title: Tumour necrosis factor alpha up-regulates matrix metalloproteinase-2 activity in periovulatory ovine follicles: metamorphic and endocrine implications.
abstract: The collagenous matrix of the wall of periovulatory follicles is degraded and remodelled during ovulatory ovarian rupture and luteinization. Matrix metalloproteinase-2 (MMP-2) belongs to a family of zinc endopeptidases that cleave extracellular proteins; its primary substrate is the type IV collagen of basement membranes. Tumour necrosis factor alpha (TNFalpha) is a putative mediator of collagenolysis and ovulation. The objective of this investigation was to ascertain the regulatory role of TNFalpha on MMP-2 activity relevant to the folliculo-luteal transition in ewes. Luteal regression and the preovulatory surge of gonadotropins were induced by administration of prostaglandin F2alpha and gonadotropin-releasing hormone (GnRH) on Days 14 and 15.5 (= 0 h) of the oestrous cycle, respectively. Ovulation occurs from the dominant follicle approximately 24 h after GnRH. An immunocapture-activity assay was used to measure MMP-2 in follicular extracts. Bioactive MMP-2 increased from 0 to 20 to 40 h after GnRH. Enzyme was immunolocalized at 40 h to the connective tissue framework that invades the parenchyma of the formative corpus luteum. Activity of MMP-2 was up-regulated by incubation (20 h) of 0-h follicular explants with TNFalpha; this response was suppressed by the transcriptional inhibitor actinomycin D. Activity of MMP-2 was reduced when preovulatory follicular tissues were incubated (12-h explants for 6 h) with TNFalpha antiserum. Ovulation was blocked by intrafollicular injection of TNFalpha antiserum. Unruptured follicles luteinized, but were deficient in collagenous/vascularized trabeculae, and produced less progesterone than their control luteal counterparts. It is suggested that TNFalpha, via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum.
authors.affiliation: Department of Animal Science, University of Wyoming, Laramie 82071, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Gottsch
authors.forename: E A
authors.initials: EA
authors.lastname: Van Kirk
authors.forename: W J
authors.initials: WJ
authors.lastname: Murdoch
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007106:Immune Sera / Q000494:pharmacology; D003341:Luteolysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects / Q000201:enzymology*; D010060:Ovulation / Q000187:drug effects; D012756:Sheep / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
chemical_list: D007106:Immune Sera; D019384:Nucleic Acid Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007987:Gonadotropin-Releasing Hormone; D003094:Collagen; D015237:Dinoprost; D020778:Matrix Metalloproteinase 2