Distribution and Estrogen Regulation of Membrane Progesterone Receptor-β in the Female Rat Brain

Abstract

Although several studies have reported the localization of membrane progesterone (P(4)) receptors (mPR) in various tissues, few have attempted to describe the distribution and regulation of these receptors in the brain. In the present study, we investigated expression of two mPR subtypes, mPRα and mPRβ, within regions of the brain, known to express estradiol (E(2))-dependent [preoptic area (POA) and hypothalamus] and independent (cortex) classical progestin receptors. Saturation binding and Scatchard analyses on plasma membranes prepared from rat cortex, hypothalamus, and POA demonstrated high-affinity, specific P(4)-binding sites characteristic of mPR. Using quantitative RT-PCR, we found that mPRβ mRNA was expressed at higher levels than mPRα, indicating that mPRβ may be the primary mPR subtype in the rat brain. We also mapped the distribution of mPRβ protein using immunohistochemistry. The mPRβ-immunoreactive neurons were highly expressed in select nuclei of the hypothalamus (paraventricular nucleus, ventromedial hypothalamus, and arcuate nucleus), forebrain (medial septum and horizontal diagonal band), and midbrain (oculomotor and red nuclei) and throughout many areas of the cortex and thalamus. Treatment of ovariectomized female rats with E(2) benzoate increased mPRβ immunoreactivity within the medial septum but not the medial POA, horizontal diagonal band, or oculomotor nucleus. Together, these findings demonstrate a wide distribution of mPRβ in the rodent brain that may contribute to functions affecting behavioral, endocrine, motor, and sensory systems. Furthermore, E(2) regulation of mPRβ indicates a mechanism through which estrogens can regulate P(4) function within discrete brain regions to potentially impact behavior.

Expression and hormonal regulation of membrane progesterone receptors in human astrocytoma cells

“…By RT-qPCR we Above results agree with other reports in which mPRβ is the predominant mPR in different human and rodent brain regions such as cerebral cortex, cerebellum, pituitary, thalamus, hypothalamus and caudate nucleus [22,43]. In contrast, mPRα is predominantly expressed in human reproductive tissues, though some recent studies have reported its expression in cerebral cortex, hippocampus, thalamus, hypothalamus and cerebellum of rat and mouse [41,44,45].…”

“…In fact, ERE and PRE have been reported in promoter regions of mPRα, mPRβ and mPRγ of catfish [47]. [43]. Similarly, using quantitative PCR, Inteklofer and Petersen reported an upregulation of mPRβ, but no mPRα mRNA in the anteroventral periventricular nucleus (AVPV), ventromedial nucleus and sexually dimorphic nucleus of the preoptic area after implanted E-containing capsules for a longer than 56-h exposure in female rats, while in the same model, P repressed mPRβ gene expression only in AVPV [48].…”

Neuroprotective Effect of Progesterone in MPTP-Treated Male Mice

“…In addition, PROG also binds to membrane PROG receptor (mPR)-α and -β [30]. PR-A, PR-B, and mPR-α are expressed in the striatum [31,32], while PR-A, PR-B, and mPR-β have been found in the substantia nigra [33,34,35]. Whereas the mechanisms of PROG action in the striatum have received little attention, PROG is reported to mediate its effect through multiple mechanisms.…”

Membrane progesterone receptors in reproduction and cancer

“…mPRα is also induced by gonadotropins during seatrout oocyte maturation followed by a dramatic decrease in ovulated oocytes (Zhu et al, 2003b). By contrast, mPRβ gene is highly expressed during zebrafish oocyte maturation and the corresponding protein levels were also increased during this process (Hanna and Zhu, 2009 It has been proposed that during fish oocyte maturation mPRα activates a pertussis toxin-sensitive inhibitory G protein (G i ), which in turn inhibits the activity of adenylyl cyclase (AC) to decrease cAMP levels (Thomas, 2012). In contrast to fish models, it has been reported that mPRβ regulates oocytes maturation in pig and Xenopus (Josefsberg Ben-Yehoshua et al, 2007;Qiu et al, 2008), suggesting that oocyte maturation mediated by specific mPRs subtypes is species dependent In fish, PKA activation by cAMP usually results in the inactivation of MAPK signaling and the inhibition of oocyte maturation by downregulating cyclin B levels (black lines).…”