Regulation by 3,5,3′-tri-iodothyronine and FSH of cytochrome P450 family 19 (CYP19) expression in mouse granulosa cells
Juan Liu A D , Yingying Han B , Ye Tian A , Xuechun Weng A , Xusong Hu A , Wenbo Liu A , Dai Heng A , Kaili Xu A , Yanzhou Yang C E and Cheng Zhang A E
+ Author Affiliations
- Author Affiliations
A College of Life Science, Capital Normal University, Beijing 100048, P.R. China.
B College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing 100083, P.R. China.
C Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, Ningxia Medical University, Ningxia 750004, P.R. China.
D State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P.R. China.
E Corresponding author. Email: zhch8012@163.com
Reproduction, Fertility and Development 30(9) 1225-1233 https://doi.org/10.1071/RD17362
Submitted: 10 September 2017 Accepted: 26 February 2018 Published: 9 April 2018
Abstract
Cytochrome P450 family 19 (CYP19) plays an important role in follicular development, which is regulated by FSH. Although 3,5,3′-tri-iodothyronine (T3) combines with FSH to induce preantral follicle growth and granulosa cell development, the mechanism involved remains unclear. The aim of the present study was to determine the cellular and molecular mechanisms by which thyroid hormone (TH) and FSH regulate CYP19 expression and sterol biosynthesis during preantral follicle growth. Mice were injected subcutaneously (s.c.) with eCG (Equine chorionic gonadotropin). The results showed that eCG increased CYP19 expression in ovarian cells. CYP19 expression in granulosa cells was increased after FSH treatment, and this response was enhanced by T3. Knockdown of CYP19 significantly decreased granulosa cell viability and hormone-stimulated proliferation. In addition, CYP19 knockdown also blocked T3- and FSH-induced oestradiol (E2) synthesis in granulosa cells. Furthermore, activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was required for T3 and FSH regulation of CYP19 expression. In conclusion, the results of the present study indicate that CYP19 is important for T3- and FSH-induced granulosa cell development in the early stages. CYP19 could be a downstream effector of the PI3K/Akt pathway in regulating TH and FSH during follicular development and sterol biosynthesis. The findings suggest that CYP19 is a novel mediator of T3- and FSH-induced follicular development.
Additional keywords: steroid hormone.
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