Distinct mechanisms of cAMP induction by constitutively activating LH receptor and wild-type LH receptor activated by hCG.
Asp578Gly is the major mutation of luteinizing hormone (LH) receptors in humans. It is a dominant mutant, constitutively activates Galphas, and induces cAMP production in the absence of the cognate hormone, causing the familial male precocious puberty. The mechanism of the elevated basal cAMP level is unclear. Our data show strikingly different mechanisms between the elevated basal cAMP induced by the activating mutant and the cAMP induced by the wild-type receptor activated by human chorionic gonadotropin (hCG) binding. The study suggests an approach to attenuating the elevated basal cAMP of the activating mutant LH receptor, which could be useful for controlling the familial male precocious puberty. For the study, we used the C-terminal peptides of Galphas and Galphai2, which couple to the receptor.
Lee
ChangWoo
C
Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
Ji
Inhae
I
Ji
Tae H
TH
D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D044385:GTP-Binding Protein alpha Subunits / Q000737:chemistry / Q000235:genetics; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D017354:Point Mutation; D011629:Puberty, Precocious / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D006063:Chorionic Gonadotropin; D044385:GTP-Binding Protein alpha Subunits; D011974:Receptors, LH; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go