The effect of epidermal growth factor on circulating levels of IGF and IGF-binding proteins in adult Goettingen minipigs

Abstract

It has recently been demonstrated that epidermal growth factor (EGF) administration to neonatal rodents causes growth retardation with concomitant reductions in circulation levels of IGF-I. We describe the effects of systemic EGF administration for 4 weeks on circulating levels of IGF-I and IGF-binding proteins (IGFBPs) and on thyroid hormones (tri-iodothyronine, T3; thyroxine, T4) in sexually mature pigs. Goettingen minipigs of either sex were treated with placebo (n = 5) or EGF (30 micrograms/kg per day, n = 6) s.c. for 4 weeks (in relation to an oesophageal sclerotherapy regimen). Blood samples were taken under anaesthesia before and after 1, 2, 3 and 4 weeks of treatment. Circulating levels of IGF-I, insulin, glucose, T3 and T4 were analysed every week and IGFBPs every second week. IGF-I was not reduced significantly after 1 week but significantly reduced after 2 and 3 weeks of EGF treatment. A similar decline was observed for the major IGFBP, IGFBP-3, which was reduced after 2 and 4 weeks. IGFBP-1, IGFBP-2 and IGFBP-4 increased throughout the treatment period (all significantly at week 4). EGF treatment induced increased circulating T3 after 2, 3 and 4 weeks of EGF treatment. In conclusion, we report that EGF treatment for 4 weeks in Goettingen minipigs reduces circulating IGF-I and IGFBP-3, increases circulating IGFBP-1, IGFBP-2 and IGFBP-4, and induces a slight hyperthyroidism as judged from increased circulating levels of T3.

Relationships between Pork Quality Traits and Growth Factor Concentrations in Serum and Longissimus dorsi Muscle before and at Slaughter in Female Market Pigs

“…Interestingly, the well known anti-mitogenic action of TGF-β in myogenic and other types of cells in vitro is believed to be mediated in part by TGF-β-induced IGF-binding protein (IGFBP)-3, which inhibits IGF action (Oh, et al, 1995;Kamanga-Sollo et al, 2003). Similarly, EGF seems to suppress growth in vivo by regulating the expression of IGFBPs (Murray et al, 1993;Vinter-Jensen et al, 1996;Chan and Wong, 2000). Taken together, these reports suggest that systemic and/or local availabilities of IGF-I, TGF-β, and EGF may influence the postmortem muscle quality, which was the basis of the hypothesis of the present study.…”

Heparin-binding EGF-like growth factor (HB-EGF) overexpression in transgenic mice downregulates insulin-like growth factor binding protein (IGFBP)-3 and -4 mRNA

“…As discussed, downregulation of IGFBPs can occur at the transcriptional level or at the post-translational level (Vinter-Jensen et al 1996, Edmondson et al 1999, van Neck et al 2000, Ozawa et al 2004. Our data demonstrating reduced IGFBP-3 and -4 mRNA levels support a transcriptional regulatory mechanism.…”

“…Several in vivo studies have demonstrated the effects of EGF on IGFBPs. For example, a four-week treatment of Goettingen minipigs with EGF resulted in reduced serum IGFBP-3 and IGF-I, while circulating IGFBP-1, -2 and -4 were elevated (Vinter-Jensen et al 1996). Similarly, EGF treatment of neonatal rats resulted in elevated serum IGFBP-1 and -2 without altered IGFBP-3 or -4 levels (Murray et al 1993).…”

Systemic Administration of Epidermal Growth Factor Reduces Fat Mass in Rats: Effects on the Hormone-Sensitive-Lipase, Lipoprotein Lipase and Leptin

“…Due to the lack of plasma we were not able to measure thyroid hormones and catecholamines. However, previous studies have reported increased levels of circulating thyroid hormones in Göttingen minipigs [8]as well as in rats [Flyvbjerg and Vinter-Jensen, unpublished data] treated for 1–4 weeks with subcutaneously administered EGF. The effect in rats is most likely a stimulation of the pituitary as the circulating levels of thyroid-stimulating hormone increases.…”

“…When EGF is systemically administered it may bind to and activate the EGFr, which is also expressed in adipose tissue [5]. On systemic administration EGF may also influence other hormonal systems, thereby exerting indirect effects on adipose tissue [8]. …”