title: Expression of tissue inhibitor of metalloproteinases-1 in the primate ovary during induced luteal regression.
abstract: Although tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the major secretory products of the corpus luteum, the functional significance of this is not clear. In addition to its role as a specific inhibitor of the matrix metalloproteinase enzymes involved in tissue remodelling, it has recently been suggested that TIMP-1 is also a potent stimulator of steroidogenesis in vitro. However, in the ruminant, TIMP-1 expression increases during luteal regression. This study sought to determine (i) the effect of induced luteal regression on ovarian TIMP-1 expression in the primate and (ii) the expression of TIMP-1 in other steroidogenic and non-steroidogenic tissues. Marmoset ovaries were studied on day 10 of the normal luteal phase and 12 and 24 h after induced luteolysis, with either gonadotrophin-releasing hormone (GnRH) antagonist or prostaglandin F2 alpha analogue. Ovaries from different stages of the normal ovarian cycle were also studied. Expression of TIMP-1 was investigated by isotopic in situ hybridisation. TIMP-1 expression was also examined in a wide range of other marmoset tissues by Northern blotting and in situ hybridisation. TIMP-1 was found to be highly expressed in the marmoset corpus luteum. Luteolysis induced with either prostaglandin F2 alpha or GnRH antagonist was associated with a significant fall in TIMP-1 expression in luteal tissue. TIMP-1 mRNA was also localised to ovarian follicles throughout the ovarian cycle. Expression occurred in the thecal layer of smaller follicles (< 1.5 mm) and the granulosal layer of larger pre-ovulatory follicles. In atretic follicles, TIMP-1 was highly expressed at the interface between the thecal and granulosal cells. TIMP-1 was found to be predominantly expressed in steroidogenic tissues, particularly the ovary, adrenal and placenta. These data support a role for changes in TIMP-1 expression in tissue remodelling in the ovary and are consistent with an additional function of TIMP-1 as a facilitator of steroidogenesis.
authors.affiliation: MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
authors.forename: W C
authors.initials: WC
authors.lastname: Duncan
authors.forename: P J
authors.initials: PJ
authors.lastname: Illingworth
authors.forename: H M
authors.initials: HM
authors.lastname: Fraser
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002144:Callithrix; D003008:Cloprostenol / Q000494:pharmacology; D003338:Corpus Luteum / Q000378:metabolism; D005260:Female; D005496:Follicular Atresia / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D003341:Luteolysis / Q000378:metabolism*; D010053:Ovary / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011480:Protease Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D006023:Glycoproteins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D007987:Gonadotropin-Releasing Hormone; D003008:Cloprostenol