Secretion of a Bone Resorbing Factor by Chick Thyroid Glands in Organ Culture

The ability of the thyroid gland to secrete a bone resorbing factor in vitro was studied using glands obtained from 20-day-old chick embryos. The glands were incubated in a modified BGJ medium containing 1 mg/ml bovine serum albumin under 5% CO2-40% O2 at 37 C. The culture media were assayed in vitro by measuring the stimulation of the release of previously incorporated 45Ca from cultured 19-day fetal rat bone shafts over a 48 h period. The glands secreted a stimulator of bone resorption which did not appear to be parathyroid hormone (PTH). The dose-response curve for the thyroid gland factor was not parallel to that obtained using PTH and secretion was not under calcium control. Neither thyroxine (T4) nor triiodothyronine (T3) produced a marked stimulation of bone resorption over a wide range of doses. Bone resorption stimulated by the thyroid gland factor was inhibited by calcitonin (CT). Concentrations of TH and thyroid gland factor which were minimally effective when tested separately, produced a marked synergistic response when added together. This synergism was not seen when T4, T3, PGE1, or PGE2 were tested with PTH. Media obtained by culturing explants of embryonic chick liver, heart and muscle did not have bone resorbing activity. Secretion of the bone resorbing factor by thyroid glands was blocked by Indomethacin (10(-5)M) but the effects of the factor on bone were not blocked by this agent. These results suggest that the thyroid gland is capable of secreting a stimulator of bone resorption, possibly a prostaglandin, which is capable of synergizing with PTH, and which may represent a tissue factor which under certain circumstances may exert an influence on bone.