Expression of tissue inhibitor of metalloproteinases-1 in the primate ovary during induced luteal regression

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 F-2 alpha analogue. Ovaries from different stages of the normal ovarian cycle were also studied. Expression of TIMP-1 war 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 F-2 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 consistent with an additional function of TIMP-1 facilitator of steroidogenesis.