title: A potential novel mechanism for precocious puberty in juvenile hypothyroidism.
abstract: Some children with juvenile hypothyroidism exhibit unexplained precocious puberty. Interaction of TSH with the human FSH receptor (hFSH-R) is a possible pathophysiological mechanism for this syndrome that has not been explored due to the lack of hFSH-free TSH preparations and the scarcity of a suitable hFSH-R-based assay system. To devise an in vitro FSH bioassay suitable for exploring this mechanism, we expressed hFSH-R complementary DNA in COS-7 cells and stimulated them with recombinant hTSH (rec-hTSH). Rec-hTSH elicited a dose-dependent cAMP response in the in vitro hFSH-R bioassay; however, the concentration of rec-hTSH required for half-maximal stimulation was several logs greater than that of hFSH. Rec-hTSH acted as a competitive inhibitor of hFSH at the hFSH-R, indicating that hTSH and hFSH are acting through the same receptor, namely the hFSH-R. This provides a potential novel mechanism for the precocious puberty of juvenile hypothyroidism.
authors: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
authors: J N
authors: JN
authors: Anasti
authors: M R
authors: MR
authors: Flack
authors: J
authors: J
authors: Froehlich
authors: L M
authors: LM
authors: Nelson
authors: B C
authors: BC
authors: Nisula
mesh_terms: D001681:Biological Assay; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D007037:Hypothyroidism / Q000150:complications*; D011629:Puberty, Precocious / Q000209:etiology*; D011962:Receptors, FSH / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins; D013972:Thyrotropin / Q000494:pharmacology*; D014162:Transfection
chemical_list: D011962:Receptors, FSH; D011994:Recombinant Proteins; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D000242:Cyclic AMP