The gonadotropin-releasing hormone family of neuropeptides in the brain ofhuman, bovine and rat: identification of a third isoform

The mammalian gonadotropin-releasing hormone (GnRH-I), which regulates repr oduction, was the first isoform of GnRH that was identified in mammals. Rec ently, me and others hale demonstrated the existence of a second isoform of GnRH in the brain of mammals. The presence of a third isoform of GnRH, GnR H-III, in the brain of mammals is reported herein. GnRH-III, extracted from the brain of bovine and human, was purified by high performance liquid chr omatography, using two distinct elution programs. In both, GnRH-III nas elu ted at the same positions as synthetic salmon GnRH, as demonstrated by radi oimmunoassay. The luteinizing hormone-releasing activity of purified GnRH-I II, using dispersed rat pituitary cells, was found to be similar to that of synthetic salmon GnRH. The total amount of GnRH-III, determined by radioim munoassay, in the hypothalamus and midbrain of humans and calves is similar to that of GnRH-I, Immunohistochemical studies demonstrated GnRH-III-conta ining neurons in the hypothalamus and midbrain of human and GnRH-III fibers in the median eminence of rats. The distribution of GnRH-III in the brain suggests that in addition to a putative function as a neurohormone at the h ypothalamic-pituitary axis, GnRH-III may have other functions. Our present results suggest that multiple isoforms of GnRH are present in the brain of mammals, and further studies are required in order to elucidate their biolo gical functions. (C) 1999 Federation of European Biochemical Societies.