IGF-I stimulation of luteinizing hormone secretion, IGF-binding proteins (IGFBPs) and expression of mRNAs for IGFs, IGF receptors and IGFBPs in the ovine pituitary gland

Circulating concentrations of insulin-like growth factor-I (IGF-I) are redu ced in juvenile sheep during nutritional growth restriction and the associa ted delay in puberty. Since exogenous IGF-I has been shown to stimulate lut einizing hormone (LH) secretion, it is postulated that endogenous IGF-I may act as a stimulatory metabolic signal to the pubertal ovine hypothalamo-pi tuitary axis, yet its site of action is unknown. Using coronal hypothalamic and pituitary sections from pubertal ewe lambs, in vitro autoradiography w as used to localise I-125-labelled IGF-I binding, and gene expression for c omponents of the IGF system was localised by in situ hybridisation using ol igonucleotide probes. High concentrations of I-125-IGF-I binding were seen in the pars tuberalis (PT) and pars distalis (PD) of the pituitary, and rel atively little in the hypothalamus; binding in the PT but not the PD was di splaced by excess unlabelled IGF-I. Large amounts of mRNA were detected For the type-1 receptor (IGF-1R) and for IGF-binding protein (IGFBP)-5, locali sed to the PT and PD, and less intense specific hybridisation signals were obtained with mRNAs for IGF-II, type-2 receptor (IGF-2R) and IGFBP-3. There was some evidence for specific hybridisation to IGFBP-4 mRNA in the PT. IG F-I, IGFBP-1 and IGFBP-2 mRNAs were not detected in PT and PD. None of the genes were expressed in hypothalamic tissue. Western-ligand binding on PD e xtracts from male castrates revealed by their molecular weights the likely presence of IGFBPs-2, -3, and -5. Finally, cultured PD cells from abattoir- killed sheep were challenged with IGF-I (0.1, 1, 10 or 30 nM) or luteinizin g hormone-releasing hormone (LHRH, 10 nM) alone, or both together. Basal LH output was stimulated by 10 nM IGF-I (120 +/- 11.2%, P>0.05), 30 nM IGF-I (148 +/- 12.8%, P<0.01), and LHRH alone (200 +/- 16.1%, P<0.001); there was no additive or subtractive effect of LHRH and IGF-I given together. Thus, an intrapituitary ICF system exists in sheep and the present results are co nsistent with an endocrine role for IGF-I in nutritional modulation of LH s ecretion at the level of the pituitary gland.