Growth hormone (GH) stimulates insulin-like growth factor-I (IGF-I) and IGF-I-binding protein-3, but not GH receptor gene expression in livers of juvenile rats

Horacio Domené, Kamakshi Krishnamurthi, Rina Eshet, Irit Gilad, Zvi Laron, Izhak Koch, Bethel Stannard, Fernando Cassorla, Charles T. Roberts, Derek LeRoith

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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 μg/kg·day) for 7 days. Sham-operated rats received the same treatment. Hx animals also received T4 (20 μg/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. These findings suggest that in juvenile rats, the IGF-I, IGFBP-3, and GH receptor/GH-binding protein genes are differentially sensitive to GH. Whereas IGF-I gene expression is extremely sensitive to changes in circulating GH levels, IGFBP-3 mRNA appears to be less sensitive to GH, and GH receptor/GH-binding protein mRNA levels appear to be GH independent.

Original languageEnglish (US)
Pages (from-to)675-682
Number of pages8
Issue number2
StatePublished - Aug 1993
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology


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