Abstract
We investigated the influence of maternal nutritional enhancement during the second half of gestation on prolactin receptor (PRLR) abundance in fetal brown adipose tissue (BAT) and liver close to term (i.e. 141–144 d gestation). Ewes were provided with 100% (i.e. control;n = 8) or 150% (i.e. well-fed;n = 7) of their metabolic requirements from 80 to 144 d gestation. Crude plasma membranes were prepared from fetal BAT and hepatic tissue, and individual molecular weight isoforms for the long and short forms of the PRLR were detected by immunoblotting. Mitochondrial preparations were prepared from BAT to measure the amount of the BAT-specific mitochondrial uncoupling protein-1 and its thermogenic activity (i.e. guanosine 5′-diphosphate binding). Fetuses sampled from well-fed ewes were heavier (controls, 3927 ± 196 g; well-fed, 4783 ± 219 g;p = 0.01) but possessed less BAT per kilogram body weight (controls, 5.92 ± 0.43 g/kg; well-fed, 3.85 ± 0.19 g/kg;p = 0.001), which had a greater uncoupling protein-1 abundance (controls, 56 ± 5% of reference; well-fed, 78 ± 9% of reference;p < 0.01) and higher thermogenic activity (controls, 157 ± 41 pmol guanosine 5′-diphosphate per milligram mitochondrial protein; well-fed, 352 ± 36 pmol guanosine 5′-diphosphate per milligram mitochondrial protein;p < 0.01) than controls. Multiple isoforms of the long and short forms of the PRLR were detected in all tissues. BAT from well-fed fetuses had a higher abundance of the 15-kD isoform of the long form of the PRLR (controls, 1.6 ± 0.4 densitometric units; well-fed, 16.3 ± 2.0 densitometric units;p < 0.001). This isoform was not detected in hepatic tissue. Maternal nutrient intake had no effect on any other isoforms of the PRLR in BAT or liver. In conclusion, increasing the quantity of feed provided in late gestation acts to promote fetal weight and BAT maturation, the combination of which will enhance neonatal viability.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BAT:
-
brown adipose tissue
- GDP:
-
guanosine 5′-diphosphate
- JAK:
-
Janus kinase
- ME:
-
metabolizable energy
- PRLR:
-
prolactin receptor
- PRLR-1:
-
long form of the prolactin receptor
- PRLR-2:
-
short form of the prolactin receptor
- STAT:
-
signal transducers and activators of transcription
- UCP1:
-
uncoupling protein-1
References
Lucas A, Baker BA, Gole TJ 1990 Plasma prolactin and clinical outcome in preterm fetuses. Arch Dis Child 65: 977–983
Merei JJ, Rao A, Clarke IJ, McMillen IC 1993 Proopiomelanocortin, prolactin and growth hormone messenger ribonucleic acid levels in the fetal sheep pituitary during late gestation. Acta Endocrinol 129: 263–267
Gluckman PD, Grumbach MM, Kaplan SL 1981 The neuroendocrine regulation and function of growth hormone and prolactin in the mammalian fetus. Endocr Rev 2: 363–395
Harding JE, Jones CT, Robinson JS 1985 Studies on experimental growth retardation in sheep: the effects of a small placenta in restricting transport to and growth of the fetus. J Dev Physiol 7: 427–442
Royster M, Driscoll P, Kelly PA, Freemark M 1995 The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand binding activity and induction in late gestation. Endocrinology 136: 3892–3900
Schuler LA, Nagel RJ, Gao J, Horseman ND, Kessler MA 1997 Prolactin receptor heterogeneity in bovine fetal and maternal tissues. Endocrinology 138: 3187–3194
Phillips ID, Anthony RV, Butler TG, Ross JT, McMillen IC 1997 Hepatic prolactin receptor gene expression increases in the sheep fetus before birth and after cortisol infusion. Endocrinology 138: 1351–1354
Phillips ID, Anthony RV, Houghton DC, McMillen IC 1999 The regulation of prolactin receptor messenger ribonucleic acid levels in the sheep liver before birth: relative roles of the fetal hypothalamus, cortisol, and external photoperiod. Endocrinology 140: 1966–1971
Symonds ME, Phillips ID, Anthony RV, Owens JA, McMillen IC 1998 Prolactin receptor gene expression and foetal adipose tissue. J Neuroendocrinol 10: 885–890
Casteilla L, Forest C, Robelin J, Ricquier D, Lombert A, Ailhand G 1987 Characterization of mitochondrial-uncoupling protein in bovine fetus and newborn calf. Am J Physiol 252: E627–E636
Clarke L, Heasman L, Firth K, Symonds ME 1997 Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs. Am J Physiol 272: R1931–R1939
Mellor DJ, Cockburn F 1986 A comparison of energy metabolism in the new-born infant, piglet and lamb. Q J Exp Physiol 71: 361–379
Symonds ME, Bryant MJ, Clarke L, Darby CJ, Lomax MA 1992 Effect of maternal cold exposure on brown adipose tissue and thermogenesis in the neonatal lamb. J Physiol Lond 455: 487–502
Jahnukainen T, Lindqvist A, Jalonen J, Kero P, Valimaki I 1996 Reactivity of skin blood flow and heart rate to thermal stimulation in infants during the first postnatal days and after two-month follow-up. Acta Paediatr 85: 733–738
Piper JM, Field NT, Higby K, Elliott BD, Langer O 1996 Maternal-fetal glucose metabolism and fetal growth retardation: is there an association?. J Reprod Med 41: 761–766
Barker DJP 1994 Mothers, Babies and Disease in Later Life. BMJ Publishing Group, London, pp 37–52
Agricultural and Food Research Council. 1992 Technical Committee on Responses to Nutrients. Report No. 9, CAB International, Wallingford, UK, pp 812–815
Rothwell J, Stock MJ, Sudera DK 1985 β-Adrenoreceptors in rat brown adipose tissue: proportions of β1-, β2-subtypes. Am J Physiol 248: E397–E402
Nevalainen M, Valve EM, Ingleton PM, Harkonen PL 1996 Expression and hormone regulation of prolactin receptors in rat dorsal and lateral prostate. Endocrinology 137: 3078–3088
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ 1951 Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275
Tortonese DJ, Brooks J, Ingleton PM, McNeilly AS 1998 Detection of prolactin receptor gene expression in the sheep pituitary gland and visualization of the specific translation of the signal in gonadotrophs. Endocrinology 139: 5215–5233
Schermer SJ, Bird JA, Lomax MA, Shepherd DAL, Symonds ME 1996 Effect of fetal thyroidectomy on brown adipose tissue and thermoregulation in newborn lambs. Reprod Fertil Dev 8: 995–1002
Clarke L, Darby CJ, Lomax MA, Symonds ME 1994 Effect of ambient temperature during 1st day of life on thermoregulation in lambs delivered by cesarean section. J Appl Physiol 76: 1481–1488
Gong DW, He Y, Karas M, Reitman M 1997 Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, β3-adrenergic agonists, and leptin. J Biol Chem 272: 24129–24132
Choy VJ, Nixon AJ, Pearson AJ 1997 Distribution of prolactin receptor immunoreactivity in ovine skin and changes during the wool follicle growth cycle. J Endocrinol 155: 265–275
Shirota M, Banville D, Ali S, Jolicoeur C, Boutin JM, Edery M, Djiane J, Kelly PA 1990 Expression of two forms of prolactin receptor in rat ovary and liver. Mol Endocrinol 4: 1136–1143
Gertler A, Petridou B, Kriwi G, Dijane J 1993 Interaction of lactogenic hormones with purified recombinant extracellular domain of the rabbit prolactin receptor expressed in cells. FEBS Lett 319: 277–281
Hooper KP, Padmanabhan R, Ebner KE 1993 Expression of the extracellular domain of the rat liver receptor and its interaction with ovine prolactin. J Biol Chem 268: 22347–22352
Chan E, Swaminathan R 1980 Role of prolactin in lactation-induced changes in brown adipose tissue. Am J Physiol 258: R51–R56
Horseman ND, Yu-Lee L-Y 1994 Transcriptional regulation by the helix bundle proteins: growth hormone, prolactin, and hematopoietic cytokines. Endocr Rev 15: 627–649
DaSilva L, Rui H, Erwin RA, Howard OMZ, Kriken RA, Malabarba MG, Hackett RH, Larner AC, Farrar WL 1996 Prolactin recruits Stat1, Stat3 and Stat5 independent of conserved receptor tyrosines Tyr402, Tyr479, Tyr515 and Tyr580. Mol Cell Endocrinol 117: 131–140
Kelly PA, Djiane J, Postel-Vinay MC, Edery M 1991 The prolactin/growth hormone receptor family. Endocr Rev 12: 235–251
Friedman JM, Halaas JL 1998 Leptin and the regulation of body weight in mammals. Nature 763: 770
Pelleymounter MA, Cullen KS, Baker MB, Hercht R, Winters D, Boone T, Collins F 1995 Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 543–546
Ghilardi N, Ziegler S, Wiestner A, Stoffel R, Heim MH, Skoda RC 1996 Defective STAT signaling by the leptin receptor in diabetic mice. Proc Natl Acad Sci USA 93: 6321–6325
Kohsaka A, Watanobe H, Kakizaki Y, Habu S, Suda T 1999 A significant role of leptin in the generation of steroid-induced luteinizing hormone and prolactin surges in female rats. Biochem Biophys Res Commun 254: 578–581
Symonds ME, Stephenson T 1999 Maternal nutrient restriction and endocrine programming of fetal adipose tissue development. Biochem Soc Trans 27: 97–103
Soothill PW, Nicolaides KH, Campbell S 1987 Prenatal asphyxia, hyperlacticaemia, hypoglycaemia, and erythroblastosis in growth retarded fetuses. BMJ 294: 1051–1053
Owens JA, Owens PC, Robinson JS 1995 Experimental restriction of growth. In: Hanson MA, Spencer JAD, Rodeck CH (eds) The Fetus and Neonate. Volume Three. Growth. Cambridge University Press, Cambridge, pp 139–175
Simonetta G, Rourke AK, Owens JA, Robinson JS, McMillen IC 1997 Impact of fetal growth restriction on the development of the sympathoadrenal system. Pediatr Res 42: 805–811
Stevens D, Alexander G, Bell AW 1990 Effects of prolonged glucose infusion into fetal sheep on body growth, fat deposition and gestation. J Dev Physiol 13: 277–281
Molina RD, Meschia G, Battaglia FC, Hay WW 1991 Gestational maturation of placental transfer of glucose. Am J Physiol 261: R697–R704
Faichney GJ, White GA 1987 Effect of maternal nutritional status on fetal and placental growth and on fetal urea synthesis. Aust J Biol Sci 40: 365–377
Tyzbir RS 1984 Altered brown adipose tissue mitochondrial function in neonates born to rats overfed foods of various protein content. J Nutr 114: 234–237
Rothwell NJ, Stock MJ 1981 Influence of noradrenaline on blood flow to brown adipose tissue in rats exhibiting diet-induced thermogenesis. Pflugers Arch 389: 237–242
Rohlfs EM, Daniel KW, Premont RT, Kozak LP, Collins S 1995 Regulation of uncoupling protein gene (UCP) by β1-, β2-, and β3-adrenergic receptor subtypes in immortalized brown adipose cell lines. J Biol Chem 270: 10723–10732
Largercrantz H, Slotkin TA 1985 The “stress” of being born. Sci Am 254: 92–102
Cohen WR, Piasecki GJ, Cohn HE, Jackson BT 1982 Plasma catecholamines during hypoxemia in fetal lamb. Am J Physiol R250–R255
Bassett JM, Symonds ME 1998 β2-Agonist ritodrine, unlike natural catecholamines, activates thermogenesis prematurely in utero in fetal sheep. Am J Physiol 275: R112–R119
Bassett JM, Hanson C 1998 Catecholamines inhibit growth in fetal lambs in the absence of hypoxemia. Am J Physiol 274: R1536–R1545
Casteilla L, Champigny O, Bouilland F, Robelin J, Ricquier D 1989 Sequential changes in the expression of mitochondrial protein mRNA during development of brown adipose tissue. Biochem J 257: 665–671
Bianco AC, Silva JE 1987 Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation. Am J Physiol 253: E255–E263
Rabelo R, Reyes C, Schifman A, Silva JE 1996 Interactions among receptors, thyroid responsive elements, and ligands in the regulation of the rat uncoupling protein gene expression by thyroid hormone. Endocrinology 137: 3478–3487
Fraser M, Liggins GC 1988 Thyroid hormone kinetics during pregnancy in the ovine fetus. J Dev Physiol 10: 461–467
Author information
Authors and Affiliations
Additional information
Supported in part by the Royal Society and Special Trustees for University of Nottingham Hospitals. L. Heasman and J. Dandrea were both supported by a Ministry of Agriculture, Fisheries and Food studentships.
Rights and permissions
About this article
Cite this article
Budge, H., Bispham, J., Dandrea, J. et al. Effect of Maternal Nutrition on Brown Adipose Tissue and Its Prolactin Receptor Status in the Fetal Lamb. Pediatr Res 47, 781–786 (2000). https://doi.org/10.1203/00006450-200006000-00017
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-200006000-00017
This article is cited by
-
Parenteral administration of twin-bearing ewes with L-arginine enhances the birth weight and brown fat stores in sheep
SpringerPlus (2013)
-
Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep
Amino Acids (2013)
-
Adipose tissue and fetal programming
Diabetologia (2012)
