GnRH signaling in intrauterine tissues.
Type I GnRH (GnRH-I, GNRH1) and type II GnRH (GnRH-II, GNRH2), each encoded by separate genes, have been identified in humans. The tissue distribution and functional regulation of GnRH-I and GnRH-II clearly differ despite their comparable cDNA and genomic structures. These hormones exert their effects by binding to cell surface transmembrane G protein coupled receptors and stimulating the Gq/11 subfamily of G proteins. The hypothalamus and pituitary are the main origin and target sites of GnRH, but numerous studies have demonstrated that extra-hypothalamic GnRH and extra-pituitary GnRH receptors exist in different reproductive tissues such as the ovary, endometrium, placenta, and endometrial cancer cells. In addition to endocrine regulation, GnRH is also known to act in an autocrine and paracrine manner to suppress cell proliferation and activate apoptosis in the endometrium and endometrial cancer cells through several mechanisms. Both GnRH-I and GnRH-II exhibit regulatory roles in tissue remodelling during embryo implantation and placentation, which suggests that these hormones may have important roles in embryo implantation and early pregnancy. The presence of varied GnRH and GnRH receptor systems demonstrate their different roles in distinct tissues using dissimilar mechanisms. These may result in the generation of new GnRH analogues used for several hormone-related diseases.
Wu
Hsien-Ming
HM
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia V6H3V5, Canada.
Wang
Hsin-Shih
HS
Huang
Hong-Yuan
HY
Soong
Yung-Kuei
YK
MacCalman
Colin D
CD
Leung
Peter C K
PC
D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D049109:Cell Proliferation; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D019899:Paracrine Communication; D011966:Receptors, LHRH / Q000378:metabolism; D015398:Signal Transduction; D014591:Uterine Diseases / Q000188:drug therapy / Q000378:metabolism; D014599:Uterus / Q000378:metabolism* / Q000473:pathology
D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone