Pharmacokinetics and bioactivity of intact versus truncated IGF-I during a 24-h infusion into lactating goats.
The aim of this study was to compare the plasma concentration profile, mammary blood flow response and transfer into milk of intact IGF-I with that of its truncated analogue, des(1-3)IGF-I (des-IGF-I). Each peptide was infused for 24 h into the pudic artery supplying one mammary gland of lactating goats (n = 5). Concentrations of IGF-I in plasma (from the jugular vein) rose rapidly during infusion of IGF-I or des-IGF-I to reach 510 +/- 62 and 640 +/- 32 ng/ml (mean +/- S.E.M.) respectively, compared with 262 +/- 35 ng/ml after a similar infusion of saline. Ligand blotting analysis indicated a significant increase in the intensity of [125I]IGF-I binding to the 40-43 kDa doublet (binding protein-3 (BP-3), P < 0.01) and the band at 31 kDa (P < 0.05) during infusion of either IGF-I or des-IGF-I, as compared with saline. Furthermore des-IGF-I induced a significant increase in intensity of binding to the 35 and 24 kDa bands, but IGF-I did not. Whereas [125I]IGF-I was distributed between BP-3 and the other binding proteins, [125I]des-IGF-I bound exclusively to BP-3. Mammary blood flow (MBF) increased 48 +/- 6% after 12 h of infusion of des-IGF-I, compared with an increase of 22 +/- 6% during IGF-I. The difference in response was significant at P < 0.05. In addition, more IGF-I was secreted into the milk of the infused than the non-infused gland during either infusion of IGF-I or des-IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
Prosser
C G
CG
Dairying Research Corporation, Hamilton, New Zealand.
Davis
S R
SR
Hodgkinson
S C
SC
Mohler
M A
MA
D000818:Animals; D005260:Female; D006041:Goats / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000493:pharmacokinetics*; D007774:Lactation / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000098:blood supply / Q000378:metabolism; D010446:Peptide Fragments / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000187:drug effects
D010446:Peptide Fragments; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I