Intramammary infusion of Panax ginseng extract in the bovine mammary gland at cessation of milking modifies components of the insulin-like growth factor system during involution.

The objective of this study was to evaluate the effects of a single intramammary infusion of Panax ginseng extract (GS) on insulin-like growth factors (IGF) in bovine mammary gland during early involution. Eight mammary quarters from six nonpregnant cows in late lactation were infused with 10 mL of ginseng extract solution (3 mg/mL), six quarters were treated with 10 mL of placebo (vehicle alone) and six quarters were maintained as uninoculated controls. Milking was interrupted after infusion. Concentrations of IGF1 in mammary secretions were higher in GS-treated quarters than in placebo and uninoculated control quarters at 24, 48 and 72 h post-treatment (p<0.05). Treatment with GS did not affect mammary secretion of IGF2 (p=0.942). At 7 d of post-lactational involution, a decrease of immunostained area and mRNA expression for IGF1 was observed in mammary tissue of GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). The IGF2 immunostained area and mRNA expression for this growth factor were not affected by GS treatment (p=0.216 and p=0.785, respectively). An increase in protein levels and mRNA expression in mammary tissue of IGFBP3, IGFBP4 and IGFBP5 was observed in GS-treated quarters compared with placebo-treated quarters and uninoculated controls (p<0.05). These results provide evidence that intramammary inoculation of GS extract at cessation of milking may promote early mammary involution through the inhibition of IGF1 local production and bioavailability.

Reduction in atherosclerotic lesion size in pigs by alphaVbeta3 inhibitors is associated with inhibition of insulin-like growth factor-I-mediated signaling.

Insulin-like growth factor-I (IGF-I) is a potent stimulant of smooth muscle cell (SMC) migration and proliferation and has been implicated in the development of experimental atherosclerotic lesions. Because optimal stimulation of SMC in vitro by IGF-I requires ligand occupancy of alphaVbeta3, these studies were conducted to determine whether alphaVbeta3 antagonists would result in a change in lesion size and whether they could alter IGF-I-mediated actions. Clamps were placed on the carotid and femoral arteries of normal pigs that had been fed a high-cholesterol diet for 4 weeks. alphaVbeta3 inhibitors (SC-69000, SC-65811) (10(-6) mol/L) or saline were infused for 2 weeks into the peristenotic area. Lesion area, the number of SMC layers, and proliferating cell nuclear antigen positive cells were determined in a 1.2-mm segment of each artery. Lesion areas were 304 788+/-113 453 micron(2) (saline), compared with 149 799+/-35 456 micron(2) (SC-69000) (P<0.01). Lesion areas in arteries treated with SC-64258, a compound that does not bind to alphaVbeta3, were 310 284+/-160 467 micron(2), P=not significant. In a second experiment, lesion areas were 110 391+/-17 347 micron(2) (saline) and 59 533+/-17 568 micron(2) (SC-65811, P<0.001). Neointimal SMC layers were reduced by SC-65811 from 7.4+/-4.5 to 3.0+/-0.4 (P<0.001). To determine whether IGF-I action was altered, IGF binding protein-5, which is synthesized in response to IGF-I, was analyzed. IGF-I binding protein-5 mRNA abundance was reduced by 67+/-8% in the 6 lesions treated with SRL-69000 compared with saline controls (P<0.001). We conclude that alphaVbeta3 antagonists block the development of lesions in pigs that have been induced by a high-cholesterol diet and stenosis, and the effect of these compounds is associated with their ability to inhibit IGF-I-mediated signaling.

Molecular cloning and sequence analysis of the porcine insulin-like growth factor binding protein-5 complementary deoxyribonucleic acid.

We report here for the first time the isolation of a cDNA clone containing the open reading frame sequence for porcine insulin-like growth factor binding protein-5 (pIGFBP-5) and the complete deduced amino acid sequence for this porcine IGFBP. The cDNA sequence shares 94%, 90% and 91% identity to its human, mouse and rat counterparts, respectively. The deduced amino acid sequence consists of 252 amino acids and a putative 19 amino acid signal and shares 97%, 96%, and 96% identity to the human, mouse and rat peptides, respectively. The mature peptide contains the 18 conserved cysteines found in all of the IGFBPs. Northern blot analysis of total RNA isolated from porcine heart, muscle and spleen using a 315 base pair cDNA insert derived from the pIGFBP-5 open reading frame sequence revealed a single mRNA transcript of 6.0 kilobases.