Discovery of eCG
eCG is discovered by Harold Cole and George Hart when they realize that injecting serum from pregnant mares into immature rats induced their sexual maturity. The bioactive component in serum mediating these effects is termed pregnant mare serum gonadotropin, or PMSG.
Harold Cole and R. F. Miller show that PMSG can induce ovulation and oestrum in ewes during the anoestrous period, i.e. outside the breeding season, showing its potential for use in farming.
An international standard for PMSG is established. Shortly afterwards the sale of pharmaceutical preparations of PMSG commences. It is originally marketed for women but is later discontinued for that purpose. It however continues to be sold for animals, initially mainly for research, but increasingly for practical uses as evidence of efficacy from research accumulates.
Cole and Harold Goss find out that PMSG is produced and secreted by the endometrial cups, ulcer-like protuberances surrounding the foetus at the surface of the endometrium early in pregnancy. Their origins are unclear but are thought to be maternal.
Robert Moor and W.R. Allen realize that the endometrial cups are in fact of embryonic origin as the chorionic girdle is their progenitor. The chorionic girdle is a thick band of trophoblast which surrounds the conceptus between days 25 and 35 in pregnancy. This led to PMSG being renamed with its current nomenclature, to equine chorionic gonadotropin, or eCG.
Production of eCG starts in Iceland.
eCG is an important component in veterinary drugs, used worldwide for induction and synchronization of ovulation in animals, both farmed and wild.
The eCG molecule
eCG (equine chorionic gonadotropin) is a glycoprotein hormone with gonad-stimulating activity.
Other gonadotropins include FSH (follicle-stimulating hormone) and LH (luteinizing hormone). They are produced by the pituitary, while eCG is produced by the placenta.
FSH and LH act in synergy to stimulate ovulation and follicular growth, making them essential for fertility and reproduction.
eCG is structurally similar to eLH (equine LH) and thereby acts as an agonist for the LH receptor in horses.
eCG and eLH are mainly distinguished by glycosylation, as eCG is the most extensively glycosylated of all known glycoprotein hormones in mammals.
This extensive glycosylation makes eCG very stable, with a long half-life in blood.
When injected to almost all other mammals, eCG not only binds to the LH receptor, but also to the FSH receptor, giving it the unique ability to mediate both FSH- and LH-like activity in other animals.
The reason behind this double functionality is unknown, although eCG’s extensive glycosylation likely plays a role.
The double FSH- and LH-like functionality and high stability of eCG makes it very desirable for use in reproductive veterinary medicine.
Secretion into blood of pregnant mares
Around day 25 of gestation in mares, the allantois and chorion fuse and form the allantochorion. This leads to formation of the chorionic girdle, which develops at the junction between the enlarging allantochorion and the regressing yolk sac.
The chorionic girdle is a thick band of trophoblast cells and surrounds the conceptus until day 35-38 of gestation. By then, the chorionic girdle cells have proliferated and become mostly binucleate, and they then disassociate from other embryonic membranes and invade the endometrial epithelium.
Upon entering the epithelial stroma the cells stop proliferating and lose their ability to migrate, they enlarge, and terminally differentiate into endometrial cup cells, forming the endometrial cups.
As this happens, between days 38 and 40 of gestation, the endometrial cup cells begin to secrete eCG, and it can be detected in the pregnant mare’s blood.
The endometrial cups reach their maximum activity and eCG its maximal concentration in blood around days 70-80 of gestation, but around that time the cups start degrading until they are completely destroyed.
The amount of eCG secreted varies considerably between mares, both in regard to its concentration and to how long it is secreted in significant quantity.
Role of eCG in mares
The role of eCG in mares is not completely understood.
Its most likely role is to induce supplementary ovulation and/or luteinization of follicles and thereby maintain progesterone production and pregnancy until the placenta takes over that role.
Despite seemingly helping to maintain pregnancy, it has still not been established whether eCG is necessary for successful horse pregnancy.