Does the physiological acromegaly of pregnancy benefit the fetus?

Gynecologic and Obstetric Investigation

Volumn 66, Issue 4, 2008, Pages 217-226

  Verhaeghe, Johan ^a,b  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

Growth hormone; Insulin like growth factor; Placenta

Indexed keywords

GROWTH HORMONE; GROWTH HORMONE RELEASING FACTOR; PLACENTA LACTOGEN; PROLACTIN; SOMATOMEDIN B; SOMATOMEDIN BINDING PROTEIN 3; SOMATOMEDIN C;

BIOAVAILABILITY; BLOOD PLACENTA BARRIER; CELL INVASION; FIRST TRIMESTER PREGNANCY; GESTATIONAL ACROMEGALY; GROWTH HORMONE BLOOD LEVEL; HORMONE RELEASE; HUMAN; NONHUMAN; PHYSIOLOGICAL PROCESS; PLACENTA DEVELOPMENT; PREGNANCY; PRIORITY JOURNAL; REVIEW; SECOND TRIMESTER PREGNANCY; TROPHOBLAST; WESTERN BLOTTING;

ANIMALS; FEMALE; FETAL DEVELOPMENT; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; PLACENTA; PREGNANCY;

EID: 47549118935     PISSN: 03787346     EISSN: None     Source Type: Journal    
DOI: 10.1159/000147167     Document Type: Review

References (118)

1. Baumann G, Dávila N, Shaw MA, Ray J, Liebhaber SA, Cooke NE: Binding of human growth hormone (GH)-variant (placental GH) to GH-binding proteins in human plasma. J Clin Endocrinol Metab 1991;73:1175-1179.
2. Blackman MR, Sorkin JD, Münzer T, et al: Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 2002;288:2282-2292.
3. Jabri N, Schalch DS, Schwartz SL, et al: Adverse effects of recombinant human insulin-like growth factor I in obese insulin-resistant type II diabetic patients. Diabetes 1994;43:369-374.
4. Copeland KC, Nair KS: Recombinant human insulin-like growth factor-I increases forearm blood flow. J Clin Endocrinol Metab 1994;79:230-232.
5. Igout A, Van Beeumen J, Frankenne F, Scippo M-L, Devreese B, Hennen G: Purification and biochemical characterization of recombinant human placental growth hormone produced in Escherichia coli. Biochem J 1993;295:719-724.
6. Frankenne F, Closset J, Gomez F, Scippo ML, Smal J, Hennen G: The physiology of growth hormones (GHs) in pregnant women and partial characterization of the placental GH variant. J Clin Endocrinol Metab 1988;66:1171-1180.
7. Scippo ML, Frankenne F, Hooghe-Peeters EL, Igout A, Velkeniers B, Hennen G: Syncytiotrophoblast localization of the human growth hormone variant mRNA in the placenta. Mol Cell Endocrinol 1993;92:R7-R13.
8. Igout A, Frankenne F, L'Hermite-Balériaux M, Martin A, Hennen G: Somatogenic and lactogenic activity of the recombinant 22 kDa isoform of human placental growth hormone. Growth Regul 1995;5:60-65.
9. MacLeod JN, Worsley I, Ray J, Friesen HG, Liebhaber SA, Cooke NE: Human growth hormone-variant is a biologically active somatogen and lactogen. Endocrinology 1991;128:1298-1302.
10. Goodman HM, Tai LR, Ray J, Cooke NE, Liebhaber SA: Human growth hormone variant produces insulin-like and lipolytic responses in rat adipose tissue. Endocrinology 1991;129:1779-1783.
11. Barbour LA, Shao J, Qiao L, et al: Human placental growth hormone causes severe insulin resistance in transgenic mice. Am J Obstet Gynecol 2002;186:512-517.
12. Eriksson L, Frankenne F, Edèn S, Hennen G, von Schoultz B: Growth hormone 24-h serum profiles during pregnancy-lack of pulsatility for the secretion of the placental variant. Br J Obstet Gynaecol 1989;96:949-953.
13. Lønberg U, Damm P, Andersson A-M, et al: Increase in maternal placental growth hormone during pregnancy and disappearance during parturition in normal and growth hormone-deficient pregnancies. Am J Obstet Gynecol 2003;188:247-251.
14. Chellakooty M, Vangsgaard K, Larsen T, et al: A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth. J Clin Endocrinol Metab 2004;89:384-391.
15. Fuglsang J, Skjærbæk C, Espelund U, Frystyk J, Fisker S, Flyvbjerg A, Ovesen P: Ghrelin and its relationship to growth hormones during normal pregnancy. Clin Endocrinol (Oxf) 2005;62:554-559.
16. Massa G: Growth hormone-binding proteins during human pregnancy: maternal, fetal and neonatal data. Proc Soc Exp Biol Med 1994;206:316-319.
17. Barnard R, Chan F-Y, McIntyre HD: Growth hormone-binding protein in normal and pathologic gestation: correlations with maternal diabetes and fetal growth. J Clin Endocrinol Metab 1997;82:1879-1884.
18. Fuglsang J, Sandager P, Møller N, Fisker S, Frystyk J, Ovesen P: Peripartum maternal and foetal ghrelin, growth hormones, IGFs and insulin interrelations. Clin Endocrinol (Oxf) 2006;64:502-509.
19. Fuglsang J, Sandager P, Møller N, Fisker S, Ørskov H, Ovesen P: Kinetics and secretion of placental growth hormone around parturition. Eur J Endocrinol 2006;154:449-457.
20. de Zegher F, Vanderschueren-Lodeweyckx M, Spitz B, Faijerson Y, Blomberg F, Beckers A, Hennen G, Frankenne F: Perinatal growth hormone (GH) physiology: effect of GH-releasing factor on maternal and fetal secretion of pituitary and placental GH. J Clin Endocrinol Metab 1990;77:520-522.
21. Evain-Brion D, Alsat E, Mirlesse V, Dodeur M, Scippo ML, Hennen G, Frankenne F: Regulation of growth hormone secretion in human trophoblastic cells in culture. Horm Res 1990;33:256-259.
22. Verhaeghe J, Bougoussa M, Van Herck E, de Zegher F, Hennen G, Igout A: Placental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency. Clin Endocrinol (Oxf) 2000;53:645-647.
23. Coutant R, Boux de Casson F, Douay O, et al: Relationships between placental GH concentration and maternal smoking, newborn gender, and maternal leptin: implications for birth weight. J Clin Endocrinol Metab 2001;86:4854-4859.
24. Verhaeghe J, Pintiaux A, Van Herck E, Hennen G, Foidart J-M, Igout A: Placental GH, IGF-I, IGF-binding protein-1, and leptin during a glucose challenge test in pregnant women: relation with maternal body weight, glucose tolerance, and birth weight. J Clin Endocrinol Metab 2002;87:2875-2882.
25. Chowen JA, Evain-Brion D, Pozo J, Alsat E, Garcia-Segura LM, Argente J: Decreased expression of placental growth hormone in intrauterine growth retardation. Pediatr Res 1996;39:736-739.
26. Mirlesse V, Frankenne F, Alsat E, Poncelet M, Hennen G, Evain-Brion D: Placental growth hormone levels in normal pregnancy and in pregnancies with intrauterine growth retardation. Pediatr Res 1993;34:439-442.
27. Caufriez A, Frankenne F, Hennen G, Copinschi G: Regulation of maternal IGF-I by placental GH in normal and abnormal human pregnancies. Am J Physiol Endocrinol Metab 1993;265:E572-E577.
28. McIntyre HD, Serek R, Crane DI, et al: Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth. J Clin Endocrinol Metab 2000;85:1143-1150.
29. Chellakooty M, Skibsted L, Skouby SO, et al: Longitudinal study of serum placental GH in 455 normal pregnancies: correlation to gestational age, fetal gender, and weight. J Clin Endocrinol Metab 2002;87:2734-2739.
30. Veldhuis JD, Iranmanesh A, Ho KKY, Waters MJ, Johnson ML, Lizarralde G: Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity. J Clin Endocrinol Metab 1991;72:51-59.
31. Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebæ NE, Hilsted J: Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 1995;80:1407-1415.
32. Langendonk JG, Meinders AE, Burggraaf J, et al: Influence of obesity and body fat distribution on growth hormone kinetics in humans. Am J Physiol Endocrinol Metab 1999;277:E824-E829.
33. Verhaeghe J, van Bree R, Van Herck E: Maternal body size and birth weight: can insulin or adipokines do better? Metabolism 2006;55:339-344.
34. Gibson HM: Plasma volume and glomerular filtration rate in pregnancy and their relation to differences in fetal growth. J Obstet Gynaecol Br Commonw 1973;80:1067-1074.
35. Kaplan SA, Cohen P: The somatomedin hypothesis 2007:50 years later. J Clin Endocrinol Metab 2007;92:4529-4535.
36. Govoni KE, Wergedal JE, Florin L, Angel P, Baylink DJ, Mohan S: Conditional deletion of insulin-like growth factor-I in collagen type 1α2-expressing cells results in postnatal lethality and a dramatic reduction in bone accretion. Endocrinology 2007;148:5706-5715.
37. Fowden AL: The insulin-like growth factors and feto-placental growth. Placenta 2003;24:803-812.
38. Verhaeghe J, Van Herck E, Billen J, Moerman P, Van Assche FA, Giudice LC: Regulation of insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses. Am J Obstet Gynecol 2003;188:485-491.
39. Verhaeghe J, Loos R, Vlietinck R, Van Herck E, van Bree R, De Schutter A-M: C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in cord serum of twins: genetic versus environmental regulation. Am J Obstet Gynecol 1996;175:1180-1188.
40. Han VKM, Bassett N, Walton J, Challis JRG: The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab 1996;81:2680-2693.
41. Frystyk J, Højlund K, Rasmussen KN, Jørgensen SP, Wildner-Christensen M, Ørskov H: Development and clinical evaluation of a novel immunoassay for the binary complex of IGF-I and IGF-binding protein-1 in human serum. J Clin Endocrinol Metab 2002;87:260-266.
42. Jensen EC, Harding JE, Bauer MK, Gluckman PD: Metabolic effects of IGF-I in the growth retarded fetal sheep. J Endocrinol 1999;161:485-494.
43. Clapp JF III, Schmidt S, Paranjape A, Lopez B: Maternal insulin-like growth factor-I levels (IGF-I) reflect placental mass and neonatal fat mass. Am J Obstet Gynecol 2004;190:730-736.
44. Olausson H, Lof M, Brismar K, Lewitt M, Forsum E, Sohlstrom A: Longitudinal study of the maternal insulin-like growth factor system before, during and after pregnancy in relation to fetal and infant weight. Horm Res 2008;69:99-106.
45. Leung K-C, Johannsson G, Leong GM, Ho KKY: Estrogen regulation of growth hormone action. Endocr Rev 2004;25:693-721.
46. Wilson DM, Bennett A, Adamson GD, et al: Somatomedins in pregnancy: a cross-sectional study of insulin-like growth factors I and II and somatomedin peptide content in normal human pregnancies. J Clin Endocrinol Metab 1982;55:858-861.
47. Caufriez A, Frankenne F, Englert Y, Golstein J, Cantraine F, Hennen G, Copinschi G: Placental growth hormone as a potential regulator of maternal IGF-I during human pregnancy. Am J Physiol Endocrinol Metab 1990;258:E1014-E1019.
48. Fuglsang J, Lauszus F, Flyvbjerg A, Ovesen P: Human placental growth hormone, insulin-like growth factor-I and -II, and insulin requirements during pregnancy in type 1 diabetes. J Clin Endocrinol Metab 2003;88:4355-4361.
49. Baxter RC, Martin JL: Radioimmunoassay of growth hormone-dependent insulin-like growth factor binding protein in human plasma. J Clin Invest 1986;78:1504-1512.
50. Giudice LC, Farrell EM, Pham H, Lamson G, Rosenfeld RG: Insulin-like growth factor binding proteins in maternal serum throughout gestation and in the puerperium: effects of a pregnancy-associated serum protease activity. J Clin Endocrinol Metab 1990;71:806-816.
51. Irwin JC, Suen L-F, Cheng B-H, Martin R, Cannon P, Deal CL, Giudice LC: Human placental trophoblasts secrete a disintegrin metalloproteinase very similar to the insulin-like growth factor binding protein-3 protease in human pregnancy serum. Endocrinology 2000;141:666-674.
52. Binoux M: Tools now exist to measure circulating IGF-binding protein-3 proteolysis, to study its regulation and its effects on IGF-I bioavailability. J Clin Endocrinol Metab 2001;86:5088-5089.
53. Baxter RC: What is the significance of IGF-binding protein-3 proteolysis in the circulation? J Clin Endocrinol Metab 2001;86:5087-5088.
54. Bang P, Ahlsén M, Berg U, Carlsson-Skwirut C: Free insulin-like growth factor I: are we hunting a ghost? Horm Res 2001;55(suppl 2):84-93.
55. Hasegawa T, Hasegawa Y, Takada M, Tsuchiya Y: The free form of insulin-like growth factor I increases in circulation during normal human pregnancy. J Clin Endocrinol Metab 1995;80:3284-3286.
56. Davenport ML, Clemmons DR, Miles MV, Camacho-Hubner C, D'Ercole AJ, Underwood LE: Regulation of serum insulin-like growth factor-I (IGF-I) and IGF binding proteins during rat pregnancy. Endocrinology 1990;127:1278-1286.
57. Koistinen R, Angervo M, Leinonen P, Hakala T, Seppälä M: Phosphorylation of insulin-like growth factor-binding protein-1 increases in human amniotic fluid and decidua from early to late pregnancy. Clin Chim Acta 1993;215:189-199.
58. Westwood M, Gibson JM, Davies AJ, Young RJ, White A: The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy. J Clin Endocrinol Metab 1994;79:1735-1741.
59. Martina NA, Kim E, Chitkara U, Wathen NC, Chard T, Giudice LC: Gestational age-dependent expression of insulin-like growth factor binding protein-1 (IGFBP-1) phosphoisoforms in human extraembryonic cavities, maternal serum, and decidua suggests decidua as the primary source of IGFBP-1 in these fluids during early pregnancy. J Clin Endocrinol Metab 1997;82:1894-1898.
60. Crossey PA, Pillai CC, Miell JP: Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice. J Clin Invest 2002;110:411-418.
61. Rutanen E-M, Bohn H, Seppälä M: Radioimmunoassay of placental protein 12: levels in amniotic fluid, cord blood, and serum of healthy adults, pregnant women, and patients with trophoblastic disease. Am J Obstet Gynecol 1982;144:460-463.
62. Wang HS, Perry LA, Kanisius J, Iles RK, Holly JMP, Chard T: Purification and assay of insulin-like growth factor-binding protein-1: measurement of circulating levels throughout pregnancy. J Endocrinol 1991;128:161-168.
63. Bhatia S, Faessen GH, Carland G, et al: A longitudinal analysis of maternal serum insulin-like growth factor I (IGF-I) and total and nonphosphorylated IGF-binding protein-1 in human pregnancies complicated by intrauterine growth restriction. J Clin Endocrinol Metab 2002;87:1864-1870.
64. Wathen NC, Egembah S, Campbell DJ, Farkas A, Chard T: Levels of insulin-like growth factor-binding protein-1 increase rapidly in amniotic fluid from 11 to 16 weeks of pregnancy. J Endocrinol 1993;137:R1-R4.
65. Verhaeghe J, Coopmans W, Van Herck E, Van Schoubroeck D, Deprest JA, Witters I: IGF-I, IGF-II, IGF binding protein 1, and C-peptide in second trimester amniotic fluid are dependent on gestational age but do not predict weight at birth. Pediatr Res 1999;46:101-108.
66. Lockwood CJ, Wein R, Chien D, Ghidini A, Alvarez M, Berkowitz RL: Fetal membrane rupture is associated with the presence of insulin-like growth factor-binding protein-1 in vaginal secretions. Am J Obstet Gynecol 1994;171:146-150.
67. Rutanen E-M, Kärkkäinen TH, Lehtovirta J, Uotila JT, Hinkula MK, Hartikainen A-L: Evaluation of a rapid strip test for insulin-like growth factor binding protein-1 in the diagnosis of ruptured fetal membranes. Clin Chim Acta 1996;253:91-101.
68. 12): factors affecting levels in late pregnancy. Placenta 1984;5:243-248.
69. Gibson JM, Westwood M, Lauszus FF, Klebe JG, Flyvbjerg A, White A: Phosphorylated insulin-like growth factor-binding protein 1 is increased in pregnant diabetic subjects. Diabetes 1999;48:321-326.
70. Baldwin S, Chung T, Rogers M, Chard T, Wang HS: Insulin-like growth factor-binding protein-1, glucose tolerance and fetal growth in human pregnancy. J Endocrinol 1993;136:319-325.
71. Wheeler T, Chard T, Anthony F, Osmond C: Relationships between the uterine environment and maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 in early pregnancy. Hum Reprod 1995;10:2700-2704.
72. Hills FA, English J, Chard T: Circulating levels of IGF-I and IGF-binding protein-1 throughout pregnancy: relation to birth-weight and maternal weight. J Endocrinol 1996;148:303-309.
73. Rasmussen MH, Juul A, Hilsted J: Effect of weight loss on free insulin-like growth factor-I in obese women with hyposomatotropism. Obesity 2007;15:879-886.
74. de Groot CJM, O'Brien TJ, Taylor RN: Biochemical evidence of impaired trophoblastic invasion of decidual stroma in women destined to have preeclampsia. Am J Obstet Gynecol 1996;175:24-29.
75. Hietala R, Pohja-Nylander P, Rutanen E-M, Laatikainen T: Serum insulin-like growth factor binding protein-1 at 16 weeks and subsequent preeclampsia. Obstet Gynecol 2000;95:185-189.
76. Anim-Nyame N, Hills FA, Sooranna SR, Steer PJ, Johnson MR: A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia. Hum Reprod 2000;15:2215-2219.
77. Grobman WA, Kazer RR: Serum insulin, insulin-like growth factor-I, and insulin-like growth factor binding protein-1 in women who develop preeclampsia. Obstet Gynecol 2001;97:521-526.
78. Ning Y, Williams MA, Vadachkoria S, Muy-Rivera M, Frederick IO, Luthy DA: Maternal plasma concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein-1 in early pregnancy and subsequent risk of preeclampsia. Clin Biochem 2004;37:968-973.
79. Vatten LJ, Nilsen TIL, Juul A, Jeansson S, Jenum PA, Eskild A: Changes in circulating level of IGF-I and IGF-binding protein-1 from the first to the second trimester as predictors of preeclampsia. Eur J Endocrinol 2008;158:101-105.
80. Iino K, Sjöberg J, Seppälä M: Elevated circulating levels of a decidual protein, placental protein 12, in preeclampsia. Obstet Gynecol 1986;68:58-60.
81. Howell RJS, Economides D, Teisner B, Farkas AG, Chard T: Placental proteins 12 and 14 in pre-eclampsia. Acta Obstet Gynecol Scand 1989;68:237-240.
82. Wang H-S, Lee J-D, Cheng B-J, Soong Y-K: Insulin-like growth factor-binding protein 1 and insulin-like growth factor-binding protein 3 in pre-eclampsia. Br J Obstet Gynaecol 1996;103:654-659.
83. Giudice LC, Martina NA, Crystal RA, Tazuke S, Druzin M: Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia. Am J Obstet Gynecol 1997;176:751-758.
84. Stone S, Langford K, Seed PT, Khamashta MA, Hunt BJ, Poston L: Longitudinal analysis of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in antiphospholipid syndrome and in healthy pregnancy. Am J Obstet Gynecol 2003;189:274-279.
85. Cozzi R, Attanasio R, Barausse M: Pregnancy in acromegaly: a one-center experience. Eur J Endocrinol 2006;155:279-284.
86. Obuobie K, Mullik V, Jones C, et al: McCune-Albright syndrome: growth hormone dynamics in pregnancy. J Clin Endocrinol Metab 2001;86:2456-2458.
87. Clemmons DR, Underwood LE, Ridgway EC, Kliman B, Kjellberg RN, Van Wyk JJ: Estradiol treatment of acromegaly: reduction of immunoreactive somatomedin-C and improvement in metabolic status. Am J Med 1980;69:571-575.
88. Gualillo O, Caminos JE, Blanco M, et al: Ghrelin, a novel placental-derived hormone. Endocrinology 2001;142:788-794.
89. Larsen T, Main K, Andersson AM, Juul A, Greisen G, Skakkebæk NE: Growth hormone, insulin-like growth factor I and its binding proteins 1 and 3 in last trimester intrauterine growth retardation with increased pulsatility index in the umbilical artery. Clin Endocrinol (Oxf) 1996;45:315-319.
90. Holmes RP, Holly JMP, Soothill PW: A prospective study of maternal serum insulin-like growth factor-I in pregnancies with appropriately grown or growth restricted fetuses. Br J Obstet Gynaecol 1998;105:1273-1278.
91. Papadopoulou E, Sifakis S, Giahnakis E, Fragouli Y, Karkavitsas N, Koumantis E, Kalmanti M: Increased human placental growth hormone at midtrimester pregnancies may be an index of intrauterine growth retardation related to preeclampsia. Growth Horm IGF Res 2006;16:290-296.
92. Fowler D, Albaiges G, Lees C, Jones J, Nicolaides K, Miell J: The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by Doppler ultrasound. Hum Reprod 1999;14:2881-2885.
93. Hakala-Ala-Pietilä TH, Koistinen RA, Salonen RK, Seppälä MT: Elevated second-trimester amniotic fluid concentration of insulin-like growth factor binding protein-1 in fetal growth retardation. Am J Obstet Gynecol 1993;169:35-39.
94. Chevallier B, Lagarde A, Degrelle H, Belaisch-Allart J, Giraudet P, Gallet J-P : Insulin-like growth factor binding protein 1 level in amniotic fluid: correlation with birth weight. Biol Neonate 1998;73:404-406.
95. Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE: Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care 2007;30(suppl 2):S112-S119.
96. Freinkel N: Of pregnancy and progeny. Diabetes 1980;29:1023-1035.
97. Hansen I, Tsalikian E, Beaufrere B, Gerich J, Haymond M, Rizza R: Insulin resistance in acromegaly: defects in both hepatic and extrahepatic insulin action. Am J Physiol Endocrinol Metab 1986;250:E269-E273.
98. Rizza RA, Mandarino LJ, Gerich JE: Effects of growth hormone on insulin action in man: mechanisms of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilization. Diabetes 1982;31:663-669.
99. Nørrelund H, Djurhuus C, Jørgensen JOL, et al: Effects of GH on urea, glucose and lipid metabolism, and insulin sensitivity during fasting in GH-deficient patients. Am J Physiol Endocrinol Metab 2003;285:E737-E743.
100. Barbour LA, Shao J, Qiao L, Leitner W, Anderson M, Friedman JE, Draznin B: Human placental growth hormone increases expression of the P85 regulatory unit of phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal muscle. Endocrinology 2004;145:1144-1150.
101. McIntyre HD, Russell A, Serek R, Veveris-Lowe T, Cotterill A, Cowley D, Barnard R: Placental growth hormone is not suppressed by oral glucose loading in normal human pregnancy. Horm Metab Res 2002;34:250-253.
102. Patel N, Alsat E, Igout A, Baron F, Hennen G, Porquet D, Evain-Brion D: Glucose inhibits human placental GH secretion, in vitro. J Clin Endocrinol Metab 1995;80:1743-1746.
103. Sferuzzi-Perri AN, Owens JA, Pringle KG, Robinson JS, Roberts CT: Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth. Endocrinology 2006;147:3344-3355.
104. Sferuzzi-Perri AN, Owens JA, Standen P, Taylor RL, Heinemann GK, Robinson JS, Roberts CT: Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. Am J Physiol Endocrinol Metab 2007;292:E668-E676.
105. Frankenne F, Alsat E, Scippo M-L, Igout A, Hennen G, Evain-Brion D: Evidence for the expression of growth hormone receptors in human placenta. Biochem Biophys Res Comm 1992;182:481-486.
106. Urbanek M, Russell JE, Cooke NE, Liebhaber SA: Functional characteristics of the alternatively spliced, placental growth hormone receptor. J Biol Chem 1993;268:19025-19032.
107. Lacroix M-C, Guibourdenche J, Fournier T, et al: Stimulation of human trophoblast invasion by placental growth hormone. Endocrinology 2005;146:2434-2444.
108. Lacey H, Haigh T, Westwood M, Aplin JD: Mesenchymally-derived insulin-like growth factor I provides a paracrine stimulus for trophoblast migration. BMC Dev Biol 2002;2:5.
109. Hamilton GS, Lysiak JJ, Han VKM, Lala PK: Autocrine-paracrine regulation of human trophoblast invasiveness by insulin-like growth factor (IGF)-II and IGF-binding protein (IGFBP)-1. Exp Cell Res 1998;244:147-156.
110. Gibson JM, Aplin JD, White A, Westwood M: Regulation of IGF biovailability in pregnancy. Mol Hum Reprod 2001;7:79-87.
111. Constância M, Hemberger M, Hughes J, et al: Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature (Lond) 2002;417:945-948.
112. Sibley CP, Coan PM, Ferguson-Smith AC, et al: Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta. PNAS 2004;101:8204-8208.
113. Roberts CT, Kind KL, Earl RA, et al: Circulating insulin-like growth factor (IGF)-I and IGF binding proteins-1 and -3 and placental development in the guinea-pig. Placenta 2002;23:763-770.
114. Sferuzzi-Perri AN, Owens JA, Standen P, Taylor RL, Robinson JS, Roberts CT: Early pregnancy maternal endocrine insulin-like growth factor I programs the placenta for increased functional capacity throughout gestation. Endocrinology 2007;148:4362-4370.
115. Bauer MK, Harding JE, Bassett NS, et al: Fetal growth and placental function. Mol Cell Endocrinol 1998;140:115-120.
116. Karl PI: Insulin-like growth factor-1 stimulates amino acid uptake by the cultured human placental trophoblast. J Cell Physiol 1995;165:83-88.
117. Yu J, Iwashita M, Kudo Y, Takeda Y: Phosphorylated insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) inhibits while non-phosphorylated IGFBP-1 stimulates IGF-I-induced amino acid uptake by cultured trophoblast cells. Growth Horm IGF Res 1998;8:65-70.
118. Matthews JC, Beveridge MJ, Dialynas E, Bartke A, Kilberg MS, Novak DA: Placental anionic and cationic amino acid transporter expression in growth hormone overexpressing and null IGF-II or null IGF-I receptor mice. Placenta 1999;20:639-650.