Differential Responses of Progesterone Receptor Membrane Component-1 (Pgrmc1) and the Classical Progesterone Receptor (Pgr) to 17β-Estradiol and Progesterone in Hippocampal Subregions that Support Synaptic Remodeling and Neurogenesis
Differential Responses of Progesterone Receptor Membrane Component-1 (Pgrmc1) and the Classical Progesterone Receptor (Pgr) to 17β-Estradiol and Progesterone in Hippocampal Subregions that Support Synaptic Remodeling and Neurogenesis
复制标题
DOI：
10.1210/en.2011-1699
复制
发表时间：
2012-02-01
期刊：
影响因子：
4.8
通讯作者：
Finch, Caleb E.
中科院分区：
文献类型：
--
作者：
Bali, Namrata;Arimoto, Jason M.;Finch, Caleb E.
孕激素（P4）和雌二醇（E2）调节神经发生和突触重塑在大鼠动情周期和传入神经损伤的反应，但很少有人知道与这些过程相关的海马孕酮受体的类固醇调节。我们研究了孕激素受体膜成分-1（Pgrmc 1）和经典孕激素受体（Pgr）的神经元表达，通过原位杂交和免疫组织化学。Pgr是一种转录因子，与突触重塑和P4的其他主要作用有关，而Pgrmc 1与P4依赖的成体神经祖细胞增殖和P4对膜的快速作用有关。卵巢切除的成年大鼠给予E2，P4，或E2+P4两个时间表：4天模型的啮齿动物发情周期和30天模型的绝经后激素治疗。Pgr仅在CA 1区锥体神经元呈神经反应性，P4仅在30 d时部分拮抗E2对Pgr的诱导作用。在CA 3锥体和齿状回（DG）神经元，PGR在很大程度上是无反应的所有激素治疗。与Pgr相反，Pgrmc 1通常由E2和/或P4在整个海马CA 1，CA 3和DG神经元中诱导。在DG的神经祖细胞（溴脱氧尿苷和doublecortin免疫阳性）中，检测到Pgrmc 1和Pgr。E2和P4对海马Pgrmc 1和Pgr的差异调节可能指导激素治疗中支持神经发生和突触再生的药物开发。（内分泌学153：759-769，2012）
Progesterone (P4) and estradiol (E2) modulate neurogenesis and synaptic remodeling in the hippocampus during the rat estrous cycle and in response to deafferenting lesions, but little is known about the steroidal regulation of hippocampal progesterone receptors associated with these processes. We examined the neuronal expression of progesterone receptor membrane component-1 (Pgrmc1) and the classical progesterone receptor (Pgr), by in situ hybridization and immunohistochemistry. Pgr, a transcription factor, has been associated with synaptic remodeling and other major actions of P4, whereas Pgrmc1 is implicated in P4-dependent proliferation of adult neuro-progenitor cells and with rapid P4 effects on membranes. Ovariectomized adult rats were given E2, P4, or E2+P4 on two schedules: a 4-d model of the rodent estrous cycle and a 30-d model of postmenopausal hormone therapy. Pgr was hormonally responsive only in CA1 pyramidal neurons, and the induction of Pgr by E2 was partly antagonized by P4 only on the 30-d schedule. In CA3 pyramidal and dentate gyrus (DG) neurons, Pgr was largely unresponsive to all hormone treatments. In contrast to Pgr, Pgrmc1 was generally induced by E2 and/or P4 throughout the hippocampus in CA1, CA3, and DG neurons. In neuroprogenitor cells of the DG (immunopositive for bromodeoxyuridine and doublecortin), both Pgrmc1 and Pgr were detected. The differential regulation of hippocampal Pgrmc1 and Pgr by E2 and P4 may guide drug development in hormonal therapy for support of neurogenesis and synaptic regeneration. (Endocrinology 153: 759-769, 2012)