Membrane progesterone receptors: evidence for neuroprotective, neurosteroid signaling and neuroendocrine functions in neuronal cells.
Membrane progesterone receptors: evidence for neuroprotective, neurosteroid signaling and neuroendocrine functions in neuronal cells.
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DOI：
10.1159/000339822
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发表时间：
2012
影响因子：
4.1
通讯作者：
Pang Y
中科院分区：
文献类型：
--
作者：
Thomas P;Pang Y
膜孕酮受体（membrane programme receptor，mPRs）是一种新的G蛋白偶联受体，属于孕酮和脂肪Q受体家族（PAQR），在生殖系统中介导多种快速的、细胞表面启动的孕酮作用，涉及细胞内信号通路的激活（即非经典作用）。mPR在大脑中高度表达，但对其神经功能的研究仅在单个神经元细胞系GT 1 -7细胞中进行，其具有可忽略的核孕酮受体（PR）表达。GT 1 -7细胞在其质膜上表达mPRα和mPRβ，这与存在高亲和力、特异性[3 H]-孕酮受体结合有关。神经甾体别孕烯醇酮是重组mPRα的有效配体，其相对结合亲和力为孕酮的7.6%。别孕烯醇酮作为一种有效的mPR激动剂作用于GT 1 -7细胞，模拟孕酮诱导的cAMP积累减少及其在低纳摩尔浓度下的抗凋亡作用。cAMP水平的降低与孕酮诱导的灌流GT 1 -7细胞GnRH脉冲式分泌的快速下调有关。最近认为mPR是碱性神经酰胺酶并介导鞘脂信号传导的观点并没有得到以下经验证据的支持：TNFα不与人细胞中过度表达的mPR结合，外源性鞘磷脂酶在通过mPR模拟孕酮作用以诱导鱼类卵母细胞减数分裂成熟方面无效。总之，这些最近的研究表明，mPRs介导的孕酮和allopregnanolone的神经保护作用，也可能是在孕酮诱导的抑制脉冲式GnRH分泌在GT 1 -7细胞的中介。
Membrane progesterone receptors (mPRs) are novel G protein-coupled receptors belonging to the progestin and adipoQ receptor family (PAQR) that mediate a variety of rapid, cell surface-initiated progesterone actions in the reproductive system involving activation of intracellular signaling pathways (i.e. nonclassical actions). The mPRs are highly expressed in the brain but research on their neural functions has only been conducted in a single neuronal cell line, GT1-7 cells, which have negligible nuclear progesterone receptor (PR) expression. GT1-7 cells express mPRα and mPRβ on their plasma membranes which is associated with the presence of high affinity, specific [3H]-progesterone receptor binding. The neurosteroid, allopregnanolone, is an effective ligand for recombinant mPRα with a relative binding affinity of 7.6% that of progesterone. Allopregnanolone acts as a potent mPR agonist on GT1-7 cells, mimicking the progesterone-induced decrease in cAMP accumulation and its antiapoptotic actions at low nanomolar concentrations.. The decrease in cAMP levels is associated with rapid progesterone-induced down-regulation of GnRH pulsatile secretion from perifused GT1-7 cells. The recent suggestion that mPRs are alkaline ceramidases and mediate sphingolipid signaling is not supported by empirical evidence that TNFα does not bind to mPRs over expressed in human cells and that exogenous sphingomyelinase is ineffective in mimicking progestin actions through mPRs to induce meiotic maturation of fish oocytes. Taken together, these recent studies indicate that mPRs mediate neuroprotective effects of progesterone and allopregnanolone and are also the likely intermediaries in progesterone-induced inhibition of pulsatile GnRH secretion in GT1-7 cells.
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影响因子：
3.6
作者：
Buschiazzo, Jorgelina;Alonso, Telma S.;Bonini, Ida C.
通讯作者：
Bonini, Ida C.
影响因子：
3.5
作者：
DEBOLD, JF;FRYE, CA
通讯作者：
FRYE, CA
影响因子：
3
作者：
Charles NJ;Thomas P;Lange CA
通讯作者：
Lange CA
DOI：
10.1073/pnas.220302597
发表时间：
2000-11-07
影响因子：
11.1
作者：
Bayaa, M;Booth, RA;Liu, XJ
通讯作者：
Liu, XJ
影响因子：
4
作者：
Dosiou, C.;Hamilton, A. E.;Giudice, L. C.
通讯作者：
Giudice, L. C.