The equine placenta and equine chorionic gonadotrophin — an overview

Summary

Chorionic gonadotrophins seem to be unique for primate and equid species. Unlike primates, the equine conceptus does not implant in the maternal uterine endometrium until around day 37 of pregnancy. At this time specialized cells of the trophoblast, organized in the embryonic girdle, invade the endometrium and become established in the endometrial stroma, forming the so-called endometrial cups. This migration of girdle cells is accompanied by their morphological transformation into large decidual-like cells and by the appearance of a gonadotrophic hormone in the mare's blood. There is convincing evidence today that the hormone is of chorionic origin; therefore the term equine Chorionic Gonadotrophin (eCG) seems to be more appropriate than the formerly used term Pregnant Mare Serum Gonadotrophin (PMSG). Secretion of eCG peaks between days 60 and 80 in pregnant mares, to decline gradually until day 130 of gestation, with pronounced inter-individual variation. There appear to be no hormonal regulatory mechanisms controlling eCG synthesis and secretion, suggesting that the size and the morphology of the endometrial cups are the limiting factors.

Equine CG is a glycoprotein hormone, composed of noncovalently bound α- and β-subunits. The α-subunit consists of 96 amino acids and is identical for eCG and the pituitary hormones eLH, eFSH, and eTSH. The β-subunit is similar to β-hCG in that both have a C-ter-I minal extension. It is comprised of 149 amino acids and the peptide primary structure is identical to that of β-eLH. The differences between eLH and eCG appear to be due to different glycoslylation. Equine CG is the most heavily glycoslyated 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 β-subunit contains 4 to 6 O-linked carbohydrate 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 quantitative aspect of eCG glycosylation is the extremely high sialic acid content, including some disialodiantennary chains which render the hormone relatively resistant to neuraminidase hydrolysis.

Horse CG binds to LH receptors from horse and other mammalian tissues and has biological activities similar to LH, which is not surprising considering the close similarity to eLH. However, the most unusual property of eCG is its unique FSH-like biological activity when given to any mammal other than the horse. All the information available today suggests that the dual activity of eCG in non-equids results from binding of the hormone to both FSH and LH receptors and acting as a potent hormone agonist both in vitro and in vivo. The structural basis for the dual hormonal activity is still poorly understood. The carbohydrate composition, some unique amino acid transpositions, or the structure of the determinant loop between amino acids 93 and 100 of the β-subunit have been implied in the unusual FSH-receptor binding activity of eCG.

The FSH-like properties of eCG have led to its wide scale use as a convenient exogenous hormone preparation for the stimulation of follicular growth and superovulation in a large number of laboratory and farm animals. However its biological role in the horse is still a matter of controversial discussion. Opinions range from its being redundant for maintaining equine pregnancy and a mere relic of evolution, to its being indispensible for a normal pregnancy as it induces and supports secondary corpora lutea, possibly stimulates the fetal gonads, and may be involved in the control of the immune system.

Key words

mare - equine chorionic gonadotrophin - FSH-bioactivity - carbohydrate - sialic acid