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睾丸细胞中的雌激素信号转导。

Estrogen signaling in testicular cells.

机构信息

Université de Caen Basse-Normandie, Esplanade de la Paix, Caen, France.

出版信息

Life Sci. 2011 Oct 10;89(15-16):584-7. doi: 10.1016/j.lfs.2011.06.004. Epub 2011 Jun 15.

DOI:10.1016/j.lfs.2011.06.004
PMID:21703280
Abstract

Aromatase transforms irreversibly androgens into estrogens and is present in the endoplasmic reticulum of various tissues including the mammalian testis. In rat all testicular cells except peritubular cells express aromatase. Indeed in adult rat germ cells (pachytene spermatocytes and round spermatids) we have demonstrated the presence of a functional aromatase (transcript, protein and biological activity) and the estrogen output is equivalent to that of Leydig cells. In addition in the adult rat, transcripts of aromatase vary according to the germ cell type and to the stages of seminiferous epithelium. By contrast with the androgen receptors mainly localized in somatic cells, estrogen receptors (ERs) are described in most of the testicular cells including germ cells. Moreover, besides the presence of high affinity ERα and/or ERβ, a rapid membrane effect has been recently reported and we demonstrated that GPR30 (a transmembrane intracellular estrogen receptor) is expressed in adult rat pachytene spermatocytes. Therefore estrogens through both GPR30 and ERα are able to activate the rapid EGFR/ERK/c-jun signaling cascade, which in turn triggers an apoptotic mitochondrial pathway involving an increase in Bax expression and a concomitant reduction of cyclin A1 and B1 gene levels. In another study in round spermatids of adult rat we have shown that the rapid membrane effect of estradiol is also efficient in controlling apoptosis and maturation / differentiation of these haploid germ cells. In man the presence of a biologically active aromatase and of estrogen receptors has been reported in Leydig cells, but also in immature germ cells and ejaculated spermatozoa. Thus the role of estrogen (intracrine, autocrine and / or paracrine) in spermatogenesis (proliferation, apoptosis, survival and maturation) and more generally, in male reproduction is now evidenced taking into account the simultaneous presence of a biologically active aromatase and the widespread distribution of estrogen receptors especially in haploid germ cells.

摘要

芳香酶不可逆地将雄激素转化为雌激素,并存在于包括哺乳动物睾丸在内的各种组织的内质网中。在大鼠中,除了支持细胞外,所有睾丸细胞都表达芳香酶。事实上,在成年大鼠生殖细胞(粗线期精母细胞和圆形精子细胞)中,我们已经证明存在功能性芳香酶(转录本、蛋白质和生物学活性),并且雌激素的产生量与间质细胞相当。此外,在成年大鼠中,芳香酶的转录本根据生精上皮的生殖细胞类型和阶段而变化。与主要定位于体细胞的雄激素受体不同,雌激素受体(ERs)存在于大多数睾丸细胞中,包括生殖细胞。此外,除了存在高亲和力的 ERα 和/或 ERβ 外,最近还报道了一种快速的膜效应,我们证明 GPR30(一种跨膜细胞内雌激素受体)在成年大鼠粗线期精母细胞中表达。因此,雌激素通过 GPR30 和 ERα 都能够激活快速的 EGFR/ERK/c-jun 信号级联,从而触发涉及 Bax 表达增加和细胞周期蛋白 A1 和 B1 基因水平降低的凋亡线粒体途径。在另一项针对成年大鼠圆形精子细胞的研究中,我们表明雌二醇的快速膜效应也能有效地控制这些单倍体生殖细胞的凋亡和成熟/分化。在人类中,已经报道了活性芳香酶和雌激素受体存在于间质细胞中,但也存在于未成熟的生殖细胞和射出的精子中。因此,雌激素(胞内、自分泌和/或旁分泌)在精子发生(增殖、凋亡、存活和成熟)以及更普遍的男性生殖中的作用现在已经得到证实,考虑到同时存在有生物活性的芳香酶和广泛分布的雌激素受体,特别是在单倍体生殖细胞中。

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