Domené H, Krishnamurthi K, Eshet R, Gilad I, Laron Z, Koch I, Stannard B, Cassorla F, Roberts C T, LeRoith D
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1993 Aug;133(2):675-82. doi: 10.1210/endo.133.2.7688291.
In the adult rat, expression of the liver GH receptor, insulin-like growth factor-I (IGF-I), and IGF-I-binding protein-3 (IGFBP-3) genes has been shown to be under GH control. Additionally, hypophysectomy and GH treatment have a differential effect on the relative abundance of liver IGF-I mRNA variants in adult rats. To further elucidate the time of appearance and the extent of GH control of liver GH receptor, IGF-I, and IGFBP-3 gene expression, we studied the effect of hypophysectomy and GH and IGF-I treatment in juvenile rats. Male Wistar rats were hypophysectomized (Hx) on postnatal day 26 and received twice daily sc injections of saline, recombinant human GH (2.5 U/kg.day), or recombinant human IGF-I (500 micrograms/kg.day) for 7 days. Sham-operated rats received the same treatment. Hx animals also received T4 (20 micrograms/kg.day). In Hx animals, there was a significant reduction in body weight (69.8 +/- 6.6 vs. 100.4 +/- 5.4 g; P < 0.001). GH, but not IGF-I, treatment increased body weight (79.6 +/- 9.6 g after GH vs. 69.8 +/- 6.6 g before GH; P < 0.05). GH treatment partially maintained liver, kidney, and lung weights in Hx animals and increased them in intact animals, whereas IGF-I treatment did so only in the lungs of intact and Hx animals. Serum GH and IGF-I levels were markedly reduced in Hx animals compared with those in intact controls, and GH treatment maintained, albeit partially, circulating IGF-I levels compared with those in saline-treated Hx animals. IGF-I mRNA levels were markedly reduced in Hx liver (25.0 +/- 5.4%; P < 0.001 compared with intact controls). GH treatment for 7 days increased IGF-I mRNA levels by 4.8-fold over the levels in 9-day Hx animals and increased IGF-I mRNA levels by 2.2-fold in control rats. Hypophysectomy decreased exon 2-containing transcripts by 7.0-fold and exon 1-containing transcripts by 4.1-fold. GH treatment, however, affected both exon 1- and exon 2-containing transcripts similarly. Hepatic IGFBP-3 mRNA levels were reduced in Hx (53.2 +/- 1.8%; P < 0.01 compared with intact controls) and IGF-treated Hx animals, but were not decreased in Hx GH-treated animals (100.6 +/- 9.5). No changes in GH receptor or GH-binding protein mRNA levels were caused by Hx, GH, or IGF-I treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
在成年大鼠中，肝脏生长激素（GH）受体、胰岛素样生长因子-I（IGF-I）和IGF-I结合蛋白-3（IGFBP-3）基因的表达已被证明受GH调控。此外，垂体切除和GH治疗对成年大鼠肝脏IGF-I mRNA变体的相对丰度有不同影响。为了进一步阐明肝脏GH受体、IGF-I和IGFBP-3基因表达出现的时间以及GH调控的程度，我们研究了垂体切除以及GH和IGF-I治疗对幼年大鼠的影响。雄性Wistar大鼠在出生后第26天接受垂体切除（Hx），并每天皮下注射两次生理盐水、重组人生长激素（2.5 U/kg·天）或重组人IGF-I（500微克/kg·天），持续7天。假手术大鼠接受相同治疗。Hx动物还接受甲状腺素（T4，20微克/kg·天）。在Hx动物中，体重显著降低（69.8±6.6克对100.4±5.4克；P<0.001）。GH治疗而非IGF-I治疗增加了体重（GH治疗后为79.6±9.6克，治疗前为69.8±6.6克；P<0.05）。GH治疗部分维持了Hx动物的肝脏、肾脏和肺重量，并增加了完整动物的这些器官重量，而IGF-I治疗仅在完整和Hx动物的肺中起到了这样的作用。与完整对照组相比，Hx动物的血清GH和IGF-I水平显著降低，与生理盐水处理的Hx动物相比，GH治疗虽只是部分维持了循环IGF-I水平。Hx肝脏中的IGF-I mRNA水平显著降低（25.0±5.4%；与完整对照组相比P<0.001）。GH治疗7天使IGF-I mRNA水平比9天Hx动物的水平增加了4.8倍，在对照大鼠中增加了2.2倍。垂体切除使含外显子2的转录本减少了7.0倍，含外显子1的转录本减少了4.1倍。然而，GH治疗对含外显子1和外显子2的转录本的影响相似。肝脏IGFBP-3 mRNA水平在Hx组（53.2±1.8%；与完整对照组相比P<0.01）和IGF治疗的Hx动物中降低，但在Hx+GH治疗的动物中未降低（100.6±9.5）。Hx、GH或IGF-I治疗均未引起GH受体或GH结合蛋白mRNA水平的变化。（摘要截断于400字）
