engleski

The selective contribution of PR isoforms to the cellular and molecular actions of progesterone in reproductive tissues

Progesterone (P) plays a central coordinate role in diverse reproductive events associated with establishment and maintenance of pregnancy. The progesterone responsiveness is determined by the extent of expression of specific progesterone receptors which mediate progesterone action via genomic and non-genomic pathways. In human, rodents, and many other species the genomic actions of progesterone are mediated by intracellular receptors, progesterone receptor A (PR-A) and progesterone receptor B (PR-B), which are members of the nuclear receptor superfamily of transcription factors, and are the product of the same gene transcribed under control of two distinct promoters. The receptors PR-A and PR-B are phosphoproteins with transcriptional activity dependent on the state of phosphorilation of the cognate receptors and/or their coregulator proteins. Spatial and temporal expression of the PR-A and PR-B vary in reproductive tissues as a consequence of the developmental and the hormonal status and during carcinogenesis. The non-genomic action of progesterone is characterized by a rapid response to progesterone (latency of minutes rather than hours), which is independent of transcription regulatory functions of PRs and is executed by at least two mechanisms. The first is PRs mediated via activation of the intracellular phosphorylation cascades. The second mechanism is PR-A and PR-B independent and appears to operate through membrane specific receptors for progesterone. Proper functional communication between the genomic and non-genomic progesterone regulated signaling pathways could be of critical importance for the correct biological activity of progesterone during the establishment and the maintenance of pregnancy. By combining gene array approaches to identify PR downstream signaling pathways and by using genetic mouse models to address the consequences of ablation and/or of potential downstream genes, recent studies have begun to elucidate key signaling pathways that mediate the morphogenic effects of these hormones during pregnancy and carcinogenesis. Current knowledge of the progesterone regulated signaling pathways and progesterone downstream targets will be discussed.

progesterone; progesterone receptors

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