Progesterone receptors A and B differentially modulate corticotropin-releasing hormone gene expression through a cAMP regulatory element

Abstract

Corticotrophin-releasing hormone (CRH) plays a major role in mechanisms controlling human pregnancy and parturition. Gene regulation by progesterone may be a key point in the control of placental CRH production. Studies in primary placental cells show that antagonism of progesterone activity or production by RU486 or trilostane leads to an increase in CRH promoter activity. This effect can be reversed by the addition of progesterone. Overexpression of progesterone receptor A (PR-A) or glucocorticoid receptor resulted in a decrease in CRH promoter activity following progesterone treatment, whereas an increase in promoter activity was observed with overexpressed PR-B. Studies including mutation of the cAMP regulatory element (CRE) confirm this site to be essential for the progesterone-mediated effects. In summary, our results demonstrate that progesterone regulates CRH gene transcription via a CRE in the CRH promoter and that PR-A and PR-B exhibit different actions in the regulation of CRH gene expression.

Progesterone regulates catechol-O-methyl transferase gene expression in breast cancer cells: Distinct effect of progesterone receptor isoforms

“…While PR-A is associated with progesterone-induced COMT upregulation, PR-B is associated with downregulation of COMT expression. The distinctive effect of PR-B and PR-A on COMT expression is consistent with other observations that PR-A and PR-B have an opposing effect on the expression of many genes [37][38][39][40]. The underpinning mechanism of the distinct activities of PR-A and PR-B in gene expression is not well understood, although it has been shown that distinct coregulator recruitment and usage are involved at some levels [41].…”

The cyclic AMP-dependent protein kinase A pathway is involved in progesterone effects on calcitonin secretion from TT cells

“…For example, progesterone can stimulate JNK activation both through the MEK/p42 MAPK pathway and MEK/p42 MAPK-independent pathways in Xenopus oocytes (Bagowski et al, 2001). Ni and co-workers reported that progesterone regulates CRH gene transcription via a cAMP regulatory element in the CRH promoter (Ni et al, 2004). Recently, the human membrane progesterone receptor (Jang and Yi, 2005) and receptor gene were identified (Bernauer et al, 2001).…”

Difference in Progesterone-Receptor Isoforms Ratio Between Early and Late First-Trimester Human Trophoblast Is Associated with Differential Cell Invasion and Matrix Metalloproteinase 2 Expression

“…Both isoforms share an identical ligand-binding domain, which includes an activation function. The PGRA and PGRB can be considered as two independent receptors that display different transcriptional activities [16,17]. It has been described that a different set of genes is regulated by progesterone in cells that express different PGR isoform profiles [16][17][18][19].…”