Insulin-like growth factor I (IGF-I) in a growth-enhanced transgenic (GH-overexpressing) bony fish, the tilapia (Oreochromis niloticus): indication for a higher impact of autocrine/paracrine than of endocrine IGF-I

Abstract

Several lines of growth hormone (GH)-overexpressing fish have been produced and analysed for growth and fertility parameters. However, only few data are available on the growth-promoting hormone insulin-like growth factor I (IGF-I) that mediates most effects of GH, and these are contradictory. Using quantitative real-time RT-PCR, radioimmunoassay, in situ hybridization, immunohistochemistry, and radiochromatography we investigated IGF-I and IGF binding proteins (IGFBPs) in an adult (17 months old) transgenic (GH-overexpressing) tilapia (Oreochromis niloticus). The transgenics showed an around 1.5-fold increase in length and an approximately 2.3-fold higher weight than the non-transgenics. Using radioimmunoassay, the serum IGF-I levels were lower (6.22 +/- 0.75 ng/ml) in transgenic than in wild-type (15.01 +/- 1.49 ng/ml) individuals (P = 0.0012). Radioimmunoassayable IGF-I in transgenic liver was 4.2-times higher than in wild-type (16.0 +/- 2.21 vs. 3.83 +/- 0.71 ng/g, P = 0.0017). No hepatocytes in wild-type but numerous hepatocytes in transgenic liver contained IGF-I-immunoreactivity. RT-PCR revealed a 1.4-times higher IGF-I mRNA expression in the liver of the transgenics (10.51 +/- 0.82 vs. 7.3 +/- 0.49 pg/microg total RNA, P = 0.0032). In correspondence, in situ hybridization showed more IGF-I mRNA containing hepatocytes in the transgenics. A twofold elevated IGF-I mRNA expression was determined in the skeletal muscle of transgenics (0.33 +/- 0.02 vs. 0.16 +/- 0.01 pg/microg total RNA, P < 0.0001). Both liver and serum of transgenics showed increased IGF-I binding. The increased IGFBP content in the liver may lead to retention of IGF-I, and/or the release of IGF-I into the circulation may be slower resulting in accumulation of IGF-I in the hepatocytes. Our results indicate that the enhanced growth of the transgenics likely is due to enhanced autocrine/paracrine action of IGF-I in extrahepatic sites, as shown here for skeletal muscle.

Regulation of endocrine and paracrine sources of Igfs and Gh receptor during compensatory growth in hybrid striped bass (Morone chrysops×Morone saxatilis)

“…In particular, transgenic tilapia overexpressing Ghs were twofold heavier than wild types yet had depressed levels of plasma Igf1 and elevated skeletal muscle igf1 gene expression (Eppler et al 2007). This raises the possibility that autocrine/paracrine sources of Igf1 may be a significant contributor to somatic growth.…”

“…In addition to hepatic binding, GH may also act directly on target tissues such as skeletal muscle to stimulate the production of IGF1, which in turn can act in a paracrine/autocrine fashion to stimulate tissue growth (Chauvigné et al 2003). The potential contribution of locally produced Igf1 to anabolism is further underscored by studies in Gh-transgenic tilapia (Oreochromis niloticus), which showed elevated growth and skeletal igf1 mRNA but reduced plasma Igf1 relative to wild-type controls (Eppler et al 2007). Unlike postnatal mammals, circulating as well as locally produced Igf2 may also have mitogenic effects in adult fishes (Chen et al 2000, Peterson et al 2004, Terova et al 2007).…”

Effects of short-term growth hormone treatment on liver and muscle transcriptomes in rainbow trout (Oncorhynchus mykiss)

“…This may suggest a common effect of either GH or IGF-I in the extrahepatic sites. In a GH transgenic tilapia, Eppler et al (16) reported common extrahepatic modulation of gene expression.…”

Dynamic transcriptional regulation of autocrine/paracrine igfbp1, 2, 3, 4, 5, and 6 in the skeletal muscle of the fine flounder during different nutritional statuses

“…In particular, muscle-derived IGF1 has been proposed as the main regulator of growth in mammals (Sjögren et al 1999, Yakar et al 1999. As in mammals, some recent evidence has shown that in fish, local Igf1 is of importance in muscle growth (Eppler et al 2007, Fox et al 2010, Fuentes et al 2012a. The dynamic of the biological actions of IGFs is modulated by the binding of these growth factors with either specific membrane receptors and/or the IGFBPs.…”