Progesterone receptors: various forms and functions in reproductive tissues

Abstract

The unequivocal role of progesterone in a variety of events like ovulation, mammary gland development, establishment and maintenance of pregnancy etc are well established. Also the data are accumulating on its role in male reproductive events. In vertebrates and humans, the biological activity of progesterone is mediated by two progesterone receptor proteins PR-A and PR-B, that arise from the same gene and are the members of nuclear receptor superfamily of transcriptional factors. Several studies have demonstrated that the blockage of progesterone receptor using antiprogestins impairs folliculogenesis, ovulation, implantation and pregnancy. Progesterone receptor (PR), have also been detected in human spermatozoa. However, unlike the conventional PR, sperm PR was localized on the membrane and showed distinct characteristics in terms of its size. There are data to demonstrate the inhibition of progesterone driven functions such as hyperactive motility, acrosome reaction on neutralization of sperm membrane PR with specific antibodies against PR. Further significant decrease in the % of PR positive spermatozoa was observed in infertile cases as compared to the fertile men. This indicated that PR can serve as the marker to define the fertilizing potential of the spermatozoa. Recently we have also shown that the PR is expressed in human testis. This reinforced that this PR protein is an inherent testicular protein and not a secretion of accessory reproductive organs. This review compiles the major observations on the forms of the progesterone receptor in various reproductive tissues.

Molecular toxicology of polybrominated diphenyl ethers: nuclear hormone receptor mediated pathways

“…46 4 Androgen receptor and progesterone receptor pathways Both androgen receptor (AR) and progesterone receptor (PR) are type I receptors. 47,48 AR is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone (DHT), and regulates the genes critical for the development and maintenance of the male sexual phenotype. 47 Similarly, PR is activated by the steroid hormone progesterone, which plays a central role in diverse reproductive events associated with the establishment and maintenance of pregnancy and alveolar development in the breast and sexual behavior.…”

“…47 Similarly, PR is activated by the steroid hormone progesterone, which plays a central role in diverse reproductive events associated with the establishment and maintenance of pregnancy and alveolar development in the breast and sexual behavior. 48 Multiple studies in animal experiments raised concerns that exposure to PBDEs may affect AR and PR signaling pathways. For instance, Stoker et al found that DE-71 delayed puberty and suppressed the growth of androgen-dependent tissues in male rat following a peri-pubertal exposure, demonstrating the in vivo antiandrogenic properties of PBDEs.…”

Nuclear Receptors and Their Selective Pharmacologic Modulators

“…The PR (NR3C2) is encoded by a single gene on chromosome 11q22 that uses two separate promoters and start sites to generate PR-A and PR-B isoforms (Conneely et al, 1987b;Law et al, 1987;Misrahi et al, 1987;Gadkar-Sable et al, 2005). The PR-A isoform is 769 amino acids, whereas the PR-B isoform is 933 amino acids, with the additional 165 amino acids in PR-B located in the N terminus (Kastner et al, 1990).…”

T-SP1: a novel serine protease-like protein predominantly expressed in testis

“…The latter assumption seems to be underlined by the fact that the MatInspector software (www.genomatix.de) calculates putative binding sites for the progesterone receptor and the androgen receptor 719 bp (TAagtcaTGTTCT) and 1642 bp (GGttCActcTCTTCT) upstream of the transcription initiation site of T-SP1. Thus, T-SP1 expression may be regulated by progesterone and androgens which bind to these receptors (Holdcraft and Braun, 2004;Gadkar-Sable et al, 2005). A hormone-dependent regulation of kallikreinrelated peptidases has already been demonstrated in breast and prostate cancer Diamandis, 2006, 2008).…”