THE EQUINE PLACENTA AND EQUINE CHORIONIC-GONADOTROPIN - AN OVERVIEW

Chorionic gonadotrophins seem to be unique for primate and equid speci es. Unlike primates, the equine conceptus does not implant in the mate rnal uterine endometrium until around day 37 of pregnancy. At this tim e specialized cells of the trophoblast, organized in the embryonic gir dle, invade the endometrium and become established in the endometrial stroma, forming the so-called endometrial cups. This migration of gird le cells is accompanied by their morphological transformation into lar ge decidual-like cells and by the appearance of a gonadotrophic hormon e in the mare's blood. There is convincing evidence today that the hor mone is of chorionic origin; therefore the term equine Chorionic Gonad otrophin (eCG) seems to be more appropriate than the formerly used ter m Pregnant Mare Serum Gonadotrophin (PMSG). Secretion of eCG peaks bet ween days 60 and 80 in pregnant mares, to decline gradually until day 130 of gestation, with pronounced inter-individual variation. There ap pear to be no hormonal regulatory mechanisms controlling eCG synthesis and secretion, suggesting that the size and the morphology of the end ometrial cups are the limiting factors. Equine CG is a glycoprotein ho rmone, composed of noncovalently bound alpha- and beta-subunits, The a lpha-subunit consists of 96 amino acids and is identical for eCG and t he pituitary hormones eLH, eFSH, and eTSH. The beta-subunit is similar to beta-hCG in that both have a C-terminal extension. It is comprised of 149 amino acids and the peptide primary structure is identical to that of beta-eLH. The differences between eLH and eCG appear to be due to different glycoslylation. Equine CG is the most heavily glycoslyat ed of all known mammalian glycoprotein hormones, with a sugar content of about 45% of the total molecular mass. Apart from commonly found N- linked oligosaccharides, the P-subunit contains 4 to 6 O-linked carboh ydrate chains which seem to be specific for chorionic gonadotrophins. Among the N-linked oligosaccharides a N-acetyllactosamine polymer has been identified which seems to be unique to eCG. The most striking qua ntitative aspect of eCG glycosylation is the extremely high sialic aci d content, including some disialodiantennary chains which render the h ormone relatively resistant to neuraminidase hydrolysis. Horse CG bind s to LH receptors from horse and other mammalian tissues and has biolo gical activities similar to LH, which is not surprising considering th e close similarity to eLH. However, the most unusual property of eCG i s its unique FSH-like biological activity when given to any mammal oth er than the horse. All the information available today suggests that t he dual activity of eCG in non-equids results from binding of the horm one to both FSH and LH receptors and acting as a potent hormone agonis t both in vitro and in vivo. The structural basis for the dual hormona l activity is still poorly understood. The carbohydrate composition, s ome unique amino acid transpositions, or the structure of the determin ant loop between amino acids 93 and 100 of the beta-subunit have been implied in the unusual FSH-receptor binding activity of eCG. The FSH-l ike properties of eCG have led to its wide scale use as a convenient e xogenous hormone preparation for the stimulation of follicular growth and superovulation in a large number of laboratory and farm animals. H owever its biological role in the horse is still a matter of controver sial discussion. Opinions range from its being redundant for maintaini ng equine pregnancy and a mere relic of evolution, to its being indisp ensible for a normal pregnancy as it induces and supports secondary co rpora lutea, possibly stimulates the fetal gonads, and may be involved in the control of the immune system.