title: Regulated expression of ADAMTS family members in follicles and cumulus oocyte complexes: evidence for specific and redundant patterns during ovulation.
abstract: Protease cascades are essential for many biological events, including the LH-induced process of ovulation. ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin-like repeats-1) is expressed and hormonally regulated in the ovary by LH and the progesterone receptor. To determine whether other family members might be expressed and regulated in the rodent ovary, those closely related to ADAMTS1 (ADAMTS4 and ADAMTS5) were analyzed in the mouse ovary by reverse transcription-polymerase chain reaction as well as by Western blot, immunohistochemical, and immunocytochemical analyses using highly specific antibodies. Prior to ovulation, ADAMTS4 and ADAMTS5 were coexpressed in granulosa cells of most follicles, whereas ADAMTS5 was also present in granulosa cells of atretic follicles. Following ovulation, ADAMTS1 and ADAMTS4 (but not ADAMTS5) were expressed in multiple cell types, including those within the highly vascular ovulation cone that marks the site of follicle rupture, endothelial cells of newly forming corpora lutea, and cumulus cells within the ovulated cumulus cell-oocyte complex (COC). Versican, a substrate for ADAMTS1 and ADAMTS4, colocalized with these proteases and hylauronan on the cumulus cell surface. To further characterize induction of these proteases and associated molecules, COCs and granulosa cells were isolated from preovulatory follicles and treated with FSH. In expanded COCs and differentiated granulosa cells, FSH induced expression of ADAMTS4 and versican message and protein, whereas increased levels of ADAMTS1 protein was observed in the media of granulosa cells where it was stabilized by heparin in this in vitro system. These studies provide the first evidence that ADAMTS1, ADAMTS4, and ADAMTS5 are expressed in spatiotemporal patterns that suggest distinct as well as some overlapping functions that relate to the broad expression pattern of versican in granulosa cells of small follicles, expanded COCs, and endothelial cells of the mouse ovary.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. joanner@bcm.tmc.edu
authors.forename: JoAnne S
authors.initials: JS
authors.lastname: Richards
authors.forename: Immaculada
authors.initials: I
authors.lastname: Hernandez-Gonzalez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gonzalez-Robayna
authors.forename: Eva
authors.initials: E
authors.lastname: Teuling
authors.forename: Yuet
authors.initials: Y
authors.lastname: Lo
authors.forename: Derek
authors.initials: D
authors.lastname: Boerboom
authors.forename: Allison E
authors.initials: AE
authors.lastname: Falender
authors.forename: Kari H
authors.initials: KH
authors.lastname: Doyle
authors.forename: Richard G
authors.initials: RG
authors.lastname: LeBaron
authors.forename: Vivian
authors.initials: V
authors.lastname: Thompson
authors.forename: John D
authors.initials: JD
authors.lastname: Sandy
mesh_terms: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D001483:Base Sequence; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000187:drug effects / Q000201:enzymology*; D006080:Ovarian Follicle / Q000187:drug effects / Q000201:enzymology*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D010060:Ovulation / Q000235:genetics* / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D053667:Syndecans
chemical_list: D019483:Disintegrins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D053667:Syndecans; D005640:Follicle Stimulating Hormone; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000071116:ADAMTS5 Protein; C486323:Adamts1 protein, mouse; C498489:Adamts5 protein, mouse; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C498537:Mmp17 protein, mouse; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse