Functions of Membrane Progesterone Receptors (mPRs, PAQRs) in Nonreproductive Tissues

THOMAS, PETER; PANG, YEFEI; CAMILLETTI, MARIA ANDREA; CASTELNOVO, LUCA

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2022

0013-7227

45 Abstract46 Gender differences in a wide variety of physiological parameters have implicated the ovarian47 hormones, estrogens and progesterone, in the regulation of numerous nonreproductive tissue48 functions. Rapid, nongenomic (nonclassical) progesterone actions mediated by membrane49 progesterone receptors (mPRs), which belong to the progestin and AdipoQ receptor (PAQR)50 family, have been extensively investigated in reproductive and nonreproductive tissues since51 their discovery in fish ovaries 20 years ago. The five mPR subtypes (α,β,γ,δ,ε) are widely52 distributed in vertebrate tissues and are often expressed in the same cells as the nuclear53 progesterone receptor (PR) and progesterone receptor membrane component one (PGRMC1),54 thereby complicating investigations of mPR-specific functions. Nevertheless, mPR-mediated55 progesterone actions have been identified in a wide range of reproductive and nonreproductive56 tissues and distinguished from nuclear PR-mediated ones by knockdown of these receptors with57 siRNA in combination with a pharmacological approach using mPR- and PR-specific agonists.58 There are several recent reviews on the roles of the mPRs in vertebrate reproduction and cancer,59 whereas there have been no comprehensive assessments of mPR functions in nonreproductive60 tissues. Therefore, this paper briefly reviews mPR functions in a broad range of nonreproductive61 tissues. The evidence that mPRs mediate progesterone and progestogen effects on62 neuroprotection, lordosis behavior, respiratory control of apnea, olfactory responses to63 pheromones, peripheral nerve regeneration, regulation of prolactin secretion in prolactinoma,64 immune functions, and protective functions in vascular endothelial and smooth muscle cells is365 critically reviewed. The ubiquitous expression of mPRs in vertebrate tissues suggests mPRs66 regulate many additional nonreproductive functions that remain to be identified.