title: Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model.
abstract: Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells.
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Li-Sha
authors.initials: LS
authors.lastname: An
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Yuan
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Zi-Yun
authors.initials: ZY
authors.lastname: Shi
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Gui-Qing
authors.initials: GQ
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006107:Granulosa Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D010060:Ovulation; D010750:Phosphoproteins / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism*; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D053148:Caspase 3