Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
Sci Rep. 2017 Mar 7;7:43459. doi: 10.1038/srep43459.
Oestrogen is an important regulator in reproduction. To understand the role of oestrogen receptor 1 (ESR1) in Leydig cells, we investigated the expression of ESR1 in mouse Leydig cells during postnatal development and the effects of oestrogen on steroidogenesis and proliferation of progenitor Leydig cells (PLCs). In Leydig cells, the ESR1 expression was low at birth, increased until postnatal day 14 at which PLCs were predominant, and then decreased until adulthood. In foetal Leydig cells, ESR1 immunoreactivity increased from birth to postnatal day 14. These suggest that ESR1 is a potential biomarker of Leydig cell development. In PLCs, 17β-estradiol and the ESR1-selective agonist propylpyrazoletriol suppressed human chorionic gonadotropin (hCG)-induced progesterone production and steroidogenic gene expression. The ESR2-selective agonist diarylpropionitrile did not affect steroidogenesis. In PLCs from Esr1 knockout mice, hCG-stimulated steroidogenesis was not suppressed by 17β-estradiol, suggesting that oestrogen inhibits PLC steroidogenesis via ESR1. 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile decreased bromodeoxyuridine uptake in PLCs in the neonatal mice. In cultured PLCs, 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile reduced hCG-stimulated Ki67 and Pcna mRNA expression and the number of KI67-positive PLCs, suggesting that oestrogen inhibits PLC proliferation via both ESR1 and ESR2. In PLCs, ESR1 mediates the oestrogen-induced negative regulation of steroidogenesis and proliferation.
雌激素是生殖的重要调节剂。为了了解雌激素受体 1（ESR1）在睾丸间质细胞中的作用，我们研究了 ESR1 在出生后发育过程中在小鼠睾丸间质细胞中的表达，以及雌激素对祖细胞睾丸间质细胞（PLCs）的类固醇生成和增殖的影响。在睾丸间质细胞中，ESR1 的表达在出生时较低，在 PLCs 占优势的第 14 天增加，然后在成年期下降。在胎儿睾丸间质细胞中，ESR1 免疫反应性从出生到第 14 天增加。这表明 ESR1 是睾丸间质细胞发育的潜在生物标志物。在 PLCs 中，17β-雌二醇和 ESR1 选择性激动剂丙基吡唑三醇抑制人绒毛膜促性腺激素（hCG）诱导的孕酮产生和类固醇生成基因表达。ESR2 选择性激动剂二芳基丙腈对类固醇生成没有影响。在 Esr1 敲除小鼠的 PLCs 中，hCG 刺激的类固醇生成不受 17β-雌二醇的抑制，这表明雌激素通过 ESR1 抑制 PLC 的类固醇生成。17β-雌二醇、丙基吡唑三醇和二芳基丙腈降低了新生小鼠 PLCs 中的溴脱氧尿苷摄取。在培养的 PLCs 中，17β-雌二醇、丙基吡唑三醇和二芳基丙腈降低了 hCG 刺激的 Ki67 和 Pcna mRNA 表达以及 Ki67 阳性 PLCs 的数量，这表明雌激素通过 ESR1 和 ESR2 抑制 PLC 增殖。在 PLCs 中，ESR1 介导雌激素诱导的类固醇生成和增殖的负调节。
