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Ontogeny and nutritional manipulation of the hepatic prolactin–growth hormone–insulin-like growth factor axis in the ovine fetus and in neonate and juvenile sheep

Published online by Cambridge University Press:  07 March 2007

Melanie A. Hyatt ,
David A. Walker ,
Terence Stephenson  and
Michael E. Symonds
Melanie A. Hyatt
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH, UK Children's Brain Tumour Research Centre, University Hospital, Nottingham NG7 2UH, UK
David A. Walker
Affiliation:
Children's Brain Tumour Research Centre, University Hospital, Nottingham NG7 2UH, UK
Terence Stephenson
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH, UK
Michael E. Symonds
Affiliation:
Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH, UK
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Abstract

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The somatotrophic axis is the main endocrine system regulating postnatal growth; however, prenatal growth is independent of growth hormone (GH). Fetal development relies on the coordinated actions of a range of hormones, including insulin-like growth factors (IGF), and prolactin (PRL), in the control of differentiation, growth and maturation. In the sheep the abundance peaks for liver IGF-II and PRL receptors occur during late gestation while that for IGF-I receptor occurs at birth. All receptors, with the exception of GH receptor subsequently decrease by age 6 months. It has been proposed that maternal undernutrition during gestation regulates the maturation of the fetal hypothalmic–pituitary–adrenal axis and endocrine sensitivity. Critically, the timing of the nutritional insult may affect the magnitude of reprogramming. Maternal malnutrition during early to mid-gestation (3·2–3·8 MJ/d (60% total metabolisable energy requirements) v. 8·7–9·9 MJ/d (150% total metabolisable energy requirements) between 28 and 80 d of gestation) had no effect on body or liver weight. Nutrient-restricted (NR) fetuses sampled at 80 d (mid-gestation) showed up-regulation of hepatic PRL receptor, but following refeeding the normal gestational rise in PRL and GH receptors did not occur. Hepatic IGF-II receptor was down regulated in NR fetuses at both mid- and late gestation. Conversely, 6-month-old offspring showed no difference in the abundance of either GH receptor or PRL receptor, while IGF-II mRNA was increased. Offspring of ewes malnourished during late gestation (9·1 MJ/d (60% total metabolisable energy requirements) v. 12·7 MJ/d (100% total metabolisable energy requirements) from 110 d of gestation to term) showed reduced abundance of hepatic GH and PRL receptor mRNA. In conclusion, maternal undernutrition during the various stages of gestation reprogrammed the PRL–GH–IGF axis. Nutritional regulation of cytokine receptors may contribute to altered liver function following the onset of GH-dependent growth, which may be important in regulating endocrine adaptations during subsequent periods of nutritional deprivation.

Keywords

Maternal nutritionPRL–GH–IGF axisLiverFetal and neonatal development
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 1 , February 2004 , pp. 127 - 135
Copyright
Copyright © The Nutrition Society 2004

References

Adams, TE (1995) Differential expression of growth hormone receptor messenger RNA from a second promotor. Molecular and Cellular Endocrinology 108, 23–33.CrossRefGoogle Scholar
Barker, D (2002) Fetal programming of coronary heart disease. Trends in Endocrinology and Metabolism 13, 364–368.CrossRefGoogle ScholarPubMed
Barker, DJP, Winter, PD, Osmond, C, Phillips, DIW & Sultan, HY (1995) Weight gain in infancy and cancer of the ovary. Lancet 345, 1087–1088.CrossRefGoogle ScholarPubMed
Bauer, MK, Breier, BH, Harding, JE, Veldhuis, JD & Gluckman, PD (1995) The fetal somatotrophic axis during long term maternal undernutrition in sheep: Evidence for nutritional regulation in utero. Endocrinology 136, 1250–1257.CrossRefGoogle Scholar
Bazan, JF (1990) Structural design and molecular evolution of a cytokine receptor superfamily. Proceedings of the National Academy of Sciences USA 87, 6934–6938.CrossRefGoogle ScholarPubMed
Boyle-Feysot, C, Goffin, V, Edery, M, Binart, N & Kelly, PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocrine Reviews 19, 225–268.CrossRefGoogle Scholar
Brameld, JM, Mostyn, A, Dandrea, J, Stephenson, T, Dawson, J, Buttery, P & Symonds, ME (2000) Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle. Journal of Endocrinology 167, 249–437.CrossRefGoogle ScholarPubMed
Budge, H, Bispham, J, Dandrea, J, Evans, E, Heasman, L, Ingleton, PM, Sullivan, C, Wilson, V, Stephenson, T & Symonds, ME (2000) Effect of maternal nutrition on brown adipose tissue and its prolactin receptor status in the fetal lamb. Pediatric Research 47, 781–786.CrossRefGoogle ScholarPubMed
Cohick, WS & Clemmons, DR (1993) The insulin-like growth factors. Annual Review of Physiology 55, 131–153.CrossRefGoogle ScholarPubMed
Cosman, D (1993) The hematopoietin receptor superfamily. Cytokine 5, 95–106.CrossRefGoogle ScholarPubMed
DeChiara, TM Efstratiadis, A & Robertson, EJ (1990) A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 345, 78–80.CrossRefGoogle ScholarPubMed
Edwards, LJ & McMillen, IC (2001) Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. Journal of Physiology 533, 561–570.CrossRefGoogle ScholarPubMed
El-Brady, OM (1990) Insulin-like growth factor II acts as an autocrine growth and motility factor in human rhabdomyosarcoma tumours. Cell Growth and Differentiation 1, 325–331.Google Scholar
Forhead, AJ, Li, J, Saunders, JC, Dauncey, MJ, Gilmour, RS & Fowden, AL (2000) Control of ovine hepatic growth hormone receptor and insulin-like growth factor I by thyroid hormones in utero. American Journal of Physiology 278, E1166–E1174.Google ScholarPubMed
Fowden, AL, Li, J & Forhead, AJ (1998) Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance?. Proceedings of the Nutrition Society 57, 113–122.CrossRefGoogle ScholarPubMed
Gellersen, B, Bonhoff, A, Hunt, N & Bohnet, HG (1991) Decidual-type prolactin expression by the human myometrium. Endocrinology 129, 158–168.CrossRefGoogle ScholarPubMed
Gluckman, PD, Butler, JH & Elliott, TB (1983) The ontogeny of somatotrophic binding sites in ovine hepatic membranes. Endocrinology 112, 1607–1612.CrossRefGoogle Scholar
Gluckman, PD, Guan, J, Beilharz, EJ, Klempt, ND, Klempt, M, Miller, O, Sirimanne, E, Dragunow, M & Williams, CE (1993) The role of the insulin-like growth factor system in neuronal rescue. Annals of the New York Academy of Sciences 692, 138–148.CrossRefGoogle ScholarPubMed
Gluckman, PD & Harding, JE (1997) The physiology and pathophysiology of intrauterine growth retardation. Hormone Research 48, 11–16.CrossRefGoogle ScholarPubMed
Hankinson, SE, Willett, WC, Michaud, DS, Manson, JE, Golditz, CA, Longcope, C, Rosner, B & Speizer, FE (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. Journal of the National Cancer Institute 91, 629–634.CrossRefGoogle ScholarPubMed
Harding, J (2001) The nutritional basis of the fetal origins of adult disease. International Journal of Epidemiology 30, 15–23.CrossRefGoogle ScholarPubMed
Hawkins, P, Hanson, MA & Matthews, SG (2001) Maternal undernutrition in early gestation alters molecular regulation of the hypothalmic–pituitary–adrenal axis in the ovine fetus. Journal of Neuroendocrinology 13, 855–861.CrossRefGoogle Scholar
Heasman, L, Clarke, L, Firth, K, Stephenson, T & Symonds, ME (1998) Influence of restricted maternal nutrition in early to mid gestation on placental and fetal development at term in sheep. Pediatric Research 44, 546–551.CrossRefGoogle ScholarPubMed
Herzog, CE, Andrassy, RJ & Eftekhari, F (2000) Childhood Cancers: Hepatoblastoma. Oncologist 5, 445–453.CrossRefGoogle ScholarPubMed
Holzenberge, RM, Dupont, J, Ducos, B, Leneuve, P, Geloen, A, Even, PC, Cervera, P & Le Bouc, Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 42, 182–187.CrossRefGoogle Scholar
Hyatt, MA, Bispham, J, Dandrea, J, Walker, DA, Stephenson, T & Symonds, ME (2002a) Maternal nutrient restriction between early to mid-gestation has differential effects on hepatic class 1 cytokine receptor mRNA abundance in mid and late-gestation ovine fetuses. Proceedings of the Nutrition Society 61 121A.Google Scholar
Hyatt, MA, Bispham, J, Dandrea, J, Walker, DA, Symonds, ME & Stephenson, T (2002b) Effect of maternal nutrient restriction during late-gestation on growth hormone (GH) and prolactin (PRL) receptor abundance in neonatal lambs. Proceedings of the Nutrition Society 61 119A.Google Scholar
Hyatt, MA, Bispham, J, Walker, DA, Stephenson, T & Symonds, ME (2003a) Ontogeny of hepatic growth hormone (GH), prolactin (PRL) and insulin-like growth factor-I (IGF-I) receptor mRNA abundance between late-gestation and six months after birth in the lamb. Early Human Development 73 83.Google Scholar
Hyatt, MA, Dandrea, J, Stephenson, T, Walker, DA & Symonds, ME, (2004a) Nutritional programming of insulin-like growth factor-II receptor (IGF-IIR) in ovine fetal liver. Growth Hormone and IGF Research (In the Press).Google Scholar
Hyatt, MA, Gopalakrishnan, G, Bispham, J, Stephenson, T, Walker, DA & Symonds, ME, (2002c) Effect of maternal nutrient restriction during early to mid gestation on hepatic insulin-like growth factor (IGF) mRNA abundance in juvenile sheep. Proceedings of the Physiological Society 547 C63.Google Scholar
Hyatt, MA, Gopalakrishnan, GS, Rhind, SM, Kyle, CE, Brooks, AN, Stephenson, T, Walker, DA & Symonds, ME, (2004b) Effect of maternal nutrient restriction up to 95 days gestation on liver development and cytokine receptor abundance in the adult offspring. Growth Hormone and IGF Research (In the Press).Google Scholar
Hyatt, MA, Stephenson, T, Walker, DA & Symonds, ME, (2004c) Developmental changes in hepatic growth factor receptors as a potential mechanism for explaining neuroblastoma IV-S tumour regression. Growth Hormone and IGF Research (In the Press).Google Scholar
Hyatt, MA, Walker, DA, Stephenson, T & Symonds, ME (2003b) Effect of maternal nutrient restriction during late-gestation on the hepatic insulin-like growth factor (IGF) system in neonatal sheep. Endocrine Abstracts 6 P18Google Scholar
Ihle, JN (1994) The janus kinase family and signalling through members of the cytokine receptor superfamily. Proceedings of the Society for Experimental Biology and Medicine 206, 268–272.CrossRefGoogle ScholarPubMed
Jaffe, CA, Turgeon, DK, Lown, K, Demott-Friberg, R & Watkins, PB (2002) Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans. American Journal of Physiology 283, E1008–E1015.Google ScholarPubMed
Jones, JI & Clemmons, DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocrine Reviews 16, 3–34.Google ScholarPubMed
Khandwala, HM McCutcheon, IE Flyvbjerg, A & Friend, KE (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocrine Reviews 21, 215–244.CrossRefGoogle ScholarPubMed
Kiess, W, Koepf, G & Christiansen, H & Blum, WF (1997) Human neuroblastoma cells use either insulin-like growth factor-I or insulin-like growth factor-II in an autocrine pathway via the IGF-I receptor: variability of IGF, IGF binding protein (IGFBP) and IGF receptor gene expression and IGF and IGFBP secretion in human neuroblastoma cells in relation to cellular proliferation. Regulatory Peptide 72, 19–29.CrossRefGoogle ScholarPubMed
Kind, KL, Owens, JA, Robinson, JS, Quinn, KJ, Grant, PA, Walton, PE, Gilmour, RS & Owens, PC (1995) Effect of restriction of placental growth on expression of IGFs in fetal sheep – relationships to fetal growth, circulating IGFs and binding-proteins. Journal of Endocrinology 146, 23–24.CrossRefGoogle ScholarPubMed
Klempt, M, Bingham, B, Breier, BH, Baumbach, WR & Gluckman, PD (1993) Tissue distribution and ontogeny of growth hormone receptor messenger ribonucleic acid and ligand binding to hepatic tissue in the midgestation sheep fetus. Endocrinology 132, 1071–1077.CrossRefGoogle ScholarPubMed
Lacroix, M-C Devinoy, E, Cassy, S, Servely, J-L Vidaud, M & Kann, G (1999) Expression of growth hormone and its receptor in the early placental and feto-maternal environment during early pregnancy in sheep. Endocrinology 140, 5587–5597.CrossRefGoogle ScholarPubMed
Li, J, Gilmour, RS, Saunders, JC, Dauncey, MJ & Fowden, AL (1999) Activation of the adult mode of the ovine growth hormone receptor gene expression by cortisol during late fetal development. FASEB Journal 13, 545–552.CrossRefGoogle ScholarPubMed
Li, J, Owens, J, Owens, P, Saunders, J, Fowden, A & Gilmour, R (1996) The ontogeny of hepatic growth hormone receptor and insulin-like growth factor I gene expression in the sheep fetus during late gestation: developmental regulation by cortisol. Endocrinology 137, 1650–1657.CrossRefGoogle ScholarPubMed
Liu, JP, Baker, J, Perkins, AS, Robertson, EJ & Efstratiadis, A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75, 59–72.Google ScholarPubMed
Meyer, DJ, Stephenson, EW, Johnson, L, Cochran, BH & Schwartz, J (1993) The serum response element can mediate induction of c-fos by growth hormone. Proceedings of the National Academy of Sciences USA 90, 6721–6725.CrossRefGoogle ScholarPubMed
Newsome, CA, Shiell, AW, Fall, CHD, Phillips, DIW, Shier, R & Law, CM (2003) Is birth weight related to later glucose and insulin metabolism?. Diabetic Medicine 20, 339–348.CrossRefGoogle ScholarPubMed
O'Dell, SD & Day, INM (1998) Molecules in focus: Insulin-like growth factor II (IGF-II). International Journal of Biochemistry and Cell Biology 30, 767–771.CrossRefGoogle Scholar
O'sullivan, DC, Szestak, TAM & Pell, JM (2002) Regulation of hepatic insulin-like growth factor I leader exon usage in lambs: Effect of immunization against growth hormone-releasing factor and subsequent growth hormone treatment. Journal of Animal Sciences 80, 1074–1082.CrossRefGoogle ScholarPubMed
Owens, JA (1991) Endocrine and substrate control of fetal growth: placental and maternal influences and insulin-like growth factors. Reproduction Fertility and Development 3, 507–517.CrossRefGoogle ScholarPubMed
Owens, JA, Kind, KL, Carbone, F, Robinson, JS & Owens, PC (1994) Circulating insulin-like growth factors-I and -II and substrates in fetal sheep following restriction of placental growth. Journal of Endocrinology 140, 5–13.CrossRefGoogle ScholarPubMed
Ozanne, S & Hales, C (2002) Early programming of glucose and insulin metabolism. Trends in Endocrinology and Metabolism 13, 368–373.CrossRefGoogle Scholar
Phillips, ID, Fielke, SL, Young, IR & McMillen, IC (1996) The relative roles of the hypothalamus and cortisol in the control of prolactin gene expression in the anterior pituitary of the sheep fetus. Journal of Neuroendocrinology 8, 929–933.CrossRefGoogle ScholarPubMed
Reynolds, TS, Stevenson, KR & Wathes, DC (1997) Pregnancy-specific alterations in the expression of the insulin-like growth factor system during early placental development in the ewe. Endocrinology 138, 886–897.CrossRefGoogle ScholarPubMed
Rother, KI & Accili, D (2000) Role of insulin receptors and IGF in growth and development. Pediatric Nephrology 14, 558–561.CrossRefGoogle ScholarPubMed
Sjogren, K, Liu, J-L, Blad, K, Skrtic, S, Vidal, O, Wallenius, V, LeRoith, D Tornell, J, Isaksson, OGP, Jansson, J-O & Ohlsson, C (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proceedings of the National Academy of Sciences USA 96, 7088–7092.CrossRefGoogle Scholar
Symonds, M, Gopalakrishnan, G, Bispham, J, Pearce, S, Dandrea, J, Mostyn, A, Ramsay, M & Stephenson, T (2003) Maternal nutrient restriction during placental growth, programming of fetal adiposity and juvenile blood pressure control. Archives of Physiology and Biochemistry 111, 45–52.CrossRefGoogle ScholarPubMed
Symonds, ME, Mostyn, A & Stephenson, T (2001) Cytokines and cytokine receptors in fetal growth and development. Biochemical Society Transactions 29, 33–37.CrossRefGoogle ScholarPubMed
Vatten, LJ, Maehle, BO Lund Nilsen, TI, Tretli, S, Hsieh, CC, Trichopoulos, D & Stuver, SO (2002) Birth weight as a predictor of breast cancer: a case-control study in Norway. British journal of Cancer 86, 89–91.CrossRefGoogle ScholarPubMed
Wang, ZQ, Fung, MR, Barlow, DP & Wagner, EF (1994) Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. Nature 272, 464–467.CrossRefGoogle Scholar
Whorwood, CB, Firth, KM, Budge, H & Symonds, ME (2001) Maternal undernutrition during early to midgestation programs tissue-specific alterations in the expression of the glucocorticoid receptor, 11beta-hydroxysteroid dehydrogenase isoforms, and type 1 angiotensin II receptor in neonatal sheep. Endocrinology 142, 2854–2864.CrossRefGoogle ScholarPubMed
Zhou, Y, Xu, BC, Maheshwari, HG, He, L, Reed, M, Lozykowski, M, Okada, S, Cataldo, L, Coschigamo, K, Wagner, TE, Baumann, G & Kopchick, JJ (1997) A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proceedings of the National Academy of Sciences USA 94, 13215–13220.CrossRefGoogle ScholarPubMed
Zogopoulos, G, Figueiredo, R, Jenab, A, Ali, Z, Lefebvre, Y & Goodyer, CG (1996) Expression of exon 3-retaining and -deleted human growth hormone receptor messenger ribonucleic acid isoforms during development. Journal of Clinical Endocrinology and Metabolism 81, 775–782.Google ScholarPubMed