The steroid hormone oroaesterone exerts pleiotrophic functions in many cell types and has a key role In many aspects of female reproduction. It is well established that progesterone controls transcriptional activation through binding to nuclear progesterone receptors. However. progesterone also initiates rapid non-genomic signalling events. but the underlying mechanisms are poorly understood. Recently. a group of potential membrane progesterone receptors (mPRc.c B. y) was isolated from the spotted seatrout and subseguently identified in many other species. The mPRs belong to the larger. highly conserved family of progestin and adiponectin receptors (PAQR) and have structural similarity to seven transmembranespanning G protein-coupled receptors. To further define the role of these mPRs in human reproductive tissues expression profiling was performed. A comparison of the expression of mPR transcriots with that of two related PAQR family members. PAQRIII and PAQRIX. in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. However. functional analyses demonstrated that neither human or fish mPRs mediate cAMP production. Mitogen-activated protein kinase activation or�· calcium mobilization in response to progesterone. Furthermore. human mPRa localizes to the endoplasmic reticulum and not the plasma membrane. Other putative progesterone binding moieties. inclUding progesterone receptor membrane component 1 and 2 (PGRMC-1/-2). were also investigated. Like PAQR family members, PGRMC-1 and -2 are expressed in a reoulated manner in pregnant and non-pregnant uterine tissues but evidence of their roles in prooesterone responses remains elusive. Thus. these results do not support a role for the mPRs in non-genomic proaesterone signal transduction in human uterine tissues.
