Somatostatin infusion inhibits the stimulatory effect of testosterone on endosteal bone formation in the mouse.
To investigate whether the effects of testosterone (T) on endosteal bone metabolism may be mediated by growth hormone (GH), intact male mice were infused for ten days with T (5 or 15 mg/kg/d) alone, or combined either with native somatostatin (SRIF) (220 micrograms/kg/d) or with the long-acting somatostatin analog SMS 201-995. Testosterone infusion induced a dose-dependent increase in histomorphometric parameters of bone formation, causing a 25% increase in osteoblastic and osteoid surface and 10% to 12% stimulation of the matrix and mineral appositional rates. Stimulation of bone formation rate was associated with a 2- to 3-fold increase in the incidence of serum GH peaks of high amplitude. SRIF (220 micrograms/kg/d) and SMS at low dose (4.32 micrograms/kg/d) decreased parameters of bone formation by 20% to 25%. At a higher dosage (13 micrograms/kg/d), which mildly decreased serum glucose and longitudinal bone growth, SMS further reduced bone formation rate. Infusion of SRIF with T (5 mg/kg/d) blunted the stimulatory effect of T. Similarly, infusion of a high dose of SMS (13 micrograms/kg/d), together with T (15 mg/kg/d), abolished the effect of T (15 mg/kg/d) without altering serum glucose or mineral levels. The effect of SRIF on testosterone-induced (5 mg/kg/d) bone formation was associated with inhibition of T-induced high-amplitude GH peaks. The results indicate that T stimulates the osteoblastic bone formation in association with increased GH secretion, whereas SRIF and the analog SMS produce inhibitory effects.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015282:Octreotide; D010012:Osteogenesis / Q000187:drug effects*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*
D001786:Blood Glucose; D013739:Testosterone; D013004:Somatostatin; D013006:Growth Hormone; D015282:Octreotide