Growth hormone and the expression of mRNAs for matrix proteins and oncogenes in bone

To examine the effects of growth hormone (GH) on the expression of the mRNAs of bone matrix proteins, three experiments were carried out with 3-month-old female Sprague-Dawley rats. In the first experiment rats were given a single subcutaneous injection of recombinant human GH (8 mg rhGH/kg b. wt.), sacrificed 15 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h later, and RNA isolated from cancellous bone from the distal femoral metaphysis. Growth hormone increased the level of type I collagen mRNA by 187, 417, and 509% over the control level at 15 min, 1 h and 2 h, respectively; the mRNA levels declined to 119 and 99% at 4 and 8 h, respectively, and then rose again to 351 and 423% over the control level at 16 and 24 h, respectively. Osteocalcin mRNA transcript increased by 89, 90, 325, 342, 361, and 407% over the control level at 15 min, 1 h, 2 h, 4 h, 8 h and 16 h, respectively, and fell to 66% at 24 h. The level of IGF-I mRNA increased by 45, 83, 120, 140, and 175% over the control level at 2, 4, 8, 16, and 24 h, respectively. In the second experiment, following the administration of rhGH (8 mg/kg b. wt.) bone osteocalcin mRNA increased by 127, 177, 361, and 413% over the control level at 30 min, 1 h, 2 h and 4 h, respectively; IGF-I mRNAs increased by 38, 33, 87, and 437 at 30 min, 1 h, 2 h and 4 h, respectively, but the levels did not become significant until 2 h; c-fos mRNA increased significantly at 30 min, and c-jun and c-myc mRNAs did not increase until 4 h. In the third experiment, animals were given a single injection of rhGH (8 mg/kg b. wt.) and the animals were bled at timed intervals and acid ethanol-extractable serum IGF-I determined. Serum IGF-I increased significantly only at 12 h following rhGH administration. Our data indicate that GH stimulates a rapid increase in the expression of mRNAs for the bone matrix proteins, type I collagen and osteocalcin, by a mechanism that appears to be independent of IGF-I, the early response oncogenes or an increase in osteoblast number.