NONHUMAN PRIMATE MODELS - ARTIFICIAL MENSTRUAL CYCLES, ENDOMETRIAL MATRIX METALLOPROTEINASES AND SC ENDOMETRIAL GRAFTS

Rhesus monkeys are useful models in which to examine the hormonal regu lation of endometrial matrix metalloproteinases (MMP) and to evaluate the role of MMP in uterine bleeding, Artificial 28 day menstrual cycle s can be induced in ovariectomized monkeys by inserting an oestradiol implant for 2 weeks, then inserting a progesterone implant for 2 weeks , and then, with the oestradiol implant remaining in place, removing a nd reinserting the progesterone implant at 2 week intervals, To examin e MMP during menses, we established such cycles and removed uteri by h ysterectomy at closely spaced intervals before, during and after mense s, as well as at later time points, Some samples were also obtained du ring menses induced by the withdrawal of both progesterone and oestrad iol, We examined mRNA of the following MMP by Northern blotting: matri lysin, stromelysin-1, stromelysin-2, stromelysin-3 and the tissue inhi bitor of MMP TIMP-1. The expression of these MMP mRNA increased substa ntially by 2-3 days after progesterone withdrawal, whether or not oest radiol was maintained. The expression of some of the MMP (stromelysins -1 and -2) returned very rapidly to baseline levels by 5 days after pr ogesterone withdrawal, while the expression of others (matrilysin, str omelysin-3 and TIMP-1) declined more slowly, reaching a baseline level by 10 days after progesterone withdrawal, with little or no further d ecline after progesterone concentrations rose during the induced lutea l phase, Immunocytochemical studies showed that matrilysin was express ed primarily in the glands of the upper functionalis. In other work wi th the rhesus monkey model, we used a s. c. endometrial autograft tech nique in which pieces of endometrium were autotransplanted to the abdo minal skin, During menses in the grafts, matrilysin was expressed in t he glands of the grafts similar to the glands in the eutopic endometri um. Endometrial autografts can serve as a useful model for the study o f MMP in uterine bleeding.