{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:40:12Z","timestamp":1791398412850,"version":"4.3.3"},"reference-count":48,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,1]]},"abstract":"<jats:p>Three members of the progestin and adipoQ receptor (PAQR) family, PAQR-7, PAQR-8, and PAQR-5 [membrane progesterone (P4) receptor (PR) (mPR)\u03b1, mPR\u03b2, and mPR\u03b3], function as plasma mPRs coupled to G proteins in mammalian cells, but the characteristics of two other members, PAQR6 and PAQR9 (mPR\u03b4 and mPR\u03f5), remain unclear, because they have only been investigated in yeast expression systems. Here, we show that recombinant human mPR\u03b4 and mPR\u03f5 expressed in MDA-MB-231 breast cancer cells display specific, saturable, high-affinity [3H]-P4 binding on the plasma membranes of transfected cells with equilibrium dissociation constants (Kds) of 2.71 and 2.85 nm, respectively, and low affinity for R5020, characteristics typical of mPRs. P4 treatment increased cAMP production as well as [35S]-guanosine 5\u2032-triphosphate (GTP)\u03b3S binding to transfected cell membranes, which was immunoprecipitated with a stimulatory G protein antibody, suggesting both mPR\u03b4 and mPR\u03f5 activate a stimulatory G protein (Gs), unlike other mPRs, which activate an inhibitory G protein (Gi). All five mPR mRNAs were detected in different regions of the human brain, but mPR\u03b4 showed greatest expression in many regions, including the forebrain, hypothalamus, amygdala, corpus callosum, and spinal cord, whereas mPR\u03f5 was abundant in the pituitary gland and hypothalamus. Allopregnanolone and other neurosteroids bound to mPR\u03b4 and other mPRs and acted as agonists, activating second messengers and decreased starvation-induced cell death and apoptosis in mPR\u03b4-transfected cells and in hippocampal neuronal cells at low nanomolar concentrations. The results suggest that mPR\u03b4 and mPR\u03f5 function as mPRs coupled to G proteins and are potential intermediaries of nonclassical antiapoptotic actions of neurosteroids in the central nervous system.<\/jats:p>","DOI":"10.1210\/en.2012-1772","type":"journal-article","created":{"date-parts":[[2012,11,16]],"date-time":"2012-11-16T23:45:00Z","timestamp":1353109500000},"page":"283-295","source":"Crossref","is-referenced-by-count":210,"title":["Characterization, Neurosteroid Binding and Brain Distribution of Human Membrane Progesterone Receptors \u03b4 and \u03f5 (mPR\u03b4 and mPR\u03f5) and mPR\u03b4 Involvement in Neurosteroid Inhibition of Apoptosis"],"prefix":"10.1210","volume":"154","author":[{"given":"Yefei","family":"Pang","sequence":"first","affiliation":[{"name":"Marine Science Institute, University of Texas at Austin, Port Aransas, Texas 78373"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Dong","sequence":"additional","affiliation":[{"name":"Marine Science Institute, University of Texas at Austin, Port Aransas, Texas 78373"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thomas","sequence":"additional","affiliation":[{"name":"Marine Science Institute, University of Texas at Austin, Port Aransas, Texas 78373"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613410729600_B1","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1073\/pnas.0436133100","article-title":"Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor.","volume":"100","author":"Zhu","year":"2003","journal-title":"Proc Natl Acad Sci 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