The pregnancy-associated glycoproteins (PAGs) were first described as placental antigens of cattle that were also present in the blood serum of the mother after implantation. Molecular cloning studies have shown that they are members of the aspartic proteinase gene family and closely related to the pepsinogens. An enzymatic role seems unlikely, as at least some of them have mutations likely to render them enzymatically inactive. Nevertheless, these molecules have retained the substrate-binding cleft of the pepsins and are expressed abundantly in trophectoderm, particularly in the invasive binucleate cell component. There may be as many as 100 PAG genes in cattle and sheep, many of which are transcribed. PAGs are also products of the placenta of the pig, a species whose progenitors diverged from the ruminants at least 55 million years ago. There is even evidence for PAG-like molecules outside the Artiodactyla. Although their function remains elusive, it seems unlikely that these placentally expressed molecules are simply oddities in view of their long-term evolutionary survival and conspicuous presence at the fetal-maternal interface.
JA Green, S Xie and RM Roberts
CS Rosenfeld, JS Wagner, RM Roberts and DB Lubahn
Oestrogen regulates several hypothalamic and pituitary hormones, which in turn control ovarian functions. Oestrogen and its metabolites, such as catecholoestrogens, also have direct effects within the ovary. This review examines the roles of oestrogen in regulating ovarian folliculogenesis, ovulation and corpus luteum formation. Oestrogen promotes follicular development, which culminates in ovulation, by potentiating follicular development, granulosa cell expression of gonadotrophin receptors, steroidogenesis, and gap junction formation by granulosa cells, and by inhibiting granulosa cell apoptosis. In addition, oestrogen may be needed for corpus luteum formation and maintenance. Studies on mutant mice that either lack one or both of the known oestrogen receptors or are unable to synthesize oestrogen support some but not all of these prior inferences of the roles of oestrogen within the ovary. Although these transgenic mice have proved useful in determining some of the intraovarian actions of oestrogen, they present confounding problems, including hormonal imbalances, that hinder interpretation. Transgenic mice with conditional or tissue-directed mutations in their oestrogen receptors are needed to dissect the ovarian actions of oestrogen further. In addition, microarray technologies, combined with specific hormone treatment regimens are likely to provide an attractive, alternative approach to using mutant mice in clarifying the direct actions of oestrogen in the ovaries of other species.