GnRH i jego receptor 40-lecie ustalenia struktury pierwszorzędowej GnRH 100-lecie urodzin prof. Eugeniusza Domańskiego 90-lecie urodzin prof. Mariana Jutisza

Abstrakt

Determination for the first time, of primary structure of GnRH, by two independent research groups, released the very avalanche of research on the spectrum aspects concerning both the decapeptide and its receptor. Thirty (30) structural forms of natural GnRH were identified and determined in vertebrates and in invertebrates. In many vertebrates, three forms of GnRH and three cognate receptors were identified with distinct distributions and functions. Human hypothalamic GnRH regulates LH and FSH secretion through the pituitary GnRH type I receptor via activation of Gq. Studies identified amino acid residues both in the ligand and receptor involved in binding, receptor activation, and translation into intracellular signal transduction. The predominant binding of the GnRH type I receptor in the gonadotrope is through Gq stimulation, signal translation can be propagated also via other G proteins and potentially by G protein-independent means. The eventual selection of intracellular signaling may be specifically directed by differences in ligand structure. A second form of GnRH, GnRH II, conserved in all higher vertebrates including man, for more than 400 milions years of evolution, is present in extrahypothalamic brain and many reproductive tissues. Its cognate receptor was cloned from different vertebrate species, including primates. The human gene homolog of this receptor, however, has a fameshift and stop premature codon, and it appears that GnRH II signaling takes place in humans through the GnRH type I receptor. There is a considerable plasticity in the use of different GnRHs, receptors, and signaling pathways for diverse functions. GnRH and its analogs are used extensively for the treatment of hormone-dependent diseases and in assisted reproductive technology. They are potentially used as contraceptives in men and women. The precise estimation of the molecular mechanisms involved in ligand binding to receptor, subsequent activation, and intracellular signal transduction, is very essential to understanding disease processes. Delineation of the structural elements in GnRH and its receptor, which facilitates differential signaling, will importantly contribute to the development of new interventive analogs. The enormous, broad, multidirectional and profound research on GnRH and its receptor leads, step by step, to an triumphal understanding the kernel of reproductive mechanisms.