title: Ovarian membrane-type matrix metalloproteinases: induction of MMP14 and MMP16 during the periovulatory period in the rat, macaque, and human.
abstract: An intrafollicular increase in proteolytic activity drives ovulatory events. Surprisingly, the periovulatory expression profile of the membrane-type matrix metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has not been extensively examined. Expression profiles of the MT-MMPs were investigated in ovarian tissue from well-characterized rat and macaque periovulatory models and naturally cycling women across the periovulatory period. Among the six known MT-MMPs, mRNA expression of Mmp14, Mmp16, and Mmp25 was increased after human chorionic gonadotropin (hCG) administration in rats. In human granulosa cells, mRNA expression of MMP14 and MMP16 increased following hCG treatment. In contrast, mRNA levels of MMP16 and MMP25 in human theca cells were unchanged before ovulation but declined by the postovulatory stage. In macaque granulosa cells, hCG increased mRNA for MMP16 but not MMP14. Immunoblotting showed that protein levels of MMP14 and MMP16 in rats increased, similar to their mRNA expression. In macaque granulosa cells, only the active form of the MMP14 protein increased after hCG, unlike its mRNA or the proprotein. By immunohistochemistry, both MMP14 and MMP16 localized to the different ovarian cell types in rats and humans. Treatment with hCG resulted in intense immunoreactivity of MMP14 and MMP16 proteins in the granulosa and theca cells. The present study shows that MMP14 and MMP16 are increased by hCG administration in the ovulating follicle, demonstrating that these MMPs are conserved among rats, macaques, and humans. These findings suggest that MT-MMPs could have an important role in promoting ovulation and remodeling of the ovulated follicle into the corpus luteum.
authors.affiliation: Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Muraly
authors.initials: M
authors.lastname: Puttabyatappa
authors.affiliation: Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Jacot
authors.affiliation: Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Linah F
authors.initials: LF
authors.lastname: Al-Alem
authors.affiliation: Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Rosewell
authors.affiliation: Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Duffy
authors.affiliation: Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Brännström
authors.affiliation: Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky tecurry@uky.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Curry
mesh_terms: D000818:Animals; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008252:Macaca fascicularis / Q000502:physiology*; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D053513:Matrix Metalloproteinase 16 / Q000235:genetics / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000201:enzymology*; D010060:Ovulation / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D059467:Transcriptome
chemical_list: D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D053513:Matrix Metalloproteinase 16; D053504:Matrix Metalloproteinases, Membrane-Associated; C403928:matrix metalloproteinase 25; D053511:Matrix Metalloproteinase 14
keywords: extracellular matrix; granulosa cells; matrix metalloproteinase; ovary; ovulation; theca cell