Nutritional and Tissue Specificity of IGF-I and IGFBP-2 Gene Expression in Growing Chickens* - A Review -

Transcription

1 747 Nutritionl nd Tissue Speifiity of IGF-I nd IGFBP-2 Gene Expression in Growing Chikens* - A Review - K. Kit**, K. Ngo nd J. Okumur 1 Grdute Shool of Biogriulturl Sienes, Ngoy University, Ngoy , Jpn ABSTRACT : Nutritionl regultion of gene expression ssoited with growth nd feeding ehvior in vin speies n eome n importnt tehnique to improve poultry prodution ording to the supply of nutrients in the diet. Insulin-like growth ftor-i (IGF-I) found in hikens hs een hrterized to e 7 mino id polypeptide nd plys n importnt role in growth nd metolism. Although it is een well known tht IGF-I is highly ssoited with emryoni development nd post-hthing growth, hnges in the distriution of IGF-I gene expression throughout erly- to lte-emryogenesis hve not een studied so fr. We reveled tht the developmentl pttern of IGF-I gene expression during emryogenesis differed mong vrious tissues. No nds of IGF-I mrna were deteted in emryoni liver t 7 dys of inution, nd therefter the mount of hepti IGF-I mrna ws inresed from 14 to 2 dys of inution. In eyes, pek in IGF-I mrna levels ourred t mid-emryogenesis, ut y ontrst, IGF-I mrna ws rely detetle in the hert throughout ll inution periods. In the musle, no signifint differene in IGF-I gene expression ws oserved during different stges of emryogenesis. After hthing, hepti IGF-I gene expression s well s plsm IGF-I onentrtion inreses rpidly with ge, rehes pek efore sexul mturity, nd then delines. The IGF-I gene expression is very sensitive to hnges in nutritionl onditions. Food-restrition nd fsting deresed hepti IGF-I gene expression nd refeeding restored IGF-I gene expression to the level of fed hikens. Dietry protein is lso very strong ftor in hnging hepti IGF-I gene expression. Refeeding with dietry protein lone suessfully restored hepti IGF-I gene expression of fsted hikens to the level of fed ontrols. In most irumstnes, IGF-I mkes omplex with speifi high-ffinity IGF-inding proteins (IGFBPs). So fr, four different IGFBPs hve een identified in vin speies nd the mjor IGFBP in hiken plsm hs een reported to e IGFBP-2. We studied the reltionship etween nutritionl sttus nd IGFBP-2 gene expression in vrious tissues of young hikens. In the liver of fed hikens, lmost no IGFBP-2 mrna ws deteted. However, fsting mrkedly inresed hepti IGFBP-2 gene expression, nd the level ws redued fter refeeding. In the gizzrd of well-fed young hikens, IGFBP-2 gene expression ws deteted nd fsting signifintly elevted gizzrd IGFBP-2 mrna levels to out doule tht of fed ontrols. After refeeding, gizzrd IGFBP-2 gene expression deresed similr to hepti IGFBP-2 gene expression. In the rin, IGFBP-2 mrna ws oserved in fed hikens nd hd signifintly deresed y fsting. In the kidney, IGFBP-2 gene expression ws oserved ut not influened y fsting nd refeeding. Reently, we hve demonstrted in vivo tht gizzrd nd hepti IGFBP-2 gene expression in fsted hikens ws rpidly redued y intrvenous dministrtion of insulin, s indited tht in young hikens the redution in gizzrd nd hepti IGFBP-2 gene expression in vivo stimulted y mlnutrition my e, in prt, regulted y mens of the inrese in plsm insulin onentrtion vi n insulin-response element. The influene of dietry protein soure (isolted soyen protein vs. sein) nd the supplementtion of essentil mino ids on gizzrd IGFBP-2 gene expression ws exmined. In oth soyen protein nd sein diet groups, the defiieny of essentil mino ids stimulted hikens to inrese gizzrd IGFBP-2 gene expression. Although mino id supplementtion of soyen protein diet signifintly deresed gizzrd IGFBP-2 mrna levels, similr redution ws not oserved in hikens fed sein diet supplemented with mino ids. This overview of nutritionl regultion of IGF-I nd IGFBP-2 gene expression in young hikens would serve for the estlishment of the supply of nutrients to diets to improve poultry prodution. (Asin-Aust. J. Anim. Si. 25. Vol 18, No. 5 : ) Key words: IGF-I, IGFBP-2, Gene Expression, Nutrition, Tissue Speifiity, Chikens INTRODUCTION It hs een well reognized tht growth hormone (GH) * This pper ws presented t the 3 rd Interntionl Symposium on Reent Advnes in Animl Nutrition during the 11 th Animl Sienes Congress, Asin-Austrlsin Assoition of Animl Prodution Soieties held in Kul Lumpur, Mlysi (Septemer 5-9 th, 24). ** Corresponding Author: K. Kit. Lortory of Animl Feeds nd Prodution, Grdute Shool of Biogriulturl Sienes, University Frm, Ngoy University, Togo, Aihi , Jpn. Tel & Fx: , E-mil: kitk@gr.ngoyu..jp 1 Ngoy Bunri University, Inzw , Jpn. Tel: , Fx: , E-mil: jokumur@ngoyunri..jp is one of nterior pituitry hormones nd tht GH relese from pituitry glnd is positively regulted y GH-relesing hormone (GHRH) nd negtively y somtosttin from the hypothlmus. Reently novel peptidyl hormone ghrelin tht hs the poteny to stimulte GH relese from the nterior pituitry ws disovered (Figure 1). In rts nd humns, ghrelin is 28-mino id ylted peptide nd minly produed in the stomh (Kojim et l., 1999). In vin speies, hiken ghrelin ws lso purified nd its DNA ws loned. Chiken ghrelin ws omposed of 26 mino ids nd possessed 54% sequene identity with humn ghrelin. The poteny of hiken ghrelin to inrese plsm GH levels ws similr to tht of rt or humn ghrelin (Kiy et l., 22). The min tivity of GH in oth vin nd mmmlin speies is to stimulte growth

2 748 KITA ET AL. Somtosttin Hypothlmus Anterior pituitry Liver Trget tissues Growth Growth hormonerelesing hormone Growth hormone Insulin-like growth ftor-i Figure 1. Shem of GHRH-GH-IGF-I xis. Ghrelin Stomh rte of nimls fter their irth. The tivity of GH is used y its inding to speifi site of GH reeptor followed y the ltertion of onformtion, so tht the intrellulr domins of GH reeptor ssoite with tyrosine kinse of the Jnus fmily (JAK2). The signl trnsdution ommened from the inding of GH to its reeptor n tivte speifi gene oding IGF-I in nuler (Xu et l., 1995). The IGF-I relesed into the irultion inds to its speifi reeptor lled y IGF type- 1 reeptor nd finlly stimultes ell prolifertion. IGF-I found in hikens hs een hrterized nd shown to e 7 mino id polypeptide (Dwe et l., 1988, Bllrd et l., 199). Some findings pointing to n importnt role of IGF-I in the ontrol of growth nd metolism in hikens, s in the se of mmmls hve een reported. For exmple, plsm IGF-I onentrtion ws highly orrelted with ody weight gin used y hnges in nutritionl onditions in young hikens (Kit et l., 1996). The DNA sequene of hiken IGF-I ws loned nd hrterized y Kjimoto nd Rotwein (1989) nd y Fwett nd Bulfield (199). The struture of hiken IGF-I gene hs lso een investigted y Kjimoto nd Rotwein (1991). In most irumstnes, IGF-I mkes omplex with speifi high-ffinity IGF-inding proteins (IGFBPs). So fr, six different IGFBPs hve een found in mmmls nd their genes hve lso een loned nd identified (Shimski nd Ling, 1991). IGFBPs re thought to prolong the hlf-life of irulting IGFs (Ketelslegers et l., 1996) nd lso t s modultors of IGF tivity (Elgin et l., 1987; Rutnen et l., 1988). In the hiken, the mjor IGFBP in the plsm hs een reported to e 3 kd protein orresponding to the ovine IGFBP-2 stndrd. Thus the predominnt IGFBP in hiken plsm differs from tht in humn plsm (Armstrong et l., 1989; Frnis et l., 199; Shoen et l., 1992; Upton et l., 1992; Morishit et l., 1993). Using the leled hiken IGF-I s proe, 3 kd nd in plsm smples from well-fed hikens ws not deteted. However, in plsm from hikens given restrited food intke or low protein diet n intense nd ws oserved t 3 kd. The sene of the 3 kd IGFBP in plsm of well-fed hikens indited tht hiken IGFBP-2 protein ws produed when nutritionl sttus ws indequte (Morishit et l., 1993; Kit et l., 1996). Chiken IGFBP-2 DNA nd gene were loned nd the tissue distriution of IGFBP- 2 mrna in hiken emryos ws exmined (Shoen et l., 1995). However, ville informtion out the reltionship etween nutrition nd IGFBP-2 gene expression in young hikens hs not een reported so fr. Strus nd Tkemoto (199) found in rts tht deresing dietry protein levels inresed IGFBP-2 gene expression in the liver, nd if this our in young hikens, it my e n importnt mehnism for the regultion of IGFBP-2 levels in vin speies. As stted ove, it seemed tht in vin speies s well s mmmlin speies hnges in plsm levels of oth IGF-I nd IGFBP-2 would e regulted y ltertion of trnsriptionl hnges in oth genes under vrious nutritionl onditions. Therefore, in the present review, we summrized the nutritionl regultion of gene expression of oth IGF-I nd IGFBP-2 in vrious tissues of young hikens. TISSUE SPECIFICITY OF IGF-I GENE EXPRESSION The in vivo studies of IGFs (IGF-I nd IGF-II), whih re struturlly homologous to proinsulin, hve demonstrted tht IGFs ind to two speifi ell surfe reeptors lled IGF type 1 nd 2 reeptors (reviewed y Roth, 1988). IGF-I n ind IGF type 1 reeptor with 15- to 2-fold higher thn IGF-II (Germin-Lee et l., 1992). Studies using knok-out mie rrying null muttion of genes oding IGF-I nd IGF type 1 reeptor reveled the importne of oth genes for emryoni development nd postntl growth (Bker, et l., 1993, Liu et l., 1993). During postntl growth in rts, the expression of IGF-I gene ws widely distriuted in vrious tissues suh s rin, lung, hert, stomh, diphrgm, kidney nd testes nd seemed to e the highest in the liver (Bornfeldt et l., 1989; Lowe et l., 1989). In vin speies s well s mmmlin speies, IGF-I mrna ws lso deteted in extrhepti tissues suh s spleen, lung, rin, kidney, hert, intestine, thymus nd musle of growing hikens, nd the most undnt expression of IGF-I mrna ws oserved in the liver (Tnk et l., 1996). Moreover, the diret evidene for the prodution of IGF-I in response to growth hormone hs een found y using hiken heptoyte ulture

3 GENE EXPRESSION OF IGF-I AND IGFBP IGF-I mrna Brin Inution periods (dys) Eye Liver Figure 2. The IGF-I gene expression in the rin, eye nd liver of hiken emryos. The numer of tissues in eh tretment ws fifteen. Mens not shring with ommon letter re signifintly different t P<.5 (,, ). system (O'Neill et l., 199; Houston nd O'Neill, 1991), nd it hs een generlly epted tht the liver is the mjor site of IGF-I prodution during post-hth growing stges of hikens. During emryogenesis of hikens, gene expression of IGF-I is distriuted widely in vrious tissues s well s growing hikens. Serrno et l. (199) reported tht IGF-I mrna trnsripts in the pnres nd rin ould e detetle y using RT-PCR while the levels in the liver were rely detetle in mid- nd lte emryogenesis (on dys 12-18). Kikuhi et l. (1991) reported tht on dys 17 nd 2 of inution IGF-I mrna ws lso deteted in eyes, skeletl musle nd rin, ut not found in the liver or hert until fter hthing. Both reserhers did not investigte gene expression of IGF-I throughout erly-to lte-emryogenesis, nd therefore we studied the tissue distriution of IGF-I mrna in vrious tissues t different stges of emryogenesis (Kit et l., 2). In this report, IGF-I mrna in eyes, hert, liver nd rest musle removed from hiken emryos t 7, 14 nd 2 dys of inution ws mesured y using rionulese protetion ssy. As shown in Figure 2, it ws reveled tht extrhepti tissues produed IGF-I mrna throughout emryogenesis nd tht the developmentl pttern of IGF-I mrna expression differed mong the tissues exmined. No nds of IGF-I mrna were deteted in the emryoni liver t 7 dys of inution, nd therefter the mount of hepti IGF-I mrna ws quntified nd inresed from 14 to 2 dys of inution. This result ws well supported y the previous findings reported y Serrno et l. (199) using RT-PCR. In ontrst to the liver, proteted IGF-I mrna frgment ws esily deteted in eyes. In eyes, pek in IGF-I mrna levels ourred t mid-emryogenesis, ut y ontrst, IGF-I mrna ws rely detetle in the hert throughout ll inution periods. These results re onsistent with previous reports y Kikuhi et l. (1991). In the musle, no signifint differene in IGF-I gene Inution periods (dys) Inution periods (dys) expression ws oserved during different stges of emryogenesis. These results onlude tht IGF-I gene expression in hiken emryos depends on the different stges of emryogenesis nd extrhepti tissues would ply n importnt role for emryo growth. NUTRITIONAL SPECIFICITY OF IGF-I GENE EXPRESSION The impt of nutrients on gene expression hs eome n re of onsiderle interest s the numer of genes oding key regultory proteins in metoli pthwys were studied in detil. Espeilly, in mmmlin speies the regultion of trnsription of the gene oding for phosphoenolpyruvte roxykinse (PEPCK), key enzyme in hepti nd renl gluoneogenesis, hs een well investigted (Gurney et l., 1994). On the other hnd, in vin speies the nlysis of physiologil nd moleulr mehnisms y whih diets nd hormones regulte the tivity of hepti mli enzyme hs een studied y reserh group of Goodridge et l. (1991, 1996). After hthing of hikens, plsm onentrtion nd hepti gene expression of IGF-I inrese rpidly with ging, reh pek efore sexul mturity, nd then deline (Huyrehts et l., 1985; Johnson et l., 199; MGuinness nd Cogurn, 199; Kikuhi et l., 1991, Kit et l., 1997). Plsm IGF-I level re lso responsive to nutrition, i. e. vrying dietry proteins, vrying dietry energy intkes, food restrition (Roserough et l., 1992, ; Roserough nd MMurtry, 1993; Kit et l., 1996; Roserough et l., 1996). Compred to plsm IGF-I onentrtion, in the hiken, studies on the response of hepti IGF-I gene expression to different nutritionl onditions hs een limited. Food-restrition (Kit et l., 1996) nd fsting (Kit et l., 1998, 22) deresed hepti IGF-I gene expression nd refeeding reovered it to the level of fed hikens, s ws in good greement with the hnges in plsm IGF-I levels (Morishit et l., 1993; Kit et l., 1997; Leili et l., 1997). Although the reovery of plsm IGF-I onentrtion y refeeding needed lmost 48 h, hepti IGF-I gene expression ws inresed within 24 h fter refeeding in fsted young hikens (Kit et l., 22). The ltertions in dietry protein nd mino id levels re lso very strong ftors to hnge plsm IGF-I onentrtion nd hepti IGF-I gene expression. Plsm onentrtion of IGF-I inresed with elevting dietry protein levels from defiieny to the requirement level (Kit et l., 1996, Kit nd Okumur, 1999), nd ove the level, it deresed signifintly (Kit nd Okumur, 1999). Refeeding with dietry protein lone suessfully restored hepti IGF-I gene expression of fsted hikens to the level of fed ontrol s well s tht of hikens refed the omplete diet (Kit et l., 1998). In rt primry heptoyto ulture system, IGF-I gene trnsription ws deresed in

4 75 KITA ET AL Brin IGFBP-2 mrna Gizzrd IGFBP-2 mrna 1 5 Fed Fsted 1h 2h 6h 24h Fed Fsted 1h 2h 6h 24h 15 Refed 15 Refed Liver IGFBP-2 mrna 1 5 Kidney IGFBP-2 mrna 1 5 Fed Fsted 1h 2h 6h 24h Fed Fsted 1h 2h 6h 24h Refed Refed Figure 3. Time ourse hnges in IGFBP-2 gene expression in the rin, gizzrd, liver nd kidney of fsted hikens fter refeeding. Chikens were fsted for 2 d nd then refed ommeril diet for 1, 2, 6 nd 24 h. The numer of irds in eh tretment ws five. Mens not shring ommon letter re signifintly different t p<.5 (,, ). response to redued provision of mino ids in ulture medium (Po et l., 1993). Although there ws virtully no findings on the influene of vrying mino id levels on hepti IGF-I gene expression in vin speies, the influene of dietry mino ids on plsm IGF-I onentrtion hs een investigted in the hiken. When young hikens were refed with protein-free diets ontining either Gly lone or ll essentil mino ids fter feeding with the protein-free diet lone, plsm IGF-I onentrtion ws reovered to level similr to tht of fed hikens (Kit et l., 22). Defiient essentil mino ids in diets suffiient with dietry protein requirement signifintly redued plsm IGF-I levels nd mino id supplement reovered it (Kit et l., 22). As it ws known tht hnges in hepti IGF-I gene expression ws positively orrelted to those in plsm IGF-I onentrtion (Kit et l., 1996), hepti IGF-I gene expression might, t lest prtilly, regulte plsm IGF-I onentrtion in young hikens given vrying mino ids levels. These issues should e eluidted in the ner future. NUTRITIONAL AND TISSUE SPECIFICITY OF IGFBP-2 GENE EXPRESSION In vin speies s well s mmmlin speies, it ws reveled tht IGF-I in the irultion mkes omplex with IGFBPs, nd DNA sequenes of severl vin IGFBPs hve een identified. In 1995, DNA of IGFBP-2 ws loned y Shoen et l. (1995), nd then IGFBP-5 DNA ws isolted y Allnder et l. (1997). In 23, two more IGFBP DNAs (IGFBP-1 nd IGFBP-4) were registerd in GenBnk (IGFBP-1: GenBnk ession no. CD & CD214364, IGFBP-4: GenBnk ession no.ay2326). However, DNAs oding IGFBP-3 nd IGFBP-6 were not identified so fr. In mmmlin speies, physiologil nd moleulr nlyses of six mjor IGFBPs hve een well investigted. For exmple, the distriution of IGFBP-2 gene expression ws preisely determined nd it ws reported tht IGFBP-2 mrna ws undnt in rin, testes nd ovry, modertely undnt in kidney, less undnt in liver nd not detetle

5 GENE EXPRESSION OF IGF-I AND IGFBP Amino id supplementtion Protein soure Soyen Csein Dietry protein level (%) 5 2 Brin IGFBP-2 mrna Gizzrd IGFBP-2 mrna Figure 4. The IGFBP-2 mrna in the rin nd gizzrd of young hikens fed 2% soyen protein diet with (+) or without mino ids (-), 2% sein diet with (+) or without mino ids (-), or 5% soyen protein diet with mino ids. The numer of irds in eh tretment ws five. Mens not shring ommon letter re signifintly different t p<.5 (,, ). in musle nd hert in dult rts (Mrgot et l., 1989). Although hiken IGFBP-2 DNA ws lso loned nd IGFBP-2 mrna ws deteted in vrious tissues of hiken emryos (Shoen et l., 1995), the distriution of IGFBP-2 gene expression hs not een investigted in post-hthing hikens. Reently, therefore, we mesured IGFBP-2 mrna in vrious tissues of growing young hikens (Kit et l., 22). As shown in Figure 3, hiken IGFBP-2 mrna ws deteted in the rin, gizzrd, liver nd kidney, ut ws rely detetle in the smll intestine. In this study, it ws lso lrified tht the undnt of IGFBP-2 mrna in the rin, gizzrd nd liver ws dependent on hnges in nutritionl onditions, nd tht in the kidney ws independent. We studied the reltionship etween nutritionl sttus nd IGFBP-2 gene expression in vrious tissues of hikens (Kit et l., 22). As shown in Figure 3, in the liver of fed hikens, lmost no IGFBP-2 mrna ws deteted. However, fsting mrkedly inresed hepti IGFBP-2 gene expression, nd this level ws retined even fter 2 h of refeeding. After 6 h of refeeding, little IGFBP-2 mrna ould e deteted in the liver. The response of hepti IGFBP-2 gene expression to fsting nd refeeding suggested two ontrry funtions of IGFBP-2 in plsm. Reently Hoeflih et l. (1999) mde trnsgeni mie rrying mouse IGFBP-2 gene nd reveled tht overexpression of IGFBP-2 regulted postntl growth negtively, potentilly y reduing the iovilvility of IGF-I. Therefore, the first funtion of IGFBP-2 in plsm is the inhiitory tivity, preventing IGF-I from ssoiting with ell surfe reeptors nd inhiiting IGF-I tivity. Seondly, IGFBP-2 my t s stle reservoir of irulting free IGF-I, whih is redily degrded y protese espeilly under mlnutritionl onditions. Furthermore, MMurtry et l. (1996) showed tht IGF-I ssoited with IGFBPs hd longer hlf-life ompred to free IGF-I. Therefore, the rpid inrese in tissue IGFBP-2 gene expression y fsting would serve for providing lrge mount of irulting IGFBP-2 to prevent the proteolysis of IGF-I y mking IGF-IGFBP omplex in plsm. In the gizzrd of well-fed young hikens, IGFBP-2 gene expression ws deteted nd fsting signifintly elevted gizzrd IGFBP-2 mrna levels to out doule tht of fed ontrols (Figure 3). After 1 h of refeeding, gizzrd IGFBP-2 gene expression remined t level similr to fsted hikens, ut therefter the level of IGFBP-2 mrna deresed to tht of fed ontrols. Although gizzrd is reognized s one of gstrointestinl orgns speifi in vin speies, the reltion of gizzrd IGFBP-2 gene expression to hnges in nutritionl onditions hs not een lrified so fr. Therefore, we investigted the influene of fsting nd refeeding on gizzrd IGFBP-2 gene expression nd reveled tht the response in gizzrd IGFBP-2 gene expression showed similr trend to tht oserved in the liver. This suggests tht the regultory mehnisms of plsm IGFBP-2 onentrtion my e ttriuted to the hnges in IGFBP-2 gene expression in the liver nd gizzrd. In the rin, IGFBP-2 mrna ws oserved in fed hiks nd hd signifintly deresed y 2 dys of fsting (Figure 3). Deresed IGFBP-2 gene expression in the rin ws not reovered to the level of well-fed hikens fter refeeding for 24 h. On the other hnd, in the kidney, IGFBP-2 gene expression ws oserved ut not influened y fsting nd refeeding. Severl yers go, Shoen et l. (1995) hve hrterized genomi DNA for hiken IGFBP-2 nd reveled tht it ontined insulin response element in the 5' upstrem region. Similr insulin response elements hve een identified in oth humn IGFBP-1 (Suwnikul et l., 1993) nd rt IGFBP-3 genes (Villfuerte et l., 1997), whose expression is negtively regulted y insulin. Reently, we hve demonstrted in vivo tht gizzrd nd hepti IGFBP-2 gene expression inresed y 2 dy-fsting ws rpidly redued y intrvenous dministrtion of ovine insulin in young hikens (Ngo et l., 21). These results indited tht in young hikens the redution in gizzrd nd hepti IGFBP-2 gene expression in vivo stimulted y mlnutrition might e, in prt, regulted y mens of the inrese in plsm insulin onentrtion vi n insulin-response element. Moreover, s it ws reported tht insulin repression of IGFBP-1 gene expression ws dependent on the mmmlin trget of rpmyin (mtor), ut independent of riosoml S6 kinse tivity (Ptel et l., 22), similr mehnism would exist in the regultory

6 752 KITA ET AL. proess of IGFBP-2 gene expression. The influene of dietry protein soure (isolted soyen protein vs. sein; rude protein (CP) 2%) nd the supplementtion of essentil mino ids on IGFBP-2 gene expression in the rin nd gizzrd of young hikens ws exmined (Kit et l., 22). In this study, the influene of feeding low protein diet (CP 5%) on tissue IGFBP-2 gene expression ws lso investigted. As shown in Figure 4, feeding the low protein diet signifintly deresed the level of rin IGFBP-2 mrna nd inresed gizzrd IGFBP-2 level, whih indited tht the influene of dietry protein defiieny on tissue IGFBP-2 gene expression seemed to e similr to the se of fsting. The signifint intertion etween protein soure nd mino id supplementtion ws oserved in gizzrd IGFBP-2 mrna level. In oth soyen protein nd sein diet groups, the defiieny of essentil mino ids stimulted to inrese gizzrd IGFBP- 2 gene expression to the level of low protein diet group. Although the mino id supplementtion into soyen protein diet signifintly deresed gizzrd IGFBP-2 mrna level, similr redution ws not oserved in hikens fed sein diet supplemented with mino ids. It ws reported tht serum mino id onentrtions were onsiderly different in rts given either dietry sein or isolted soyen protein (Horigome nd Cho, 1992). Moreover, few evidenes pointed out diretly tht severl mino ids hd the poteny to regulte the expression of hepti IGFBP-1 gene (Po et l., 1993; Jousse et l., 1998; Tkenk et l., 2, 2). These findings suggested tht different response in gizzrd IGFBP-2 gene expression to different dietry protein soure, sein nd isolted soyen protein, might e resulted y the hnge in serum mino id onentrtions, nd this issue should e eluidted in the future. CONCLUSION The impt of nutrients on gene expression hs eome n re of onsiderle interest s the numer of genes oding of growth promoting nd regulting proteins re studied in detil. In mmmlin speies, reently, the role for promoter region to regulte IGFBP-1 gene ording to nutritionl mnipultion hs een investigted preisely nd detiled knowledge hs een umulting. Compred to mmmlin speies, the informtion of regultory mehnism of IGFBPs in vin speies hs een onsiderly limited. As our reserh indited tht vrying dietry nutrients hve the poteny to improve poultry prodution through nutritionl mnipultion of severl genes oding IGF-I nd IGFBPs. We expet tht the dvned works to revel nutritionl regultion of vin growth ftors nd their inding proteins will e onduted in the ner future. REFERENCES Allnder, S. V., M. Colemn, H. Luthmn nd D. R. Powell Chiken insulin-like growth ftor inding protein (IGFBP)-5: onservtion of IGFBP-5 struture nd expression during evolution. Comp. Biohem. Physiol. 116B: Armstrong, D. G., C. O. MKy, D. J. Morrell nd C. Goddrd Insulin-like growth ftor-i inding proteins in serum from the domesti fowl. J. Endorinol. 12: Bker, J., J. P. Liu, E. J. Roertson nd A. 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Conlon, T. Sski, N. Sito nd J. Okumur Refeeding inreses hepti insulin-like growth ftor-i (IGF-I) gene expression nd plsm IGF-I onentrtion in fsted hiks. Br. Poult. Si. 39: Kit, K., J. Iwt, T. Shit, M. A. Conlon nd J. Okumur Influene of fsting on plsm insulin-like growth ftor-i onentrtion in hikens t erly stges of growth. Jpn. Poult. Si. 34: Kit, K., M. Miyzki nd J. Okumur Influene of fooddeprived hiken serum on protein synthesis of hiken emryo firolsts. Jpn. Poult. Si. 33: Kit, K., K. Ngo, N. Tned, Y. Ingki, K. Hirno, T. Shit, M. Amn Ymn, M. A. Conlon nd J. Okumur. 22. Insulin-like growth ftor inding protein-2 gene expression n e regulted y diet mnipultion in severl tissues of young hikens. J. Nutr. 132: Kit, K., C. Nod, K. Miki, K. Kino nd J. Okumur. 2. Reltionship of IGF-I mrna levels to tissue development in hiken emryos of different strins. Asin-Aust. J. Anim. Si. 13: Kit, K. nd J. Okumur Dietry protein levels lter plsm insulin-like growth ftor-i onentrtion of hiks. Jpn. Poult. 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8 754 KITA ET AL. Endorinol. 7: Po, C. I., P. K. Frmer, S. Begovi, B. C. Villfuerte, G. J. Wu, D. G. Roertson nd L. S. Phillips Regultion of insulinlike growth ftor-i (IGF-I) nd IGF-inding protein 1 gene trnsription y hormones nd provision of mino ids in rt heptoytes. Mol. Endorinol. 7: Ptel, S., P. A. Lohhed, G. Ren, S. Fumglli, M. Pende, S. C. Kozm, G. Thoms nd C. Sutherlnd. 22. Insulin regultion of insulin-like growth ftor-inding protein-1 gene expression is dependent on the mmmlin trget of rpmyin, ut independent of riosoml S6 kinse tivity. J. Biol. Chem. 277: Roserough, R. W. nd J. P. MMurtry Protein nd energy reltionship in the roiler hiken. 11. Effets of protein quntity nd qulity on metolism. Br. J. Nutr. 7: Roserough, R. W., J. P. MMurtry nd R. Vsiltos-Younken In vitro lipid metolism, growth nd metoli hormone onentrtions in hyperthyroid hikens. Br. J. Nutr. 68: Roserough, R. W., J. P. MMurtry nd R. Vsiltos-Younken Metoli nd hormonl effets of feeding hikens thyroxine nd diets ontining vried lorie to protein rtios. Nutr. Res. 12: Roserough, R. W., A. D. Mithel nd J. P. MMurtry Dietry rude protein hnges rpidly lter metolism nd plsm insulin-like growth ftor I onentrtions in roiler hikens. J. Nutr. 126: Roth, R. A Struture of the reeptor for insulin-like growth ftor II: the puzzle mplified. Si. 239: Rutnen, E. M., F. Pekonen nd T. Mkinen Solule 34K inding protein inhiits the inding of insulin-like growth ftor I to its ell reeptors in humn seretory phse endometrium: evidene for utorine/prrine regultion of growth ftor tion. J. Clin. Endorinol. Met. 66: Shoen, T. J., D. C. Beee, D. R. Clemmons, G. L. Chder nd R. J. Wldillig Lol synthesis nd developmentl regultion of vin vitrel insulin-like growth ftor-inding proteins: A model for independent regultion in extrvsulr nd vsulr omprtments. Endorinol. 131: Shoen, T. J., K. Mzuruk, R. J. Wldilling, J. Potts, D. C. Beee, G. J. Chder nd I. R. Rodriguez Cloning nd hrteriztion of hik emryo DNA nd gene for IGFinding protein-2. J. Mol. Endorinol. 15: Serrno, J., A. R. Shuldiner, C. R. Roerts, Jr., D. LeRoith nd F. De Plo The insulin-like growth ftor I (IGF-I) gene is expressed in hik emryos during erly orgnogenesis. Endorinol. 127: Shimski, S. nd N. Ling Identifition nd moleulr hrteriztion of insulin-like growth ftor inding proteins (IGFBP-1, -2, -3, -4, -5 nd -6). Prog. Growth Ftor Res. 3: Strus, D. S. nd C. D. Tkemoto Effet of dietry protein deprivtion on insulin-like growth ftor (IGF)-I nd -II, IGF inding protein-2, nd serum lumin gene expression in rt. Endorinol. 127: Suwnikul, A., S. L. Morris nd D. R. Powell Identifition of n insulin-responsive element in the promoter of the humn gene for insulin-like growth ftor inding protein-1. J. Biol. Chem. 268: Tkenk, A., K. Komori, T. Morishit, S. Tkhshi, T. Hidk nd T. Noguhi. 2. Amino id regultion of gene trnsription of rt insulin-like growth ftor-inding protein-1. J. Endorinol. 164:R Tkenk, A., N. Oki, S. Tkhshi nd T. Noguhi. 2. Dietry restrition of single essentil mino ids redues plsm insulin-like growth ftor-i (IGF-I) ut does not ffet plsm IGF-inding protein-1 in rts. J. Nutr. 13: Tnk, M., Y. Hyshid, K. Skguhi, T. Ohkuo, M. Wkit, S. Hoshino nd K. Nkshim Growth hormoneindependent expression of insulin-like growth ftor I messenger rionulei id in extrhepti tissues of the hiken. Endorinol. 137:3-34. Upton, F. Z., G. L. Frnis, M. Ross, J. C. Wlle nd F. J. Bllrd Prodution nd hrteriztion of reominnt hiken insulin-like growth ftor-i from Esherihi oli. J. Mol. Endorinol. 9: Villfuerte, B. C., W. Zho, A. C. Herington, R. Sffery nd L. S. Phillips Identifition of n insulin-responsive element in the rt insulin-like growth ftor-inding protein-3 gene. J. Biol. Chem. 272: Xu, X., S. A. Bennett, R. L. Ingrm nd W. E. Sonntg Dereses in growth hormone reeptor signl trnsdution ontriute to the deline in insulin-like growth ftor I gene expression with ge. Endorinol. 136: