Role of ERK1/2 in FSH induced PCNA expression and steroidogenesis in granulosa cells.
Follicular development is characterized by both proliferation and differentiation of granulosa cells (GCs) under the control of FSH. However, the cellular mechanism by FSH is not known. Using cultured GCs, we examined whether FSH activated ERK1/2 was involved in the regulation of the proliferation related gene proliferating cell nuclear antigen (PCNA) and steroidogenesis. GCs were obtained from the ovaries of DES treated immature rats and cultured in serum free medium. The results showed that FSH activated ERK1/2 in a time dependent manner, with a peak at 20 min. Such activation was PKA dependent as was inhibited by specific inhibitors. FSH induced PCNA expression in a time dependent manner, with a maximum stimulation at 2 h. Similarly, StAR and steroid levels increased as FSH treatment time extended, with a maximum progesterone and StAR production at 48 h. ERK1/2 inactivation by UO126 inhibited the stimulatory effects of FSH on both PCNA and StAR expression and steroid synthesis in the GCs (p less than 0.01). Immunocytochemical studies further revealed that ERK1/2 inhibition led to a reduction of mitochondrial StAR in the GCs by FSH. These observations suggested that the stimulation of FSH on PCNA expression and steroidogenesis in GCs was mediated at least partially by ERK1/2.
Yu
Fu-Qing
FQ
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.
Han
Chun-Sheng
CS
Yang
Wei
W
Jin
Xuan
X
Hu
Zhao-Yuan
ZY
Liu
Yi-Xun
YX
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism*; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D010750:Phosphoproteins; D018809:Proliferating Cell Nuclear Antigen; C113580:U 0126; D000098682:Steroidogenic Acute Regulatory Protein; D005640:Follicle Stimulating Hormone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3