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发现阿朴脂蛋白在卵巢卵泡功能中的可能作用。

Discovery of a possible role of asprosin in ovarian follicular function.

作者信息

Maylem Excel Rio S, Spicer Leon J, Batalha Isadora, Schutz Luis F

机构信息

Department of Animal and Food Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.

Department of Agriculture, Veterinary, and Rangeland Sciences, University of Nevada, Reno, Nevada, USA.

出版信息

J Mol Endocrinol. 2021 Jan;66(1):35-44. doi: 10.1530/JME-20-0218.

DOI:10.1530/JME-20-0218
PMID:33112803
Abstract

Asprosin is a novel fasting-induced protein encoded by fibrillin-1 (FBN1) gene, produced when FBN1 is cleaved by the enzyme furin, and is associated with insulin resistance and polycystic ovarian syndrome in humans. To characterize mRNA abundance of FBN1, FURIN, and the presumed asprosin receptor, olfactory receptor family 4 subfamily M member 1 (OR4M1) in granulosa (GC) and theca cells (TC), and identify hormones regulating FBN1 mRNA expression, GC and TC from small (1-5 mm; SM) and large (>8 mm; LG) follicles were collected from ovaries of heifers obtained at an abattoir and used for real-time PCR gene expression analysis or in vitro evaluation of hormone regulation and asprosin effects. SMTC had 151-fold greater (P < 0.05) FBN1 mRNA abundance than SMGC, and LGTC had 50-fold greater FBN1 mRNA than LGGC. In contrast, OR4M1 mRNA was 81-fold greater in SMGC than LGGC and did not differ from SMTC, but LGTC had 9-fold greater OR4M1 mRNA than LGGC. FURIN mRNA was 2.6-fold greater in SMTC than SMGC, but did not differ among follicular sizes. In cultured TC, leptin, insulin, LH, IGF1 and steroids did not affect FBN1 mRNA, but TGFB1 increased (P < 0.05) FBN1 mRNA by 2.2-fold; EGF and FGFs increased FBN1 mRNA by 1.3- to 1.5-fold. Asprosin enhanced LH-induced TC androstenedione production, reduced IGF1-induced TC proliferation, and had no effect on progesterone production. Developmental regulation of FBN1, FURIN and OR4M1 along with direct effects of asprosin on TC suggests that asprosin may be a novel regulator of ovarian follicular function.

摘要

阿扑脂蛋白是一种由原纤蛋白-1(FBN1)基因编码的新型禁食诱导蛋白,当FBN1被弗林蛋白酶切割时产生,与人类的胰岛素抵抗和多囊卵巢综合征有关。为了表征颗粒细胞(GC)和卵泡膜细胞(TC)中FBN1、弗林蛋白酶以及假定的阿扑脂蛋白受体嗅觉受体家族4亚家族M成员1(OR4M1)的mRNA丰度,并确定调节FBN1 mRNA表达的激素,从屠宰场获取的小母牛卵巢中收集小(1-5毫米;SM)卵泡和大(>8毫米;LG)卵泡的GC和TC,用于实时PCR基因表达分析或激素调节和阿扑脂蛋白作用的体外评估。SMTC的FBN1 mRNA丰度比SMGC高151倍(P<0.05),LGTC的FBN1 mRNA比LGGC高50倍。相比之下,OR4M1 mRNA在SMGC中比LGGC高81倍,与SMTC无差异,但LGTC的OR4M1 mRNA比LGGC高9倍。FURIN mRNA在SMTC中比SMGC高2.6倍,但在不同卵泡大小之间无差异。在培养的TC中,瘦素、胰岛素、促黄体生成素(LH)、胰岛素样生长因子1(IGF1)和类固醇不影响FBN1 mRNA,但转化生长因子β1(TGFB1)使FBN1 mRNA增加(P<0.05)2.2倍;表皮生长因子(EGF)和成纤维细胞生长因子(FGFs)使FBN1 mRNA增加1.3至1.5倍。阿扑脂蛋白增强LH诱导的TC雄烯二酮生成,降低IGF1诱导的TC增殖,对孕酮生成无影响。FBN1、弗林蛋白酶和OR4M1的发育调节以及阿扑脂蛋白对TC的直接作用表明,阿扑脂蛋白可能是卵巢卵泡功能的新型调节因子。

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