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The role of insulin-like growth factor 1 (IGF-1) in renal growth of obstructed and contralateral kidneys was investigated for 10 days following unilateral ureteric obstruction in male Wistar rats. The weight of the obstructed kidney increased rapidly, rising from 671 +/- 10 to 1,378 +/- 42 mg on day 10, an increase of 105%. IGF-1 content of the obstructed kidney was significantly less than in control kidneys from day 2 onwards, reaching a nadir of 70 ng/mg, a fall of 64%. The protein concentration, expressed as milligrams per gram kidney weight, also fell rapidly from 141 +/- 11 to 88 +/- 3 mg/g on day 6. The weight of the contralateral kidney increased by 32%, from 671 +/- 10 to 887 +/- 48 mg on day 10. The IGF-1 content of this kidney was increased by 48% from baseline on day 1 (268 +/- 23 vs. 191 +/- 13 ng/g) and remained increased compared to sham-operated animals on days 6 and 8. The protein content, expressed as milligrams per gram kidney weight, remained constant throughout the study. We conclude that in the acutely obstructed left kidney increasing kidney weight is associated with falling concentration of IGF-1 and protein and may be due to oedematous and reactive change. Growth of the contralateral kidney is preceded by a rise in the concentration of IGF-1 and may represent true renal compensatory growth.

We have treated two groups of infertile men with growth hormone (GH), namely nine oligozoospermic (< 5 x 10(6) sperm/mL) males and nine asthenozoospermic (percentage mobile sperm < 30 and > 15 x 10(6) sperm/mL) males. The patient groups had a significantly lower GH response to an arginine GH stimulation test as compared to a control group. Each patient was treated with GH for 12 weeks and followed for a total of 36 weeks with sampling of blood and semen. Sperm motility increased significantly during GH treatment in both patient groups. There was no difference in sperm count during the treatment. There were three pregnancies in the nine couples from the asthenozoospermic group and no pregnancies in the oligozoospermic group. Furthermore, we found that seminal plasma IGF-I increased simultaneously with the increase in sperm motility. These data suggest that GH stimulates IGF-I production from Sertoli and/or Leydig cells, which in a paracrine/autocrine manner stimulates maturation of spermatozoa with subsequent increased sperm motility.

Angiopeptin, a somatostatin analogue, inhibits intimal hyperplasia after (percutaneous transluminal coronary angioplasty) (PTCA) in several animal models. This pilot study sought to determine the effect of subcutaneous infusion of angiopeptin on clinical events and restenosis in patients undergoing successful PTCA. One hundred and twelve patients were randomized to receive continuous subcutaneous angiopeptin (750 micrograms/day) or placebo infusion from the day before PTCA and for the following four days in a double-blind study. Eighty patients had a successful PTCA, and 75 of these patients with 94 lesions underwent angiography 6 +/- 2 months after PTCA. All 112 patients underwent clinical follow-up at 12 months. The 12-month event rate (death, myocardial infarction, coronary artery bypass grafting and re-PTCA) was reduced from 34% to 25% (p = 0.30) by angiopeptin by intention to treat analysis. Restenosis (or = 50% diameter stenosis) was significantly reduced in lesions treated with angiopeptin (12% vs 40%; p = 0.003). Late lumen loss was also significantly reduced after angiopeptin treatment (0.12 +/- 0.46 mm vs 0.52 +/- 0.64 mm; p = 0.003). In conclusion, continuous subcutaneous angiopeptin infusion for five days tended to decrease clinical events and restenosis after PTCA.

If GH and IGF-I are involved in early and probably long-term renal changes following kidney ablation, and therefore theoretically also in the series of events after a kidney transplantation, the effect of somatostatin analogue should be investigated further. Pronounced effects have been observed in a small number of reports in unilateral nephrectomy and experimental diabetes models, but until now no trials have been published on kidney transplantation models. In contrast, studies have already been performed on somatostatin analogues' effects on vascular wall changes and SMCs during vascular regeneration and in graft vessel disease. The effect of somatostatin analogues, which are potent inhibitors of GH and IGF-I production, has been investigated in short-term (octreotide and lanreotide) and long-term (octreotide only) models of uninephrectomy and diabetes both comprising early renal and glomerular growth, and subsequently an effect has been demonstrated on urinary albumin/protein excretion, a marker of kidney disease. Only octreotide inhibited the early local IGF-I accumulation and renal growth following unilateral nephrectomy in rats while lanreotide (Gronbaek et al, unpublished results) and octreotide both inhibited the renal hypertrophy after diabetes induction. Long-term octreotide studies demonstrated significant reductions in renal and glomerular growth and urinary albumin excretion in octreotide-treated control and diabetic rats, while no effect was observed in a diabetic uninephrectomized model, although using a much lower octreotide dose. Further, Igarashi et al treated uninephrectomized diabetic rats with octreotide for 3 weeks after an untreated period of 15 weeks and observed diminished kidney hypertrophy and normalization of albuminuria. It can be concluded from these studies that somatostatin analogues have pronounced effects on pathophysiological renal growth and on the development of long-term renal changes in diabetes and following uninephrectomy. As for chronic graft vessel disease and vascular growth and regeneration lanreotide has been shown to inhibit myointimal thickening following aortic or coronary balloon injury in various animal models. This effect may be partly mediated through an inhibition of vascular IGF-I production as demonstrated by Howell et al. A few studies have used a vessel allograft model and lanreotide significantly inhibited myointimal proliferation and, in addition, Hayry et al observed a decrease in IGF-I, epidermal growth factor, and platelet-derived growth factor BB following lanreotide treatment. In a rat kidney transplant model, lanreotide inhibited arterial graft myointimal thickening, however, the authors did not measure IGF-I expression. From these experiments it is hypothesized that beneficial effects of treatment with somatostatin analogues may be achieved following kidney transplantation through reducing adverse effects of GH and IGF-I on long-term changes in the transplanted kidney.