The proposal addresses the observation that serum osteocalcin is decreased in children with thyroid hormone deficiency. Hypothyroidism produces marked retardation of growth and skeletal maturation in animals and humans. The proposal is designed specifically to evaluate the hypothesis that osteocalcin synthesis is regulated by thyroid hormone and to determine at what intracellular level this regulation takes place. These studies will also provide information concerning the possible utility of serum osteocalcin as a clinical marker of bone growth and maturation. In vivo studies using a rat model will correlate serum osteocalcin levels and bone osteocalcin mRNA levels with parameters of growth, i.e. length and weight and rates of growth during the development of and recovery from propylthiouracil induced hypothyroidism. In vitro studies using a newborn calvariae bone organ culture system will evaluate the direct effect of thyroid hormone on the transcription and translation of osteocalcin mRNA. A rat bone cDNA library will be constructed in lambda GT11 phage and osteocalcin clones will be selected using affinity purified antiosteocalcin antisera. Clones will be characterized for use in the dot blot mRNA determinations.
