title: Transient hypothyroxinemia in juvenile glycoprotein hormone subunit B5 knock-out mice.
abstract: The heterodimer thyrostimulin, comprised of two novel glycoprotein hormone subunits GPA2 and GPB5, activates the TSH receptor. To understand its role in the regulation of the hypothalamus-pituitary-thyroid (HPT-) axis, we evaluated juvenile and adult GPB5 knock-out (GPB5(-/-)) and wild type mice (WT) during euthyroidism, hypothyroidism and thyrotoxicosis. Surprisingly, juvenile euthyroid GPB5(-/-) mice displayed marked hypothyroxinemia (25% lower serum T(4), unchanged TSH) and also during thyrotoxicosis juvenile GPB5(-/-) mice had 25% lower serum T(4), compared to WT. During hypothyroidism, despite similar serum T(4), pituitary TSHbeta mRNA was 2-fold lower in GPB5(-/-) mice compared to WT. Adult mice displayed increased pituitary deiodinase type 2 during euthyroidism and decreased serum T(4) during hypothyroidism in GPB5(-/-). Thus, lacking GPB5 results in moderate deviations of the HPT-axis. The more pronounced differences observed in juvenile mice compared to adult mice are in agreement with the notion that GPB5 has a role during development.
authors.affiliation: Department of Endocrinology & Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.j.vanzeijl@amc.uva.nl
authors.forename: Clementine J J
authors.initials: CJ
authors.lastname: van Zeijl
authors.forename: Olga V
authors.initials: OV
authors.lastname: Surovtseva
authors.forename: Wilmar M
authors.initials: WM
authors.lastname: Wiersinga
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
mesh_terms: D000818:Animals; D001835:Body Weight; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007037:Hypothyroidism / Q000235:genetics / Q000503:physiopathology*; D007605:Juvenile Hormones / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013972:Thyrotropin / Q000097:blood
chemical_list: D006023:Glycoproteins; D007605:Juvenile Hormones; D012333:RNA, Messenger; C458339:thyrostimulin; D013972:Thyrotropin