Kakuta Hanako, Iguchi Taisen, Sato Tomomi
Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan.
Graduate School of Nanobioscience, Yokohama City University, Yokohama, Japan
In Vivo. 2018 Nov-Dec;32(6):1387-1401. doi: 10.21873/invivo.11391.
BACKGROUND/AIM: Theca cells produce androgen by 17α-hydroxylase-17,20-lyase encoded by Cyp17a1, and conversion of androgen to estrogen in granulosa cells is regulated by gonadotropins. Women with polycystic ovarian syndrome (PCOS) exhibit elevated levels of androgens due to high Cyp17a1 expression and alterations in gene expression in granulosa cells. The aim of this study was to examine the interaction between theca and granulosa cells in PCOS-model mice.
To produce PCOS-model mice, neonatal mice were injected with 1 μg TP for 3 days from the day of birth. Gonadotropins were injected according to the superovulation protocol to 3-month-old control mice and PCOS-model mice. Histological changes and expression of genes involved in steroidogenesis, ovulation and luteinization were investigated by immunohistochemistry and real-time RT-PCR, respectively.
Pregnant mare serum gonadotropin (PMSG) induced the expression of genes involved in steroidogenesis in control prepubertal mice, whereas human chorionic gonadotropin (hCG) reduced Cyp17a1 expression and induced phospho-ERK1/2 in granulosa cells. Cyp17a1 was reduced in PMSG-primed PCOS-model mice regardless of hCG injection, and PMSG induced phosphorylation of ERK1/2 in granulosa cells.
Phospho-ERK1/2 in granulosa cells can be correlated with reduced Cyp17a1 expression in theca cells, and the interaction between granulosa and theca cells may be impaired in PCOS-model mice.
背景/目的:卵泡膜细胞通过由Cyp17a1编码的17α-羟化酶-17,20-裂解酶产生雄激素,而颗粒细胞中雄激素向雌激素的转化受促性腺激素调节。多囊卵巢综合征(PCOS)女性由于Cyp17a1高表达以及颗粒细胞基因表达改变而表现出雄激素水平升高。本研究的目的是检测PCOS模型小鼠中卵泡膜细胞与颗粒细胞之间的相互作用。
为制备PCOS模型小鼠,新生小鼠自出生日起连续3天注射1μg睾酮丙酸酯(TP)。按照超排卵方案给3月龄对照小鼠和PCOS模型小鼠注射促性腺激素。分别通过免疫组织化学和实时逆转录-聚合酶链反应(RT-PCR)研究类固醇生成、排卵和黄体化相关基因的组织学变化及表达情况。
孕马血清促性腺激素(PMSG)诱导对照青春期前小鼠中参与类固醇生成的基因表达,而人绒毛膜促性腺激素(hCG)降低颗粒细胞中Cyp17a1表达并诱导细胞外信号调节激酶1/2(ERK1/2)磷酸化。无论是否注射hCG,PMSG预处理的PCOS模型小鼠中Cyp17a1均降低,且PMSG诱导颗粒细胞中ERK1/2磷酸化。
颗粒细胞中的磷酸化ERK1/2可能与卵泡膜细胞中Cyp17a1表达降低相关,且PCOS模型小鼠中颗粒细胞与卵泡膜细胞之间的相互作用可能受损。