A factor that lowers serum calcium and inorganic phosphate in rats has been purified 500-fold from 0.1N HCl extracts of hog thyroid glands. It is distinct from thyroxine and triiodothyronine and appears to be a polypeptide.

Human a and /3 transforming growth factors (TGF-a and TGF-/8) stimulated the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvaria in organ culture. Significant stimulation of bone resorption by TGF-a was observed with a concentration of 0.2 ng/ml (35 pM) and by TGF-.6 with 0.2 ng/ml (8.0 pM).Enhanced production of PGE2 and bone resorption stimulated by either TGF-a or TGF-.8 were both inhibited by indomethacin. We conclude that TGF-a and TGF-.8 are potent and powerful stimulators of the resorption of mouse bone by a mechanism that involves the enhanced local production of PGE2.

Goldhaber has described a transplantable mouse fibrosarcoma which enhances the resorption of bone in tissue culture (2, 3). When fragments of the tumor (HSDM1) were placed in the same culture vessel with mouse calvaria, marked resorption of the bone was observed. Fragments of HSDM1 tumor could be cultured alone, and the medium from such explants also s t i m u l a t e d bone resorption when it was added to calvaria in organ culture. These findings suggested that the tumor was synthesizing and secreting a bone resorption-stimulating factor. Results of our previous experiments revealed that the factor could be extracted from the tumor tissue and recovered from the medium of HSDM1 cells grown in monolayer culture (1). Of particular interest was the finding that the HSDM1 factor could be extracted into organic solvents, and that it had several chemical and biological properties of a prostaglandin.We have recently reported that HSDM1 cells in culture synthesize and secrete large amounts of prostaglandin E2 (4). In the present report, we wish to present evidence that leads us to conclude that the bone resorption-stimulating factor produced b y the HSDM1 tumor is prostaglandin Ee. Materials and MethodsThe HSDM1 Tumor.--A fibrosarcoma was induced in a Swiss albino mouse by subcutaneous implantation of a Millipore filter (5, 6). The tumor has been passed serially in mice of the same strain for more than a decade. Excised tumor from a donor mouse is minced into

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