Department of Basic Medical Sciences, University of Arizona College of Medicine, 425 North 5th Street, Phoenix, Arizona 85004, USA.
Endocrinology. 2012 Sep;153(9):4432-43. doi: 10.1210/en.2012-1469. Epub 2012 Jul 9.
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.
虽然有几项研究报道了膜孕激素（P(4)）受体（mPR）在各种组织中的定位，但很少有研究试图描述这些受体在大脑中的分布和调节。在本研究中，我们研究了两种 mPR 亚型，mPRα和 mPRβ，在已知表达雌二醇（E(2)）依赖性（视前区（POA）和下丘脑）和独立（皮质）经典孕激素受体的大脑区域中的表达。用从大鼠皮质、下丘脑和 POA 制备的质膜进行的饱和结合和 Scatchard 分析表明，存在高亲和力、特异性 P(4)结合位点，这是 mPR 的特征。使用定量 RT-PCR，我们发现 mPRβ mRNA 的表达水平高于 mPRα，这表明 mPRβ可能是大鼠大脑中的主要 mPR 亚型。我们还使用免疫组织化学方法绘制了 mPRβ 蛋白的分布图谱。mPRβ-免疫反应性神经元在下丘脑的某些核（室旁核、腹内侧下丘脑和弓状核）、前脑（内侧隔核和水平对角带）和中脑（动眼神经核和红核）以及皮质和丘脑的许多区域高度表达。用苯甲酸雌二醇处理去卵巢雌性大鼠增加了内侧隔核内的 mPRβ 免疫反应性，但不增加内侧 POA、水平对角带或动眼神经核内的 mPRβ 免疫反应性。总之，这些发现表明 mPRβ 在啮齿动物大脑中的广泛分布可能有助于影响行为、内分泌、运动和感觉系统的功能。此外，E(2)对 mPRβ 的调节表明了一种机制，通过这种机制，雌激素可以调节特定脑区内的 P(4)功能，从而可能影响行为。
