Skip to main content
SpringerLink
Log in

Mammary Specific Transgenic Over-expression of Insulin-like Growth Factor-I (IGF-I) Increases Pig Milk IGF-I and IGF Binding Proteins, with no Effect on Milk Composition or Yield

  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

IGF-I regulates lactation by stimulating mammary mitogenesis, inhibiting apoptosis, and partially mediating the effects of growth hormone on lactogenesis. Herein, lactation performance during first and second parity was assessed in transgenic swine (TG) that over-expressed human IGF-I in milk under the control of the bovine α-lactalbumin promoter, regulatory regions and signal peptide coding sequence. Milk samples were collected throughout lactation (farrowing to d24) from TG sows and non-transgenic littermates (CON) and IGF-I, IGF-II, and IGFBP determined. Colostral (<24 h postpartum) IGF-I content was 26-fold greater (p < 0.001) in TG sows (949 ± 107 μg/L; range 228–1600 μg/L) than CON (36 ± 17.8 μg/L) and was 50- to 90-fold greater (p < 0.001) in mature milk (d2-24 postpartum). There was no effect of parity on milk IGF-I content. Milk IGF-II concentration was unaffected by IGF-I over-expression. Low molecular weight IGFBP (IGFBP-2 and -5) in the milk of TG sows were higher (p = 0.02) than CON in the early postpartum period, but did not differ in mature milk. Milk yield, determined by weigh-suckle-weigh, was similar in TG and CON as was litter weight gain. Milk nutrient composition was not significantly affected by IGF over-expression. Thus, mammary specific transgenic over-expression of IGF-I significantly increased milk IGF-I and IGFBP content, but did not impact lactation performance in swine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • GJ Allan J Beattie DJ Flint (2004) ArticleTitleThe role of IGFBP-5 in mammary gland development and involution Domest Anim Endocrinol 27 25–266 Occurrence Handle10.1016/j.domaniend.2004.06.009 Occurrence Handle15158532

    Article  PubMed  Google Scholar 

  • JD Armstrong MT Coffey KL Esbenshade RM Campbell EP Heimel (1994) ArticleTitleConcentrations of hormones and metabolites, estimates of metabolism, performance, and reproductive performance of sows actively immunized against growth hormone-releasing factor J Anim Sci 72 1570–1577 Occurrence Handle8071182

    PubMed  Google Scholar 

  • I Barash A Faerman M Richenstein R Kari G-M Damary M Shani MJ Bissell (1999) ArticleTitleIn vivo and in vitro expression of human serum albumin genomic sequences in mammary epithelial cells with β-lactoglobulin and whey acidic protein promoters Molec Repro Devel 52 241–252 Occurrence Handle10.1002/(SICI)1098-2795(199903)52:3<241::AID-MRD1>3.0.CO;2-X

    Article  Google Scholar 

  • R Baserga R Rubin (1993) ArticleTitleCell cycle and growth control Crit Rev Eukaryot Gene Exp. 3 47–61

    Google Scholar 

  • GT Bleck BR White DJ Miller MB Wheeler (1998) ArticleTitleProduction of bovine α-lactalbumin in the milk of transgenic pigs J Anim Sci 76 3072–3078 Occurrence Handle9928612

    PubMed  Google Scholar 

  • DG Burrin TJ Wester TA Davis S Amick JP Heath (1996) ArticleTitleOrally administered insulin-like growth factor-I increases intestinal mucosal growth in formula-fed neonatal pigs Am J Physiol 270 R1085–R1091 Occurrence Handle8928910

    PubMed  Google Scholar 

  • DG Burrin ML Fiorotto DL Hadsell (1999) ArticleTitleTransgenic hypersecretion of des(1–3) human insulin-like growth factor I in mouse milk has limited effects on the gastrointestinal tract in suckling pups J Nutr 129 51–56 Occurrence Handle9915875

    PubMed  Google Scholar 

  • GL Cromwell TS Stahly LA Edgerton HJ Monegue TW Burnell BC Schenck BR Schricker (1992) ArticleTitleRecombinant porcine somatotropin for sows during late gestation and throught lactation J Anim Sci 70 1404–1416 Occurrence Handle1526909

    PubMed  Google Scholar 

  • SM Donovan LK McNeil R Jimenez-Flores J Odle (1994) ArticleTitleInsulin-like growth factors and IGF binding proteins in porcine serum and milk throughout lactation Pediatr Res 36 159–168 Occurrence Handle7970929

    PubMed  Google Scholar 

  • SM Donovan J Odle (1994) Growth factors in milk as mediators of infant development RE Olson DM Bier DB McCormick (Eds) Annual Reviews of Nutrition NumberInSeriesVol. 14 Annual Reviews, Inc Palo Alto, CA 147–167

    Google Scholar 

  • SM Donovan JC-J Chao RT Zijlstra J Odle (1997) ArticleTitleOrally administered iodinated recombinant human insulin-like growth factor-I (125I-IGF-I) is poorly absorbed by neonatal piglets J Pediatr Gastroenterol Nutr 24 174–182 Occurrence Handle10.1097/00005176-199702000-00011 Occurrence Handle9106104

    Article  PubMed  Google Scholar 

  • SM Donovan MH Monaco GT Bleck JB Cook MS Noble WL Hurley MB Wheeler (2001) ArticleTitleTransgenic over-expression of bovine α-lactalbumin and human insulin-like growth factor in porcine mammary gland J Dairy Sci 84 IssueIDE. Suppl. E216–E222

    Google Scholar 

  • MW Elmlinger R Grund M Buck HA Wollmann N Feist MM Weber CP Speer MB Ranke (1999) ArticleTitleLimited proteolysis of the IGF binding protein-2 (IGFBP-2) by a specific serine protease activity in early breast milk Pediatr Res 46 76–81 Occurrence Handle10400138

    PubMed  Google Scholar 

  • TD Etherton DE Bauman (1998) ArticleTitleBiology of somatotropin in growth and lactation of domestic animals Physio Rev 78 745–761

    Google Scholar 

  • DJ Flint E Tonner GJ Allan (2000) ArticleTitleInsulin-like growth factor binding proteins: IGF-dependent and -independent effects in the mammary gland J Mamm Gland Biol 5 65–73 Occurrence Handle10.1023/A:1009567316520

    Article  Google Scholar 

  • MI Gallego N Binart GW Robinson R Okagaki KT Conschigano J Perry JJ Kopchick T Oka PA Kelly L Henninghausen (2001) ArticleTitleProlactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects Dev Biol 220 163–175 Occurrence Handle10.1006/dbio.2000.9961

    Article  Google Scholar 

  • VY Godbole ML Grundleger TA Pasquine SW Thenen (1981) ArticleTitleComposition of rat milk from day 5 to 29 of lactation and milk intake of lean and preobese Zucker pups J Nutr 111 480–487 Occurrence Handle7193715

    PubMed  Google Scholar 

  • DL Hadsell SG Bonnette AV Lee (2002) ArticleTitleGenetic manipulation of the IGF-I axis to regulate mammary gland development and function J Dairy Sci 85 365–377 Occurrence Handle11913696

    PubMed  Google Scholar 

  • DL Hadsell NM Greenberg JM Fligger CR Baumrucker JM Rosen (1996) ArticleTitleTargeted expression of des(1–3) human insulin-like growth factor I in transgenic mice influences mammary gland development and IGF-binding protein expression Endocrinol 137 321–330 Occurrence Handle10.1210/en.137.1.321

    Article  Google Scholar 

  • M Harkins RD Boyd DE Bauman (1989) ArticleTitleEffect of recombinant porcine somatotropin on lactational performance and metabolite patterns in sows and growth of nursing pigs J Anim Sci 67 1997–2008 Occurrence Handle2793622

    PubMed  Google Scholar 

  • M Hirabayashi R-I Takahashi K Ito N Kashiwazaki M Hirao K Hirasawa S Hochi M Ueda (2001) ArticleTitleA comparative study on the integration of exogenous DNA into mouse, rat, rabbit and pig genomes Exp Anim 50 125–131 Occurrence Handle10.1538/expanim.50.125 Occurrence Handle11381615

    Article  PubMed  Google Scholar 

  • B Hogan F Constantini E Lacy (1986) Manipulating the mouse embryo: A laboratory Manual Cold Spring Harbor Laboratory Cold Spring Harbor, NY

    Google Scholar 

  • Holly JMP, Perks CM and Stewart CEH (2000) Overview of insulin-like growth factor physiology. Growth Horm IGF Res, Suppl A:S8–S9.

  • VM Houle EA Schroeder J Odle SM Donovan (1997) ArticleTitleSmall intestinal disaccharidase activity and ileal villus height are increased in piglets consuming formula containing recombinant human insulin-like growth factor-I Pediatr Res 42 78–86 Occurrence Handle9212041

    PubMed  Google Scholar 

  • VM Houle SC Laswell GG Freund MA Dudley SM Donovan (2000) ArticleTitleInvestigation of three doses of oral insulin-like growth factor-I on jejunal lactase phlorizin hydrolase activity and gene expression and enterocyte proliferation and migration in piglets Pediatr Res 48 497–503 Occurrence Handle11004241

    PubMed  Google Scholar 

  • FR Jevons (1964) ArticleTitleDetection of non-reducing carbohydrate with orcinol in phosphoric acid J Chromatogr 16 252–253 Occurrence Handle10.1016/S0021-9673(01)82475-4 Occurrence Handle14226357

    Article  PubMed  Google Scholar 

  • JI Jones DR Clemmons (1995) ArticleTitleInsulin-like growth factors and their binding proteins: Biological actions Endocrine Rev 16 3–34 Occurrence Handle10.1210/er.16.1.3

    Article  Google Scholar 

  • CY Lee FW Bazer FA Simmen (1993) ArticleTitleExpression of components of the insulin-like growth factor system in pig mammary glands and serum during pregnancy and pseudopregnancy: Effects of oestrogen J Endocrinol 137 473–483 Occurrence Handle7690391

    PubMed  Google Scholar 

  • E Marshman CH Streuli (2002) ArticleTitleInsulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function Breast Cancer Res 4 231–239 Occurrence Handle10.1186/bcr535 Occurrence Handle12473169

    Article  PubMed  Google Scholar 

  • S Neuenschwander A Schawartz TL Wood CT Roberts SuffixJr. L Henninghausen (1996) ArticleTitleInvolution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model J Clin Invest 97 2225–2232 Occurrence Handle8636401

    PubMed  Google Scholar 

  • MS Noble S Rodriguez-Zas JB Cook GT Bleck WL Hurley MB Wheeler (2003) ArticleTitleLactational performance of first-parity transgenic gilts expressing bovine alpha-lactalbumin in their milk J Anim Sci 80 1090–1096

    Google Scholar 

  • Y Oh HL Müller DY Lee PJ Fielder RG Rosenfeld (1993a) ArticleTitleCharacterization of the affinities of insulin-like growth factor (IGF)-binding proteins 1–4 for IGF-I, IGF-II, IGF-/insulin hybrid, and IGF-I analogs Endocrinology 132 1337–1344 Occurrence Handle10.1210/en.132.3.1337

    Article  Google Scholar 

  • Y Oh H Müller L Neely G Lamson RG Rosenfeld (1993b) ArticleTitleNew concepts in insulin-like growth factor receptor physiology Growth Reg 3 113–123

    Google Scholar 

  • GL Peterson (1977) ArticleTitleA simplification of the protein assay method of Lowry et al which is more generally applicable Anal Biochem 83 346–356 Occurrence Handle10.1016/0003-2697(77)90043-4 Occurrence Handle603028

    Article  PubMed  Google Scholar 

  • CG Prosser SR Davis VC Farr G Moore PD Gluckman (1994) ArticleTitleEffects of close-arterial (external pudic) infusion of insulin-like growth factor-II on milk yield and mammary blood flow in lactating goats J Endocrinol 142 93–99 Occurrence Handle7964289

    PubMed  Google Scholar 

  • H Salvo-Garrido S Travella LJ Bilham WA Harwood JW Snape (2004) ArticleTitleThe distribution of transgene insertion sites in barley determined by physical and genetic mapping Genetics 167 1371–1379 Occurrence Handle10.1534/genetics.103.023747 Occurrence Handle15280249

    Article  PubMed  Google Scholar 

  • DA Schober FA Simmen DL Hadsell CR Baumrucker (1990) ArticleTitlePerinatal expression of type I IGF receptors in porcine intestine Endocrinology 126 1125–1132 Occurrence Handle2153520

    PubMed  Google Scholar 

  • FS Simmen KY Whang RCM Simmen GA Peterson MD Bishop KM Irvin (1990) ArticleTitleLactational variation and relationship to postnatal growth insulin-like growth factor-I in mammary secretions from genetically diverse sows Domest Anim Endocrinol 7 199–206 Occurrence Handle10.1016/0739-7240(90)90026-V Occurrence Handle2369820

    Article  PubMed  Google Scholar 

  • HY Su WTK Cheng (2004) ArticleTitleIncreased milk yield in transgenic mice expressing insulin-like growth factor-1 Anim Biotechnol 15 9–19 Occurrence Handle10.1081/ABIO-120027521 Occurrence Handle15248597

    Article  PubMed  Google Scholar 

  • MS Toner RH King FR Dunshea H Dove CS Atwood (1996) ArticleTitleThe effect of exogenous somatotropin on lactation performance of first litter sows J Anim Sci 74 167–172 Occurrence Handle8778096

    PubMed  Google Scholar 

  • E Tonner C Barber MT Travers A Logan DJ Flint (1997) ArticleTitleHormonal control of insulin-like growth factor-binding protein-5 production in the involuting mammary gland of the rat Endocrinology 138 5101–5107 Occurrence Handle10.1210/en.138.12.5101 Occurrence Handle9389489

    Article  PubMed  Google Scholar 

  • E Tonner C Barber GJ Allan J Beattie J Webster CBA Whitelaw DJ Flint (2002) ArticleTitleInsulin-like growth factor-5 (IGFBP-5) induces premature cell death in mammary glands of transgenic mice Development 129 4547–4557 Occurrence Handle12223411

    PubMed  Google Scholar 

  • PD Walden W Ruan K Feldman DL Kleinbert (1998) ArticleTitleEvidence that the mammary fat pad mediates the action of growth hormone in mammary gland development Endocrinology 129 659–662 Occurrence Handle10.1210/en.139.2.659

    Article  Google Scholar 

  • NL Warman KM Rasmussen (1983) ArticleTitleEffects of malnutrition during reproductive cycle on nutritional status and lactational performance of rat dams Nutr Res 3 527–545

    Google Scholar 

  • MS Weber PL Boyle BA Corl EA Wong FC Gwazdauskas RM Aker (1998) ArticleTitleExpression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice Endocrine 8 251–259 Occurrence Handle10.1385/ENDO:8:3:251 Occurrence Handle9741830

    Article  PubMed  Google Scholar 

  • E Wolf PM Jehle MM Weber H Sauerwein A Daxenberger BH Breier U Besebfelder L Frenyo G Brem (1997) ArticleTitleHuman insulin-like growth factor I (IGF-I) produced in the mammary glands of transgenic rabbits: yield, receptor binding, mitogenic activity, and effects on IGF-binding proteins Endocrinology 138 307–313 Occurrence Handle10.1210/en.138.1.307 Occurrence Handle8977418

    Article  PubMed  Google Scholar 

  • X Zhao TG Unterman SM Donovan (1995) ArticleTitleHuman growth hormone but not human insulin-like growth factor-I enhances recovery from neonatal malnutrition in rats J Nutr 125 1316–1327 Occurrence Handle7537807

    PubMed  Google Scholar 

  • N Zinovieva C Lassnig D Schams U Besebfelder E Wolf S Muller L Frenyo J Seregi M Muller G Brem (1998) ArticleTitleStable production of human insulin-like growth factor 1 (IGF-1) in the milk of hemi- and homozygous transgenic rabbits over several generations Transgenic Res 7 437–447 Occurrence Handle10.1023/A:1008831028620 Occurrence Handle10341452

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, 61801, USA

    Marcia H. Monaco & Sharon M. Donovan

  2. Department of Animal Sciences, University of Illinois, Urbana, IL, 61801, USA

    Derek E. Gronlund, Gregory T. Bleck, Walter L. Hurley & Matthew B. Wheeler

  3. Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL, 61801, USA

    Matthew B. Wheeler

Authors
  1. Marcia H. Monaco
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derek E. Gronlund
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gregory T. Bleck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Walter L. Hurley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew B. Wheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sharon M. Donovan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharon M. Donovan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Monaco, M.H., Gronlund, D.E., Bleck, G.T. et al. Mammary Specific Transgenic Over-expression of Insulin-like Growth Factor-I (IGF-I) Increases Pig Milk IGF-I and IGF Binding Proteins, with no Effect on Milk Composition or Yield. Transgenic Res 14, 761–773 (2005). https://doi.org/10.1007/s11248-005-7219-8

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11248-005-7219-8

Keywords

Search

Navigation