Abstract
Mutation of a critical carboxy-terminal cysteine residue (C105V) in the thyrotropin-beta (TSH-beta) subunit gene was found in two related families with central hypothyroidism. Affected patients had low thyroid hormone levels and radioactive iodine uptake in the thyroid gland associated with measurable serum TSH. Thyrotropin-releasing hormone-stimulated TSH secretion did not increase thyroid hormone production in these patients as compared to their unaffected siblings, suggesting that the mutant TSH was biologically inactive in vivo. Recombinant TSH harboring this mutation was confirmed to be biologically inactive in an in vitro bioassay. Based on crystallographic structure of chorionic gonadotropin, a disulfide bond between C19 and C105 in the TSH-beta subunit is predicted to form the "buckle" of a "seat belt" that surrounds the common alpha subunit and maintains the conformation and bioactivity of the hormone. This natural mutation of the TSH-beta subunit confirms the importance of the seat belt in the family of pituitary and placental glycoprotein hormones.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
