Sagawa K, Han B, DuBois D C, Murer H, Almon R R, Morris M E
Department of Pharmaceutics, State University of New York at Buffalo, Amherst, New York, USA.
J Pharmacol Exp Ther. 1999 Sep;290(3):1182-7.
The effects of growth hormone (GH) treatment on renal sodium sulfate cotransport (NaSi-1) were studied in adult (9-10 months) and old (22-23 months) male Fischer 344 rats. All animals received twice-daily s.c. injections of recombinant human GH (hGH; 4 mg/kg) for up to 6 days. Animals were sacrificed by exsanguination on days 0, 1, 2, 3, 4, 5, and 6. Kidneys were removed, and kidney cortex was trimmed immediately and used for RNA and membrane preparations. Plasma hGH concentrations were significantly lower in old rats during the hGH treatment (P <.05). Insulin-like growth factor-I (IGF-I) levels were significantly increased and remained stable after day 2 of hGH treatment in both age groups (P <.05). There was no significant difference in plasma IGF-I levels between age groups. Plasma IGF-I binding protein 3 (IGFBP-3) concentrations were significantly higher in 9- to 10-month-old rats compared with that in 22- to 23-month-old animals (P <.001). There were no significant differences in plasma IGFBP-3 concentrations between days of hGH treatment. The NaSi-1 mRNA levels were significantly lower in 22- to 23-month-old rats compared with that in 9- to 10-month-old animals (P <.001). The NaSi-1 mRNA levels were significantly increased on days 2 and 3 of hGH treatment (P <.05) and then gradually decreased to the control value. The NaSi-1 protein levels in old animals (22-23 months) were also significantly lower than that of 9- to 10-month-old animals and were significantly increased from day 2 of hGH treatment, reaching a maximum level on day 3 or 4 and then returning to the baseline level in both age groups. From these results, it was concluded that 1) NaSi-1 mRNA and protein levels are lower in old animals and increase in both adult and aged rats after hGH treatment, 2) plasma IGF-I levels are similar in adult and aged rats and increase after hGH treatment, and 3) plasma IGFBP-3 levels are lower in old rats and remain unchanged after hGH treatment.
在成年(9 - 10个月)和老年(22 - 23个月)雄性Fischer 344大鼠中研究了生长激素(GH)治疗对肾硫酸根钠共转运体(NaSi - 1)的影响。所有动物每天皮下注射重组人生长激素(hGH;4 mg/kg)两次,持续6天。在第0、1、2、3、4、5和6天通过放血处死动物。取出肾脏,立即修剪肾皮质并用于RNA和膜制备。在hGH治疗期间,老年大鼠的血浆hGH浓度显著较低(P <.05)。在两个年龄组中,hGH治疗第2天后胰岛素样生长因子 - I(IGF - I)水平显著升高并保持稳定(P <.05)。年龄组之间的血浆IGF - I水平无显著差异。与22 - 23个月大的动物相比,9 - 10个月大的大鼠血浆IGF - I结合蛋白3(IGFBP - 3)浓度显著更高(P <.001)。hGH治疗各天之间的血浆IGFBP - 3浓度无显著差异。与9 - 10个月大的动物相比,22 - 23个月大的大鼠中NaSi - 1 mRNA水平显著较低(P <.001)。hGH治疗第2天和第3天NaSi - 1 mRNA水平显著升高(P <.05),然后逐渐降至对照值。老年动物(22 - 23个月)中的NaSi - 1蛋白水平也显著低于9 - 10个月大的动物,并且从hGH治疗第2天开始显著升高,在第3天或第4天达到最高水平,然后在两个年龄组中均恢复到基线水平。从这些结果得出结论:1)老年动物中NaSi - 1 mRNA和蛋白水平较低,hGH治疗后成年和老年大鼠中均升高;2)成年和老年大鼠的血浆IGF - I水平相似,hGH治疗后升高;3)老年大鼠的血浆IGFBP - 3水平较低,hGH治疗后保持不变。