Insulin-like Growth Factor Binding Proteins-1 and -3 and Sex Hormone-binding Globulin: Studies on Regulation of Synthesis in Vitro, and Clinical Aspects

............................................................................................................................. 7 INTRODUCTION.................................................................................................................... 8 REVIEW OF THE LITERATURE........................................................................................ 9 1. THE INSULIN-LIKE GROWTH FACTOR (IGF) SYSTEM............................................................ 9 2. IGF-I AND IGF-II................................................................................................................ 9 3. IGF RECEPTORS ................................................................................................................ 12 4. IGF BINDING PROTEINS (IGFBPS)..................................................................................... 13 5. IGFBP-1 ........................................................................................................................... 15 5.1 Gene and protein structure ......................................................................................... 15 5.2 Production sites .......................................................................................................... 16 5.3 Function...................................................................................................................... 16 5.4 Phosphorylation.......................................................................................................... 16 5.5 Regulation .................................................................................................................. 17 6. IGFBP-3 ........................................................................................................................... 19 6.1 Gene and protein structure ......................................................................................... 19 6.2 Function...................................................................................................................... 19 6.3 Regulation .................................................................................................................. 20 7. SHBG ............................................................................................................................... 21 7.1 Gene and protein structure ......................................................................................... 22 7.2 Function...................................................................................................................... 22 7.3 Production sites .......................................................................................................... 23 7.4 Regulation .................................................................................................................. 23 8. REGULATION OF IGFBP-1 AND SHBG BY INSULIN AND IGFS.......................................... 25 9. IGFBP-1 AND ESTROGENS ................................................................................................ 26 9.1 Ovarian stimulation .................................................................................................... 26 9.2. Hormone treatment.................................................................................................... 27 10. METABOLIC SYNDROME, DIABETES RISK AND MORTALITY.............................................. 27 11. IGFBP-1 AND SHBG IN METABOLIC SYNDROME AND DIABETES .................................... 29 12. THE IGF SYSTEM IN PREGNANCY .................................................................................... 30 13. THE IGF SYSTEM IN DELIVERY AND PREMATURE RUPTURE OF FETAL MEMBRANES......... 31 AIMS OF THE STUDY......................................................................................................... 33 MATERIALS AND METHODS........................................................................................... 34 1. IN VITRO STUDIES (I, II, III) ............................................................................................... 34 1.1 Cell cultures................................................................................................................ 34 1.2 Assays......................................................................................................................... 34 1.3 Statistical methods...................................................................................................... 36 2. CLINICAL STUDIES (IV, V) ................................................................................................ 37 2.1 Study Subjects ............................................................................................................ 37 2.2 Study protocols and laboratory analyses.................................................................... 38 2.3 Definitions of glucose tolerance and metabolic syndrome (IV) ................................ 39