Extragonadal actions of chorionic gonadotropin

The primary embryonic signal in primates is chorionic gonadotropin (CG, designated hCG in humans), that is classically associated with corpus luteum rescue and progesterone production. However, research over the past decade has revealed the presence of the hCG receptor in a variety of extragonadal tissues. Additionally, discoveries of the multiple variants of hCG, namely, native hCG, hyperglycosylated hCG (hyp-hCG) and the beta- subunit of the hyperglycosylated hCG (hCG-free beta) has established a role for extragonadal actions of hCG. For the initiation and maintenance of pregnancy, hCG mediates multiple placental, uterine and fetal functions. Some of these include development of syncytiotrophoblast cells, mitotic growth and differentiation of the endometrium, localized suppression of the maternal immune system, modulation of uterine morphology and gene expression and coordination of intricate signal transduction between the endometrium. Recurrent pregnancy loss, pre-eclampsia and endometriosis are associated with altered responses of hCG, all of which have a detrimental effect on pregnancy. A role for hyp-hCG in mediating the development of both trophoblastic and non-trophoblastic tumors has also been suggested. Other significant non-gonadal applications of hCG include predicting preeclampsia, determining the risk of Down's syndrome and gestational trophoblastic disease, along with relaxing myometrial contractility and preventing recurrent miscarriages. Presence of hCG free-beta in serum of cancer patients enables its usage as a diagnostic tumor marker. Thus, the extragonadal functions of hCG encompasses a wide spectrum of applications and is an open area for continued investigation.