[Role of testosterone propionate and insulin in the regeneration and growth of bone].
In order to clarify the effects of androgens and insulin (Ins) on the growth and regeneration of bone in growing rats, and to examine the interaction of the two hormones on the bone growth and regeneration, I carried out both in vivo and in vitro experiments using male rats and clonal osteoblastic cells, respectively. In vivo: 1) Three week-old male rats were castrated, and one week after the castration two holes were drilled into their calvariae, followed by subcutaneous administration of 2 mg/kg of testosterone propionate (TP) and/or 20 mg/kg of cyproterone acetate (CPA). After the daily administration of the drugs for two weeks, the calvariae containing wound holes were isolated, and a soft X-ray photograph was taken. The area of the hole in the X-ray film was measured. The calcium (Ca) and the hydroxyproline (HP) contents and alkaline phosphatase (ALPase) activity in the wound and non-wound portions of the calvariae were also determined. 2) Streptozotocin (STZ, 80 mg/kg) was administered intravenously to immature male rats (25-day-old); and three days after the administration, wound holes were made in their calvariae. Ins (10 units/kg) and/or TP (2 mg/kg) were/was administered daily for two weeks starting two weeks after the operation. The length and weight of the femur, and the area of the hole of the calvariae seen in a soft X-ray photograph were measured. The Ca and HP contents in the wound portion, and serum Ca and phosphate (P) levels and ALPase activity were also determined. In vitro: Mouse clonal osteoblastic cells (MC3T3-E1) were incubated in alpha-MEM mudium containing 10% FBS or 0.1% BSA with or without 10(-9)-10(-6) M TP and/or 10(-9)-10(-6) M Ins, the number of cells was counted, and [3H] thymidine incorporation into the cells was assayed for assessment of DNA synthesis. ALPase activity of the cells was also assayed. The results obtained were as follows: 1. The reduction in the wound-hole area was significantly delayed after the castration and was accelerated by TP. This effect of TP was inhibited about 60% by the simultaneous administration of CPA, though this inhibition was not statistically significant. 2. The reduction in HP content of the wound portion by castration was inhibited by TP, and this effect was antagonized by CPA.(ABSTRACT TRUNCATED AT 400 WORDS)
Nishimura
S
S
Department of Dental Pharmacology, Meikai University School of Dentistry, Saitama, Japan.
D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002369:Castration; D002460:Cell Line; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D004247:DNA / Q000096:biosynthesis; D005269:Femur; D006909:Hydroxyproline / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012886:Skull; D013311:Streptozocin / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology*; D014945:Wound Healing
D007328:Insulin; D013739:Testosterone; D017373:Cyproterone Acetate; D013311:Streptozocin; D004247:DNA; D003534:Cyproterone; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium