EXPRESSION AND REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) ANDIGF-BINDING PROTEIN MESSENGER-RIBONUCLEIC-ACID LEVELS IN TISSUES OF HYPOPHYSECTOMIZED RATS INFUSED WITH IGF-I AND GROWTH-HORMONE

The expression and regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 (IGFBP-2), -3, -4, and -5 messages were stud ied in liver, kidney, spleen, thymus, heart, brain, skeletal muscle, t estes, and epididymal (white) adipose tissue (WAT) from hypophysectomi zed rats infused with saline, recombinant human (rh) IGF-I, or rhGH an d compared with tissue messenger RNA (mRNA) levels in age-matched norm al rats. The IGF-I message was present in all of these tissues. It was most abundant in liver and WAT, but was barely detectable in kidney, brain, and thymus. GH dependence was most pronounced in liver, skeleta l muscle, and WAT and less so in heart, testes, kidney, spleen, and th ymus. The IGF-I message in brain was not influenced by hypophysectomy. IGF-I infusion induced a small increase in its own mRNA in skeletal m uscle and WAT, whereas it decreased its own message in liver. IGFBPs w ere expressed in a tissue-specific manner; IGFBP-2 mRNA was most abund ant in testes and hypophysectomized liver, IGFBP-3 mRNA was most abund ant in spleen, kidney, WAT, and liver, IGFBP-4 mRNA was most abundant in liver, and IGFBP-5 mRNA was most abundant in kidney, WAT, and skele tal muscle. After hypophysectomy, significant decreases in IGFBP expre ssion were observed in liver (except IGFBP-2), skeletal muscle, brain, WAT (except IGFBP-4), and testes (except IGFBP-2), in contrast to hea rt, kidney, spleen, and thymus. GH infusion did not affect IGFBP-2 mRN A levels in liver (in contrast to IGF-I infusion) or brain. Like GH, I GF-I normalized IGFBP-3 mRNA levels in liver, but, in contrast to GH, had no effect on IGFBP-5 mRNA in WAT. It was considerably less effecti ve than GH in raising IGFBP-5 mRNA levels in skeletal muscle. Thus, GH infusion can exert different effects on IGF-I and IGFBP expression th an infused rhIGF-I. Differences may be due to direct actions of GH at the tissue level, including auto/paracrine effects of locally produced IGF-I.