title: Metabolic response of sheep skin to a chronic infusion of a variant of insulin-like growth factor I.
abstract: The effects of a chronic (21-day) skin infusion of a variant of insulin-like growth factor I (IGF-I) (long-Arg3-IGF-I; LR3IGF-I) on short-term (48 h) responses of skin metabolism and 21-day plasma hormone concentration, wool-follicle characteristics and wool production were investigated in well-fed castrated Romney sheep. A bilateral arteriovenous preparation was used to infuse LR3IGF-I continuously into the skin on one abdominal flank and saline into the other abdominal flank of six sheep; a further six sheep had one flank infused with saline (controls). LR3IGF-I caused an initial (4-24 h) reduction in the plasma concentrations of amino acids, especially tyrosine, valine and lysine, and, after 24 h, significant (P < 0.05) reductions in blood oxygen and plasma glucose concentrations. After 4 h of LR3IGF-I infusion, there was a significant increase in blood flow (P < 0.05) and oxygen uptake (P < 0.05), and net uptake of amino acids [which was significant (P < 0.05) for valine and phenylalanine] by the LR3IGF-I-infused skin was increased. Total uptake of phenylalanine for skin protein synthesis, measured using [3H]phenylalanine uptake, was also significantly increased after 4 and 24 h of infusion. After 48 h of infusion all LR3IGF-I-dependent measurements of metabolic parameters had fallen to preinfusion values. By day 7 of the 21-day infusion there was a significant (P < 0.05) decrease in circulating endogenous IGF-I in plasma of treated sheep compared with that of control sheep, followed by a significant (P < 0.05) increase between day 7 and 21. Plasma insulin levels followed a similar pattern. There was no change at any stage of infusion in IGF-binding proteins in the plasma of the two LR3IGF-I-infused sheep tested, and it is concluded that LR3IGF-I caused a down-regulation of the type-I IGF-I receptors followed by a rise in endogenous IGF-I concentration consequent on lack of feedback regulation. After 21 days of infusion there was no effect of LR3IGF-I on wool-follicle-bulb-cell mitotic rate, bulb diameter or wool production.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: New Zealand Pastoral Agriculture Research Institute, Dairy and Beef Division, Palmerston North.
authors.forename: J E
authors.initials: JE
authors.lastname: Hocking Edwards
authors.forename: S K
authors.initials: SK
authors.lastname: Khalaf
authors.forename: B R
authors.initials: BR
authors.lastname: Sinclaire
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: C G
authors.initials: CG
authors.lastname: Prosser
authors.forename: P M
authors.initials: PM
authors.lastname: Harris
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D010100:Oxygen / Q000097:blood; D012756:Sheep; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014935:Wool
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; C084339:LR(3)IGF-I; D007773:Lactates; D007334:Insulin-Like Growth Factor I; D010100:Oxygen