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Citation
Tags
HERO ID
6963030
Reference Type
Journal Article
Title
Intact follicular maturation and defective luteal function in mice deficient ford cyclin-dependent kinase-4
Author(s)
Moons, DS; Jirawatnotai, S; Tsutsui, T; Franks, R; Parlow, AF; Hales, DB; Gibori, G; Fazleabas, AT; Kiyokawa, H; ,
Year
2002
Is Peer Reviewed?
Yes
Journal
Endocrinology
ISSN:
0013-7227
EISSN:
1945-7170
Publisher
ENDOCRINE SOC
Location
WASHINGTON
Page Numbers
647-654
PMID
11796521
Web of Science Id
WOS:000173437000037
Abstract
Cell cycle progression of granulosa cells is critical for ovarian function, especially follicular maturation. During follicular maturation, FSH induces cyclin D2, which promotes G(1) progression by activating cyclin-dependent kinase-4 (Cdk4). Because cyclin D2-deficient mice exhibit a block: in follicular growth, cyclin D2/Cdk4 has been hypothesized to be required for FSH-dependent proliferation of granulosa cells., Here we investigate ovarian function in Cdk4-knockout mice we recently generated. Cdk4(-/-) females were sterile, but the morphology of their ovaries appeared normal before sexual maturation. The number of preovulatory follicles and the ovulation efficiency were modestly reduced in gonadotropin-treated Cdk4(-/-) mice. However, unlike cyclin D2-deficient mice, Cdk4(-/-) mice showed no obvious defect in FSH-induced proliferation of granulosa cells. Cdk4(-/-) ovaries displayed normal preovulatory expression of aromatase, PR, and cyclooxygenase-2. Postovulatory progesterone secretion was markedly impaired in Cdk4(-/-) mice, although granulosa cells initiated luteinization with induction of p450 side-chain cleavage cytochrome and p27(Kip1). Progesterone treatment rescued implantation and restored fertility in Cdk4(-/-) mice. Serum PRL levels after mating were significantly reduced in Cdk4(-/-) mice, suggesting the involvement of perturbed PRL regulation in luteal failure. Thus, Cdk4 is critical for luteal function, and some redundant protein(s) can compensate for the absence of Cdk4 in proliferation of granulosa cells.
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