Intravenous infusion of insulin-like growth factor-i (igf-i) in
fetal sheep reduces hepatic igf-i and -ii mrnas.
Kind, Karen L., Julie A. Owens, Fong Lok, Jeffrey S. Robinson, Kirsty
J. Quinn, Linda Mundy, R. Stewart Gilmour, and Phillip C. Owens.
Department of Obstetrics and Gynaecology, University of Adelaide,
Adelaide, South Australia 5005, Cooperative Research Centre for
Tissue Growth and Repair, PO Box 10065, Gouger Street, Adelaide, SA
5000, CSIRO Division of Human Nutrition, PO Box 10041, Gouger Street,
Adelaide, SA 5000, and Department of Cellular Physiology, AFRC
Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom
APStracts 3:0217R, 1996.
Liver contains the highest concentrations of IGF-I mRNA in adult rats
and sheep and is a major source of circulating IGF-I. In rats,
inhibition of hepatic IGF-I production by exogenous IGF-I has been
reported. In fetal sheep, skeletal muscle and liver are major sites
of IGF-I synthesis and potential sources of circulating IGF-I. To
determine if feedback inhibition of IGF gene expression in fetal
liver or muscle by IGF-I occurs, IGF-I and -II mRNAs were measured in
these tissues following intravenous infusion of recombinant human
IGF-I into fetal sheep. Infusion of IGF-I (n=6) (26 +/- 4 [mu]g/h/kg)
or saline (n=6) commenced on day 120 of pregnancy (term= 150 days)
and continued for ten days. Plasma concentrations of IGF-I were
three-fold higher in infused fetuses at 130 days gestation
(P<0.0003), while those of IGF-II were unchanged. IGF-I infusion
reduced the relative abundance of IGF-I mRNA (P<0.0002) and IGF
-II mRNA (P<0.01) in fetal liver by approximately 50%, but did
not alter IGF-I or -II mRNA in skeletal muscle. These results
indicate that IGF-I inhibits the expression of both IGF-I and -II
genes in fetal liver and that IGF gene expression in fetal liver and
muscle are differentially regulated by IGF-I.
Received 13 July 1995; accepted in final form 20 May 1996.
APS Manuscript Number R437-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96