The biology of gonadotropin hormone-releasing hormone: role in the control of tumor growth and progression in humans.

摘要: It is now well known that different forms of GnRH coexist in the same vertebrate species. In humans, two have been identified so far. The first form corresponds to hypophysiotropic decapeptide, and called GnRH-I. second has initially chicken brain, it referred as GnRH-II. GnRH-I binds activates specific receptors, belonging 7 transmembrane (7TM) domain superfamily, present on pituitary gonadotropes. These receptors (type I receptors) are coupled Gq/11/PLC intracellular signalling pathway. A receptor for GnRH-II II receptor) non-mammalian vertebrates primates, but not yet humans. last 10-15 years experimental evidence accumulated indicating expressed, together with its tumors reproductive tract (prostate, breast, ovary, endometrium). these hormone-related tumors, activation type consistently decreases cell proliferation, mainly by interfering mitogenic activity stimulatory growth factors (e.g., EGF, IGF). Recent data seem suggest might also reduce migratory invasive capacity cancer cells, possibly affecting expression and/or adhesion molecules enzymes involved remodelling extracellular matrix. observations point an autocrine negative regulatory factor tumor progression metastatization. Extensive research performed clarify molecular mechanisms underlying peculiar antitumor Type correspond those at level terms cDNA nucleotide sequence protein weight, do share pharmacological profile binding affinity synthetic analogs. Moreover, classical pathway mediating decapeptide gonadotropin synthesis secretion inhibitory growth. Gi-cAMP, rather than Gq/11-PLC, signal transduction Recently, we reported expressed related system, such melanoma. Also melanoma behaves a regulator progression. Interestingly, biochemical profiles level. far possible functions humans still scanty. identified, 'putative' receptor, both central nervous system peripheral structures, tissues (both normal tumoral). biological presently under investigation.