earticle

영어

Equine-chorionic gonadotropin (eCG) is a member of the glycoprotein family with LH, FSH and TSH. In non-equid species, eCG shows both LH- and FSH-like activities except the horses and has a high affinity for both FSH and LH receptors. These receptors were synthesized in granulosa/theca and Sertoli/Leydig cells in ovary/testis and tansported to the membrane surface. Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. The LH/CGR is a member of the family of G-protein-coupled receptors that the receptor was composed of a single polypeptide chain. To assess the functional effect of the D576Y mutation in the eLH/CGR, wild type and mutated equine LH/CGR were transiently expressed in CHO-K1 cells and cAMP accumulation was measured. rec-eCG produced a concentration-dependent increase in cAMP production in cells expressing the wild-type eLH/CGR, with an EC50 of 21.3 ng /mL and mean maximal stimulation (170.1±11.9 nM). However, the mutant eLH/CGR -D576Y produced a 6.4-fold increase in basal cAMP production in CHO-K1 cells, indicating that it was constitutively active. In the inactivating mutant (R464H), cAMP responsiveness was completely flat. But cAMP concentration for activating m mutant (M- 398T) was almost same pattern as wild-type receptor. Thus, our result suggest that an inherited disease FMPP is due to a constitutively activating mutations in a G-protein coupled hormone receptor.