title: Biphasic response of rat tibial growth to thyroxine administration.
abstract: To evaluate the dose-response relationship between thyroxine and tibial growth, 60 male rats age 21 days were rendered hypothyroid by administration of methimazole in the drinking water. Twenty-one days later, the hypothyroid rats were randomly divided into 5 groups which received 0, 2, 8, 32, or 64 micrograms.kg-1.day-1 of T4 im for 21 days. All animals were sacrificed at age 64 days. Rat tibia were removed for measurement of epiphyseal growth plate width and longitudinal growth rate. Serum T4 and IGF-I levels were determined by RIA. Methimazole therapy significantly decreased serum T4, IGF-I, epiphyseal growth plate width, and longitudinal growth rate compared to controls. Epiphyseal growth plate width gradually increased when T4 was administered at doses from 2 to 32 micrograms.kg-1.day-1 (271 +/- 14, 311 +/- 15 and 324 +/- 11 microns), and subsequently decreased when T4 was given at a dose of 64 micrograms.kg-1.day-1 (267 +/- 8 microns). A similar profile was observed for longitudinal growth rate and IGF-I. We conclude that rat tibial growth has a biphasic response to exogenous T4 administration, and that the effects of T4 on tibial growth may be mediated through IGF-I secretion.
authors.affiliation: Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: S G
authors.initials: SG
authors.lastname: Ren
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: D E
authors.initials: DE
authors.lastname: Sweet
authors.forename: S
authors.initials: S
authors.lastname: Malozowski
authors.forename: F
authors.initials: F
authors.lastname: Cassorla
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D006132:Growth Plate / Q000473:pathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008713:Methimazole; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*
chemical_list: D008713:Methimazole; D007334:Insulin-Like Growth Factor I; D013974:Thyroxine