Progesterone is a pleiotropic regulator of uterine function required for the maintenance of pregnancy in mammals. A major action of progesterone is to induce expression of genes encoding for secretory proteins of the uterine endometrium. These proteins participate in several roles deemed essential for survival of the conceptus and include enzymes, transport proteins, and regulatory proteins. Several serpins have been identified as being part of the milieu of secretory proteins in the progesterone-dominated uterus. Among these are plasminogen activator inhibitor-1, induced by progesterone in cultured human endometrial cells (Miyauchi et al., 1995; Lockwood et al., 1995), and α1-antitrypsin, which is synthesized by human endometrium during pregnancy (Fay et al., 1990) and also can enter uterine fluid as a serum transudate (Bany and McRae, 1992). These proteins likely inhibit serine proteinases secreted by the uterus and placenta and may limit remodeling of the endometrium, participate in local hemostasis and regulate placental invasiveness. In addition to these well-known serpins, the uterus of certain species of ungulates each produce one or more members of a subfamily of serpins that are characterized by endometrial site of synthesis, sequence homology to each other, and weak or no known antiproteinase activity. This chapter will concentrate on the most well-characterized of these uterine-specific serpins — a glycoprotein of the sheep uterus called uterine milk protein (UTMP) — and will compare the properties of this protein to other uterine serpins. Uterine milk protein is the most abundant steroid-induced protein yet described and gram quantities can be obtained from the uterus of a single unilaterally-pregnant ewe (Moffatt et al., 1987a). There is evidence to implicate UTMP in inhibition of lymphocyte funciton and in binding interactions with placental secretory proteins. It is also possible that UTMP acts as a carrier protein to transport maternal products across the placenta.KeywordsUterine EndometriumUterine FluidReactive Center LoopInfer Amino Acid SequencePlacental InvasivenessThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.