Effect of progesterone on insulin-like growth factors(IGFs) and IGF-binding proteins(IGFBPs) in female rat

암컷 랫트에서 Progesterone투여가 Insulin-like Growth Factors(IGFs) 및 IGF-binding proteins(IGFBPs)에 미치는 효과

  • Jin, Song-Jun (Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Park, Soo-Hyun (Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University) ;
  • Kang, Chang-Won (Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
  • 김송군 (전북대학교 수의과대학, 생체안전성연구소) ;
  • 박수현 (전북대학교 수의과대학, 생체안전성연구소) ;
  • 강창원 (전북대학교 수의과대학, 생체안전성연구소)
  • Accepted : 2002.11.28
  • Published : 2002.12.30


The sex steroid hormone progesterone is essential for normal development and maturation of the endometrium in preparation for the embryo implantation and the maintenance of pregnancy. Insulin-like growth factor (IGF) system that is composed of IGF-I, IGF-II, IGF binding proteins (IGFBPs) is also involved in the maintenance of pregnancy. In addition, liver, kidney, and uterus is a target tissue for IGF system. However, the effect of exogenous progesterone on IGF system was not elucidated in female rats. Therefore, we investigated the effect of progesterone on insulin-like growth factors (IGFs) and IGF-binding proteins in serum, liver, kidney, and uterus in female ovariectomized rats. IGFs concentration was measured by radioimmuoassay (RIA) and IGFBPs levels by western ligand blotting(WLB). IGF-I concentration was increased in serum, liver, and uterus, but not in kidney of progesterone-treated ovariectomized rats, compared to control (P<0.05). IGF-II concentration was decreased in liver, but not in serum, kidney, and uterus of progesterone-treated rats, compared to control (P<0.05). IGFBP-3 was increased in serum, but not in liver of progesterone-treated rats, compared to control. IGFBP-2 was decreased in kidney, but not in others tissues of progesterone-treated rats, compared to control. These results suggest that progesterone may exert diverse physiological functions via the tissue-specific regulation of IGFs/IGFBPs system in female rats.



  1. Wynn RM. The human endometrium. Cyclic and gestational changes. In Biology of the Uterus, pp. 289-331, 1989
  2. Sauer MV. Use of progesterone in assisted reproduction. J Reprod Med. 44:197-202, 1999
  3. MacLaughlin DT, Sylvan PE, Richardson GS. The search for progesterone-dependent proteins secreted by human endometrium. Adv Exp Med Biol, 138:113-131, 1981
  4. Giordano G, Barreca A, Minuto F. Growth factors in the ovary. J Endocr Invest, 15:689-707, 1992
  5. Giudice LC, Saleh W. Growth factors in reproduction. Trends Endocrinol Metab, 6:60-69, 1995
  6. Baxter RC, Martin JL, Beniac VA. High molecular weight insulin-like growth factor (IGF) binding protein from bone cellconditioned medium: a prtential local regulator of IGF action. Proc Natl Acad Sci, 86:8338-8342, 1989
  7. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev, 16:3-34, 1995
  8. Hirschberg R. Insulin-like growth factor I in the kidney. Miner Electrolyte Metab, 22:128-132, 1995
  9. Barengolts EI, Kouznetsova T, Segalene A, et al. Effects of progesterone on serum levels of IGF-I and on femur IGF-I mRNA in ovariectomized rats. Blackwell Science Inc, 11:1406-1412, 1996
  10. Rutanen EM. Insulin-like growth factors in endometrial function. Gynecol Endocrinol. 12(6):399-406, 1998
  11. Adesanya OO, Zhou J, Bondy CA. Sex steroid regulation of insulin-like growth factor system gene expression and proliferation in primate myometrium. J Clin Endocrinol Metab. 81:1967-1974, 1996
  12. Reed MJ, Christodoulides A, Koistinen R, et al. The effect of endocrine therapy with medroxyprogesterone acetate, 4-hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer. Int J Cancer, 52(2):208-212, 1992
  13. Kapur S, Tamada H, Dey SK, et al. Expression of insulin-like growth factor-I(IGF-I) and its receptor in the peri-implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone. Biol Reprod, 46:208-219, 1992
  14. Cardona-Gomez GP, Chowen JA, Garcia-Segura LM. Estradiol and progesterone regulate the expression of insulin-like growth factor-I receptor and insulin-like growth factor binding protein-2 in the hypothalamus of adult female rats. J Neurobiol. 43:269-281, 2000
  15. Ohleth KM, Bagnell CA. Relaxin-induced deoxyribonucleic acid synthesis in porcine granulosa cells is mediated by insulin-like growth factor-I. Biol Reprod, 53:1286-1292, 1995
  16. Lee CY, Henricks DM. Comparisions of various acidic treatments of bovine serum on insulin-like growth factor-I hnmunoreactive and binding activity. J Endocrinol, 127:139-148, 1990
  17. Hossenlopp P, Seurin D, Segovia-Quinson B, et al. Analysis of serum insulin-like growth factor binding proteins using western blotting: use of the method for titration of the binding proteins and competitive binding studies. Anal Biochem, 154:138-143, 1986
  18. Rosen CJ, Pollak M. Circulating IGF-I: New Perspectives for a New Century. Trends Endocrinol Metab. 10:136-41, 1999
  19. Lee CY. The insulin-like growth factor system at the interface of growth, metabolism and nutrition. J. Anim. Sci. & Technol, (Kor.) 42:795-816, 2000
  20. Collet-Solberg PF, Cohen P. The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF actions. In: Vassallo J, editor. Endocrinology and Metabolism Clinics of North America. Growth and Growth Disorders, Philadelphia: W. B. Saunder Company, pp 591-614, 1996
  21. Giudice LC, Irwin JC, Dsupin BA, et al. Insulin-like growth factor(IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. Hum Reprod, 8:1796-1806, 1993
  22. Gao JG, Zhu HH, Fan J, et al. Progestin and antiprogestin differentially regulate the expression of insulin-like growth factors(IGF-I and IGF-II) messenger ribonucleic acid in human endometrial stromal cells. Biol Repord, 53:355-360, 1995
  23. Brown AL, Fraham DG, Nissley SP, et al. Developmental regulation of insulin-like growth factor II mRNA indefferent rat tissues. J Biol Chem, 261:13144-13150, 1986
  24. Lee CY, Chung CS, Simmen FA. Ontogeny of the porcine insulin-like growth factor system. Mol Cell Endocrinol, 93:71-80, 1993
  25. Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide messenger ribonucleic acid and gene structure serum, and tissue concentrations. Endocr Rev, 10:68-91, 1989
  26. Lee CY, Bazer FW, Etherton TD, et al. Ontogeny of insulin-like growth factors (IGF-I and IGF-II) and IGF-binding proteins in porcine serum during fetal and postnatal development. Endocrinology, 128:2336-2344, 1991
  27. Reinhardt RR, Bondy CA. Insulin-like growth factors cross the blood-brain barrier. Endocrinology, 135:1753-1761, 1994
  28. Carro E, Nunez A, Busiguina S, et al. Circulating insulin-like growth factor mediates effects of exercise on the brain. J Neurosci, 20:2926-2933, 2000
  29. Becker K, Stegenga S, Conway, S. Role of insulin-like growth factor I in regulating growth hormone release and feedback in the male rat. Neuro endocrinology 61:573-583, 1995
  30. Martinoli MG, Pelletier G. Dihydrotestosterone (DHT) regulation of insulin-like growth factor II mRNA in neonatal rats. Peptides. 12:1267-1271, 1991
  31. Kitraki E, Philippidis H, Stylianopoulou F. Hormonal control of insulin-like growth factor-II gene expression in the rat liver. J Mol Endocrinol. 9:131-6, 1992
  32. Oluyemisi O, Adesanya JZ, Carolyn AB. Sex steroid regulation of insulin-like growth factor system gene expression and proliferation in primate myometrium. J Clin Endocrinol Metab, 81;1967-1974, 1996
  33. Leung KC, Ho KK. Measurement of growth hormone, insulin-like growth factor I and their binding proteins: the clinical aspects. Clin Chim Acta. 313:119-23, 2001
  34. Albiston AL, Herington AC. Tissue distribution and regulation of insulin-like growth factor(IGF)-binding protein-3 messenger nibonucleic acid(mRNA) in the rat: comparison with IGF-I mRNA expression. Endocrinology, 130:497-502, 1992
  35. Arany E, Zabel P, Hill DJ. Rapid clearance of human insulin-like growth factor binding protein-3 from the rat circulation and cellular localization in liver, kidney and stomach. Growth Regul. 6:32-41, 1996
  36. Lemmey AB, Glassford J, Flick-Smith HC, et al. Differential regulation of tissue insulin-like growth factor-binding protein (IGFBP)-3, IGF-I and IGF type 1 receptor mRNA levels, and serum IGF-I and IGFBP concentrations by growth hormone and IGF-I. J Endocrinol. 154:319-328, 1997
  37. Landau D, Chin E, Bondy C, et al. Expression of insulin-like growth factor binding proteins in the rat kidney: effects of long-term diabetes. Endocrinology. 136(5):1835-1842, 1995
  38. McLellan KC, Hooper SB, Bocking AD, et al. Prolonged hypoxia induced by the reduction of maternal uterine blood flow alters insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-2 gene expression in the ovine fetus. Endocrinology. 131:1619-1628, 1992
  39. Fervenza FC, Tsao T, Hoffman AR, et al. Regional changes in the intrarenal insulin-like growth factor-I axis in diabetes. Kidney Int. 51(3):811-818, 1997
  40. Giudice LD, Milkowski DA, Lamson G, et al. Insulin like growth factor binding proteins in human endometrium: steroid-dependent messenger ribonucleic acid expression and protein synthesis. J Clin Endocrinol Metab, 72(4):779-787, 1991
  41. Giudice LC, Irwin JC, Dsupin BA, et al. Insulin-like growth factors(IGFs), IGF binding proteins(IGFBPs) and IGFBP protease in human uterine endometrium: their potential relevance to endometrial cyclic function and maternal-embryonic interactions. In Baxter RC, Gluckman PD, Rosenfeld RG eds. The insulin-like growth factors and their regulatory proteins. Amsterdam: Elsevier Science, 351-361, 1994
  42. Cann CH, Fairclough RJ, Browne CA. et al. Uterine luminal content of insulin-like growth factor (IGF)-I and endometrial expression of mRNA encoding IGF-binding proteins 1 and 2 during the oestrous cycle and early pregnancy in the ewe. Reprod Fertil Dev. 10:155-163, 1998