INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS IN THE HUMAN ADRENAL-GLAND

Insulin-like growth factors (IGFs) are thought to be important regulat ors of adrenocortical growth and steroidogenesis. IGFs are usually com plexed with a family of specific IGF-binding proteins (IGFBPs) in seru m. other body fluids, and in conditioned media of a variety of cell ty pes. IGFBPs may either inhibit or potentiate the effects of IGFs. In t he present study we have investigated the gene expression of the IGFBP s and IGF receptors in human fetal (HFA) and adult (HAA) adrenals. Nor thern blotting and/or reverse transcription polymerase chain reaction (RT-PCR) methods were used. IGFBP secretion into the cell culture medi um was studied in primary cell cultures by Western ligand blotting and by radioimmunoassays. IGFBP-1 mRNA expression was low in adrenals: No rthern blots were negative, bur RT-PCR revealed IGFBP-1 mRNA in HFA. I GFBP-2 mRNA was equally expressed in both HFA and HAA with no differen ces in signal intensities by Northern blotting. IGFBP-3 mRNA was detec ted in HFA but not in HAA by Northern blotting. IGFBP-4 mRNA was expre ssed equally in both HFA and HAA. IGFBP-5 and -6 mRNA expression was m ore abundant in HAA than in HFA. IGF-I and type I and type II IGF rece ptor mRNAs were equally expressed in both HFA and HAA. 12-O-tetradecan oyl phorbol-13-acetate (TPA), a protein kinase regulator, upregulated IGFBP-1 in HFA cultures as determined by RIA, but ACTH was without eff ect. IGFBP-2 was not regulated by TPA or ACTH neither at protein nor a t mRNA level. IGFBP-3 was downregulated by TPA both at protein and mRN A levels, but it was not affected by ACTH. In Western ligand blots of conditioned media from HFA cultures, we detected multiple bands. The b est visualized bind was a 47-44 kDa doublet, which most obviously repr esents IGFBP-3. Our results together with earlier findings show that a ll the components of the IGF system are expressed and produced locally in the human adrenal gland. Then are also marked differences in the e xpression pattern of IGF-II and IGFBPs between fetal and adult glands. IGFBPs mat. have important autocrine or paracrine roles in the regula tion of IGF functions in the adrenal gland.