title: Localization and temporal regulation of tissue inhibitor of metalloproteinases-4 in mouse ovary.
abstract: Tissue inhibitors of metalloproteinases (TIMPs) are potential regulators of tissue remodeling in the ovary. The aim of the present study was to examine the localization and temporal regulation of TIMP-4 protein in the mouse ovary. An induced superovulation model (eCG/hCG) was employed in immature mice to evaluate TIMP-4 protein expression profiles in ovaries collected during the follicular phase, the pre ovulatory period, and the luteal lifespan. Immunofluorescence results indicated that TIMP-4 protein was localized to theca of both antral and preovulatory follicles and adjacent ovarian stroma. After the initiation of luteinization with hCG, TIMP-4 was observed within the luteinizing granulosa cells and persisted throughout the lifespan of the corpus luteum. In the cycling ovary, TIMP-4 signaling localized to corpus luteum from previous estrous cycles, the theca of preovulatory follicles, and appeared to be lower in newly forming corpus luteum. Western analysis further showed that the levels of TIMP-4 increased significantly during the luteinization process of granulosa cells, but no significant change was found among all corpus luteum stages. A putative regulatory mechanism of TIMP-4 expression was identified utilizing an in vitro model. Treatment of cultured granulosa cells with hCG significantly augmented TIMP-4 protein expression levels. Together our data indicate that the luteinization process of granulosa cells is associated with up-regulation of TIMP-4 and that TIMP-4 might play an essential role in maintenance of the luteal function during the whole lifespan of corpus luteum.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Bu
authors.forename: Chenfu
authors.initials: C
authors.lastname: Cao
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yang
authors.forename: Chenglin
authors.initials: C
authors.lastname: Miao
authors.forename: Zeng
authors.initials: Z
authors.lastname: Hu
authors.forename: Yujing
authors.initials: Y
authors.lastname: Cao
authors.forename: Qingxiang Amy
authors.initials: QA
authors.lastname: Sang
authors.forename: Enkui
authors.initials: E
authors.lastname: Duan
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000737:chemistry / Q000378:metabolism; D030762:Estrous Cycle; D005260:Female; D008184:Luteal Cells / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000737:chemistry* / Q000378:metabolism; D010060:Ovulation; D017154:Stromal Cells / Q000737:chemistry; D013480:Superovulation; D013799:Theca Cells / Q000737:chemistry; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D006063:Chorionic Gonadotropin; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4