Anabolic Effect of Human Synthetic Parathyroid Hormone-(1-34) Depends on Growth Hormone*

Abstract

We tested whether GH is required for the anabolic effect of PTH on bone, using sham-operated (sham) and hypophysectomized (HX) young male rats. HX rats were supplemented daily with 3% sucrose water, T4, and corticosterone. Rats received vehicle or human PTH-(1-34) at 8 micrograms/100 g, sc, once daily, alone or in combination with rat or ovine GH at 0.2 mg/100 g, sc, twice daily or 12 micrograms ovine GH/100 g.day by continuous sc infusion. After 12 days, rats were sedated, and blood, femurs, and tibias were removed. Femur trabecular and cortical bone calcium (Ca), dry weight (DW), and hydroxyproline were measured. PTH increased bone Ca, DW, and hydroxyproline in shams by approximately 30%, but consistently failed to induce an anabolic response in HX rats. GH alone stimulated systemic growth in HX rats and increased their bone Ca and DW by 2-fold. The anabolic effect of PTH was restored in HX rats given both PTH and GH. Total bone mass in these rats was approximately 20% more (P less than 0.05) than the bone mass of rats given GH alone. When food was restricted in shams to limit systemic growth, PTH still induced an increase in bone mass. We conclude that GH or GH-dependent factors, such as insulin-like growth factor-I, which increases in PTH-treated bones in vitro, are required for the anabolic response of bone to PTH in vivo.