Ossification of the femur in thyroxine-treated tadpoles of Rana pipiens.

Bone is an exclusively vertebrate tissue (McLean and Urist, 1955; Urist, 1964; Johnson, 1966) that develops in teleosts and higher vertebrates during the “metamorphic” period (Witschi, 1956) following larval differentiation of connective tissue and cartilage, Both the thyroid and parathyroid glands are intimately related to differentiation and remodeling of bone (Gorbman and Bern, 1962; AsboeHansen, 1963; Young, 1964; Tapp, 1966; Hamburgh, 1968), but precisely how their hormones influence osseous tissue is unknown. How these hormones regulate calcium mobilization and storage in the skeleton (McLean, 1958; Bassett, 1963; Bronner, 1964) is a fundamental aspect of vertebrate morphogenesis. Extirpation of the thyroid primordium in anuran embryos at the tailbud stage results in excessive larval growth and the arrest of metamorphic changes in the bones of vertebrae and hind limbs (Allen, 1918, 1925; Terry, 1918). Skeletal differentiation resumes in thyroidectomized tadpoles fed thyroid powder (Terry, 1918). Administration of thiourea or thiouracil to larval amphibians mimics thyroidectomy in blocking metamorphosis (Gordon et al., 1945; Steinmetz, 1954). Prolactin likewise is antagonistic to the mechanism by which thyroid hormones stimulate metamorphosis (Etkin and Gona, 1967; Gona, 1967; Brown and Frye, 1969). Amphibian larvae immersed in solutions of thyroxine (Fox and Irving, 1950; Kaltenbach, 1953; Kuhn and Hammer, 1956; Kollros, 1961) or receiving implants of thyroxine mixed with cholesterol or agar (Kaltenbach, 1953; Kuhn and Hammer, 1956) undergo accelerated differentiation of bones of the skull, vertebral column, and limbs. Thyroxine and triiodothyronine promote maturative changes,