Effect of growth hormone and pamidronate on bone blood flow, bone mineral and IGF-I levels in the rat.
So far it is not known whether the growth hormone (GH) has an effect on the local blood circulation in bones. Using male rats we studied the local blood circulation in the tibia and the distal end of the femur (by means of the uptake of 85Sr-microspheres), the density and ash weight of the tibia, the urinary excretion of pyridinoline (PD) and deoxypyridinoline (DPD) as an indicator of bone resorption and the blood levels of IGF-I after the administration of human GH (4 mg/kg s.c. daily for 4 weeks) and/or bisphosphonate pamidronate (Aredia, CIBA-Geigy, administered in the dose of 3 mg/kg i.p. on day 1, 2, 9 and 10). The rats were divided into four groups: 1. controls, 2. GH, 3. pamidronate, 4. GH plus pamidronate. After the administration of GH, we observed a significant increase in bone blood flow (and in the uptake of 85Sr-microspheres), a decrease in the density and ash weight of the tibia and increased urinary excretion of PD and DPD; IGF-I levels in the blood were non-significantly elevated. Simultaneously administered pamidronate inhibited all significant effects of GH and it also decreased the IGF-I levels in rats treated with GH. After the administration of pamidronate itself the bone density and ash weight of the tibia were increased and urinary DPD excretion was decreased. In view of the known vascular effects of IGF-I, we assume that the increase in bone blood flow after the administration of GH and its reduction after simultaneous administration of pamidronate could be mediated by the changes of IGF-I blood levels, although the effect of pamidronate on IGF-I is still not clear. Regarding the role of blood circulation in rat bones, we consider that our present results are further evidence for the relationship between the blood circulation in bones and bone resorption, although these results do not show how active is bone blood circulation in the regulation of bone tissue metabolism.
Kapitola
J
J
Laboratory for Endocrinology and Metabolism, Charles University, Prague, Czech Republic.
Zák
J
J
Lacinová
Z
Z
Justová
V
V
D000596:Amino Acids / Q000652:urine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism; D001842:Bone and Bones / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008863:Microspheres; D000077268:Pamidronate; D051381:Rats
D000596:Amino Acids; D004164:Diphosphonates; C015484:pyridinoline; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C036020:deoxypyridinoline; D000077268:Pamidronate