IS THERE A LOCAL IGF-SYSTEM IN HUMAN ADRENOCORTICAL-CELLS

There is increasing evidence that in the fetal and postnatal developme nt of the adrenal gland, trophic and differentiating effects of ACTH a re locally modulated by a species-specific pattern of growth factors. As we have shown previously in human adult adrenocortical cells (HAC) in culture, IGF-I and, even more, IGF-II enhance the steroidogenesis a nd ACTH responsiveness. We now examined the secretion of IGFs and thei r binding proteins (IGFBP) in the medium of 12 serum free primary cult ures of HAC by specific RIAs and [I-125]IGF ligand blot or by immunobl ot, and their long-term regulation by ACTH. HAC secrete 0.41 and 0.91 ng IGF-I and IGF-II/5 x 10(5) cells per day, respectively, and their s ecretion is significantly stimulated 2- and 1.6-fold, respectively? by ACTH. HAC secrete at least three IGFBPs. The 43-46 kDa and the 29 kDa proteins correspond to glycosylated and fragmented forms of IGFBP-3, and the 36 kDa protein to IGFBP-2. The most abundant protein is the 24 kDa IGFBP, with identical electrophoretic mobility to IGFBP-4. IGFBP- 3, as measured by RIA, is in the range of 1 ng/day. None of the IGFBPs is significantly changed by ACTH. Thus, we have evidence for a local IGF system, and the IGF-levels are in a range compatible with a physio logical auto or paracrine action on steroidogenesis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.