR-B is the major isoform (Duffy et al 1997). In contrast, in human corpora lutea PR-A was confirmed to be higher using Western blotting (Misao et al 1998).…”

Expression of Estrogen and Progesterone Receptors in the Bovine Ovary During Estrous Cycle and Pregnancy

“…Both isoforms of PR are expressed in a number of vertebrate species, including rodents (14) and humans (15), and the ratios of the individual isoforms vary in reproductive tissue as a consequence of developmental (14) and hormonal status (16). Although the physiological significance of these variations is unknown, the conservation of these two receptor isoforms and the elaborate genomic mechanisms for their generation suggest that their differential expression may be crucial for the appropriate cellular responses to P (17).…”