
%0 Journal Article
%A Gottsch, Michelle L. 
%A Van Kirk, Edward A. 
%A Murdoch, William J. 
%T Tumour necrosis factor alpha up-regulates matrix metalloproteinase-2 activity in periovulatory ovine follicles: metamorphic and endocrine implications
%J Reproduction, Fertility and Development
%D 2000/11/14
%V 12
%N 2
%P 75-80
%K corpus luteum, luteinized unruptured follicle, progesterone, sheep, type IV collagen.
%R https://doi.org/10.1071/RD00054
%U https://www.publish.csiro.au/paper/RD00054 
%X 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 &#945; (TNF&#945;) is a putative mediator of collagenolysis and ovulation. The objective of this investigation was to ascertain the regulatory role of TNFa 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 F 2 &#945; 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 TNF&#945;; 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 TNF&#945; antiserum. Ovulation was blocked by intrafollicular injection of TNF&#945; antiserum. Unruptured follicles luteinized, but were deficient in collagenous/vascularized trabeculae, and produced less progesterone than their control luteal counterparts. It is suggested that TNF&#945;, via MMP-2 induction, contributes to the reorganization of an ovulatory follicle into a fully competent corpus luteum. 
