Horm Metab Res 2008; 40(3): 189-193
DOI: 10.1055/s-2007-1004575
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Effects of Glucose, Glycerol, 3-Hydroxybutyrate, Insulin, and Leptin on Placental Growth Hormone Secretion in Placental Explants

J. Fuglsang 1 , N. Møller 2 , T. Ledet 3 , P. Ovesen 4
  • 1Gynaecological/Obstetrical Research Laboratory Y, Gynaecological/Obstetrical Department Y, Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark
  • 2Institute of Clinical Medicine, Medical Research Laboratories, Aarhus University Hospital, Aarhus Sygehus, Nørrebrogade, Aarhus C, Denmark
  • 3Research Laboratories for Biochemical Pathology, Aarhus University Hospital, Aarhus Sygehus, Nørrebrogade, Aarhus C, Denmark
  • 4Gynaecological/Obstetrical Department Y, Aarhus University Hospital, Skejby Sygehus, Aarhus N, Denmark
Further Information

Publication History

received 10.04.2007

accepted 19.07.2007

Publication Date:
04 February 2008 (online)

Abstract

Placental growth hormone (PGH) is secreted from the syncytiotrophoblast in increasing amounts during pregnancy. The physiology and regulation of PGH is not well known; however, low glucose levels appear to stimulate PGH liberation in vitro and in vivo. PGH appears to have lipolytic effects, and inverse correlations between maternal body mass index and serum PGH levels have been reported. Therefore, substances related to maternal adipose tissue metabolism could influence PGH secretion. The effect of insulin, glycerol, 3-hydroxybutyrate (3-OHB), and leptin on PGH and human placental lactogen (hPL) secretion from cultured placental explants was studied. In glucose-free media, PGH content increased upto 237.5±28.4% of control media (p<0.001, ANOVA). Insulin levels were without effect on PGH secretion, as were 3-OHB, leptin, and glycerol at 0.02 mmol/l. Glycerol at 0.2 mmol/l increased PGH in all of the placental explants studied (n=8; mean increase 27.3±7.1%), and this difference was significantly different from the control explants (p=0.004). The liberation of hPL to culture media was different from PGH and was influenced by glucose and insulin. In conclusion, the absence of glucose profoundly increased PGH secretion in cultured placental explants. Addition of glycerol in physiologically relatively high concentrations showed a less pronounced stimulatory effect.

References

  • 1 MacIntyre HD, Serek R, Crane DI, Veveris-Lowe T, Parry A, Johnson S, Leung KC, Ho KK, Bougoussa M, Hennen G, Igout A, Chan FY, Cowley D, Cotterill A, Barnard R. 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
  • 2 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
  • 3 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
  • 4 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. 1993;  265 E572-E577
  • 5 Chellakooty M, Vangsgaard K, Larsen T, Scheike T, Falck-Larsen J, Legarth J, Andersson AM, Main KM, Skakkebaek NE, Juul A. 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
  • 6 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
  • 7 Bjorklund AO, Adamson UK, Carlstrom KA, Hennen G, Igout A, Lins PE, Westgren LM. Placental hormones during induced hypoglycaemia in pregnant women with insulin-dependent diabetes mellitus: evidence of an active role for placenta in hormonal counter-regulation.  Br J Obstet Gynaecol. 1998;  105 649-655
  • 8 Zegher F de, 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;  71 520-522
  • 9 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
  • 10 Beckers A, Stevenaert A, Foidart JM, Hennen G, Frankenne F. Placental and pituitary growth hormone secretion during pregnancy in acromegalic women.  J Clin Endocrinol Metab. 1990;  71 725-731
  • 11 Fuglsang J, Skjaerbaek 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
  • 12 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
  • 13 Quabbe HJ, Trompke M, Luyckx AS. Influence of ketone body infusion on plasma growth hormone and glucagon in man.  J Clin Endocrinol Metab. 1983;  57 613-618
  • 14 Moller N, Jorgensen JO, Moller J, Bak JF, Porksen N, Alberti KG, Schmitz O. Substrate metabolism during modest hyperinsulinemia in response to isolated hyperketonemia in insulin-dependent diabetic subjects.  Metabolism. 1990;  39 1309-1313
  • 15 Fuglsang J, Sandager P, Moller 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
  • 16 Jara CS, Salud AT, Bryant-Greenwood GD, Pirens G, Hennen G, Frankenne F. Immunocytochemical localization of the human growth hormone variant in the human placenta.  J Clin Endocrinol Metab. 1989;  69 1069-1072
  • 17 Santolaya-Forgas J, Mehta SH, Castracane VD. A study to determine if acute maternal and fetal hyperglycemia/insulinemia induces leptin production during pregnancy.  Horm Metab Res. 2006;  38 598-602
  • 18 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
  • 19 MacIntyre 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
  • 20 Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin.  Clin Chem. 2004;  50 1511-1525
  • 21 Linnemann K, Malek A, Sager R, Blum WF, Schneider H, Fusch C. Leptin production and release in the dually in vitro perfused human placenta.  J Clin Endocrinol Metab. 2000;  85 4298-4301
  • 22 Schulz S, Hackel C, Weise W. Hormonal regulation of neonatal weight: placental leptin and leptin receptors.  BJOG. 2000;  107 1486-1491
  • 23 Manderson JG, Patterson CC, Hadden DR, Traub AI, Leslie H, MacCance DR. Leptin concentrations in maternal serum and cord blood in diabetic and nondiabetic pregnancy.  Am J Obstet Gynecol. 2003;  188 1326-1332
  • 24 Verhaeghe J, Pintiaux A, Herck E, Hennen G, Foidart JM, Igout A. Placental GH, IGF-I, IGF-binding protein 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 Coutant R, Boux de Casson F, Douay O, Mathieu E, Rouleau S, Beringue F, Gillard P, Limal JM, Descamps P. Relationships between placental GH concentration and maternal smoking, newborn gender and maternal leptin: Possible implications for birth weight.  J Clin Endocrinol Metab. 2001;  86 4854-4859
  • 26 Nickel BE, Kardami E, Cattini PA. Differential expression of human placental growth-hormone variant and chorionic somatomammotropin in culture.  Biochem J. 1990;  267 653-658
  • 27 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. 1990;  258 E1014-E1019
  • 28 Barnea ER, Perlman R, Bick T, Hochberg Z. Effects of human growth hormone upon term placental hormone secretion in vitro.  Gynecol Obstet Invest. 1989;  27 133-136
  • 29 Belleville F, Lasbennes A, Nabet P, Paysant P. HCS-HCG regulation in cultured placenta.  Acta Endocrinol (Copenh). 1978;  88 169-181
  • 30 Zeitler P, Markoff E, Handwerger S. Characterization of the synthesis and release of human placental lactogen and human chorionic gonadotropin by an enriched population of dispersed placental cells.  J Clin Endocrinol Metab. 1983;  57 812-818
  • 31 Bhaumick B, Dawson EP, Bala RM. The effects of insulin-like growth factor-I and insulin on placental lactogen production by human term placental explants.  Biochem Biophys Res Commun. 1987;  144 674-682
  • 32 Hochberg Z, Perlman R, Brandes JM, Benderli A. Insulin regulates placental lactogen and estradiol secretion by cultured human term trophoblast.  J Clin Endocrinol Metab. 1983;  57 1311-1313
  • 33 Handwerger S, Freemark M. The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development.  J Pediatr Endocrinol Metab. 2000;  13 343-356

Correspondence

J. FuglsangMD, PhD 

Gynaecological/Obstetrical Research Laboratory Y

Gynaecological/Obstetrical Department Y

Aarhus University Hospital

Skejby Sygehus

8200 Aarhus N

Denmark

Phone: +45/8949/63 98

Fax: +45/8949/63 73

Email: Fuglsang@ki.au.dk

    >