Tissue distribution of rare earth elements in wild, commercial and backyard rabbits.

Rare Earth Elements (REEs), La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Sc, and Y, & two actinides, Th and U were assessed in muscle and liver tissues of wild, backyard and commercially raised rabbits through ICP-MS. Higher concentrations were found in liver in comparison to muscle tissue. Liver of wild rabbits accumulates all studied elements beyond Tm. Backyard rabbits do not show any statistically significant accumulation while commercial accumulate all beyond La, Ce, Pr, Nd, Gd and Tb. Wild rabbits were with the highest amounts for most of these elements. The different living and rearing environments of wild, backyard and commercial rabbits may affect accumulation, fate and transfer of REEs in rabbits' tissues. A dataset for establishing reference values of REEs in Lemnos island wild rabbits' is shown and the literature gap on safety limits for REEs is discussed.

Interactive effects of α-tocopheryl acetate and zinc supplementation on the antioxidant and immune systems of broilers.

1. A total of 1440 one-day-old Ross 308 male broilers were allocated to 12 dietary treatments to evaluate dose-dependent effects of α-tocopheryl acetate (α-TOA) combined with zinc (Zn) supplementation on humoral and cellular immune responses, antioxidant enzymes, serum and hepatic contents of vitamins and minerals in broilers. 2. Three levels of supplemental α-TOA (0, 150 and 300 mg/kg) and 4 levels of Zn (0, 100, 200 and 400 mg/kg) were combined as a completely randomised design as a 3 × 4 factorial arrangement. 3. Concentrations of serum α-tocopherol and selenium were influenced by the interaction of α-TOA and Zn. The interaction of α-TOA and Zn affected malondialdehyde (MDA) concentration in serum and liver (p < 0.05). Incremental amounts of supplemental Zn augmented the effects of α-TOA in reducing serum and hepatic MDA concentrations. 4. The interaction of α-TOA and Zn on antibody titres (p < 0.05) was such that increasing level of Zn at each α-TOA level led to a linear enhancement in antibody titre. Moreover, dietary supplementation with α-TOA and Zn resulted in an increase in relative weight of lymphoid organs (thymus, bursa, spleen; p < 0.05) along with an increase in humoral and cellular immune responses (p < 0.05). 5. In conclusion, α-TOA with Zn showed interactive effects in improving oxidative stability and humoral immune responses, which could result from their impact on the concentrations of antioxidant vitamins and minerals in tissues.

Dietary organic selenium addition and accumulation of toxic and essential trace elements in liver and meat of growing rabbits.

The effects of dietary organic selenium (Se) addition at 0.1, 0.5 and 2.5 mg/kg vs. an unsupplemented basal diet (BD) on the accumulation of some toxic and essential trace elements were studied in the liver and muscle tissues of growing rabbits. Dietary Se addition increased liver and muscle Se concentration linearly (P < .001), and decreased linearly Cd, As, Ni and Cr (P < .001) in liver, as well as As (P < .01) and Cd (P < .001) in muscle. Muscle Cu and Zn contents were significantly lower (P < .05) in rabbits fed 2.5 mg Se/kg diet compared to the other 3 groups. Selenium was negatively correlated with Cr, Ni, Cd and As (P < .01) in liver, and with Cu (P < .05) and Cd (P < .01) in muscle. In conclusion, dietary Se supplementation decreased the accumulation of toxic (Cd and As) and potentially toxic (Cr and Ni) trace elements in rabbits. However, at excessive quantities may negatively affect essential trace elements.

Effects of different dietary sources and levels of selenium supplements on growth performance, antioxidant status and immune parameters in Ross 308 broiler chickens.

1. Although different impacts of various sources of selenium (Se) on chicken performance have been largely studied, there is a lack of comparative experiments studying the effects of these sources on the immune system and antioxidant indices of broiler tissues. The aim of this study was to examine the effects of various sources and levels of dietary Se supplements on performance, antioxidant status and immune parameters in Ross 308 broiler chickens. 2. A total of 1200 1-d-old male broilers (Ross × Ross 308) were divided into 8 treatments with 6 replicate pens and 25 birds per pen. This experiment was conducted as a completely randomised design with a 4 × 2 factorial arrangement. Main factors included Se sources as sodium selenite (SS), Se-enriched yeast (SY), DL-selenomethionine (SM) and nano-selenium (NS) and levels at 0.1 or 0.4 mg/kg Se. 3. Dietary supplementation of organic Se sources significantly improved average daily gain (ADG), gain: feed ratio and European production efficiency factor (P < 0.05) compared to birds fed on diets supplemented with inorganic source. In addition, ADG was increased in response to increased level of supplemental Se. Based on contrast comparison, there were significant differences in these parameters between organic versus inorganic sources of Se. However, there was no difference between contrast comparisons of NS versus SM and SY. 4. Total anti-sheep red blood cell (SRBC) and Immunoglobulin G (IgG) titres and hypersensitivity were enhanced by increasing supplemental concentration of Se and using organic sources of Se rather than SS (P < 0.05). 5. Oxidation resistance assessment of tissues demonstrated that supplementation of organic sources of Se and increase in supplemental concentration of Se ameliorated glutathione peroxidase activity, total antioxidant capacity and malondialdehyde formation (P < 0.05). Mostly, there were significant differences between organic versus inorganic sources of Se in oxidation resistance. 6. Overall, dietary supplementation of 0.4 mg/kg Se from an organic source resulted in better production performance and immune system response. Moreover, minimum formation of malondialdehyde in broiler tissue was observed in birds fed on diets supplemented with SM at 0.4 mg/kg. 7. It can be concluded that SM is more effective than other sources of Se in reducing lipid oxidation.

Game meat authentication through rare earth elements fingerprinting.

Accurate labelling of meat (e.g. wild versus farmed, geographical and genetic origin, organic versus conventional, processing treatment) is important to inform the consumers about the products they buy. Meat and meat products declared as game have higher commercial value making them target to fraudulent labelling practices and replacement with non-game meat. We have developed and validated a new method for authentication of wild rabbit meat using elemental metabolomics approach. Elemental analysis was performed using rapid ultra-trace multi-element measurement by inductively coupled plasma mass spectrometry (ICP-MS). Elemental signatures showed excellent ability to discriminate the wild rabbit from non-wild rabbit meat. Our results demonstrate the usefulness of metabolic markers -rare earth signatures, as well as other trace element signatures for game meat authentication.

Seasonal variations in the fatty acid composition of Greek wild rabbit meat.

The fatty acid (FA) profile of the Longissimus thoracis et lumborum muscle (LL) was used to investigate seasonal variation (September, November and March) in wild rabbits from Lemnos Island (Greece). The n-3 FA were particularly high during early March in comparison (P<0.05) with late September and late November. Thrombogenicity index (TI) values were lower in March (P<0.05) compared to the other periods. High concentrations of odd- and branched-chain FA were found in the meat of wild rabbits; however, they were not different among the considered periods of the year. The present results showed that wild rabbit meat has a desirable FA profile, particularly during early spring, and it could be a good source of bioactive FA in human nutrition.

Effects of increasing dietary organic selenium levels on meat fatty acid composition and oxidative stability in growing rabbits.

The effects of dietary organic selenium (Se) addition at 0.1, 0.5 and 2.5mg/kg vs. an unsupplemented basal diet (BD) on performance, fatty acid (FA) composition and oxidative stability were studied in muscle tissue of growing rabbits. Muscle Se content increased (P<0.001) in a dose dependent manner with dietary Se inclusion. Saturated FA (SFA) were affected linearly (P<0.05) and quadratically (P<0.05) by dietary Se addition. Polyunsaturated FA (PUFA) increased linearly (P<0.01) resulting in a linear increase in the PUFA:SFA ratio (P<0.01) with dietary Se increment. Feeding 0.5mgSe/kg diet reduced malondialdehyde (MDA) and oxygen radical absorbance capacity (ORAC) values in the muscle, whilst 2.5mgSe/kg diet increased MDA concentrations and tended to increase ORAC values, likely indicating oxidative stress. In conclusion, dietary Se supplementation at 0.5mg/kg improves meat FA composition and oxidative stability, whereas at 2.5mg/kg may induce pro-oxidant effects.

Meta-analysis of selenium accumulation and expression of antioxidant enzymes in chicken tissues.

A meta-analysis integrating results of 40 selenium (Se) supplementation experiments that originated from 35 different controlled randomized trials was carried out in an attempt to identify significant factors that affect tissue Se accumulation in chicken. Examined factors included: Se source (12 different sources examined), type of chicken (laying hens or broilers), age of birds at the beginning of supplementation, duration of supplementation, year during which the study was conducted, sex of birds, number of chickens per treatment, method of analysis, tissue type, concentration of Se determined and Se added to feed. A correlation analysis was also carried out between tissue Se concentration and glutathione peroxidase activity. Data analysis showed that the factors significantly affecting tissue Se concentration include type of chicken (P=0.006), type of tissue (P<0.001) and the analytical method used (P=0.014). Although Se source was not found to affect tissue Se concentration (overall P>0.05), certain inorganic (sodium selenite), calcium selenite, sodium selenate and organic sources (B-Traxim Se), Se-yeast, Se-malt, Se-enriched cabbage and Se-enriched garlic as well as background Se level from feed ingredients were found to significantly affect tissue Se concentration. The Se accumulation rate (estimated as linear regression coefficient of Se concentrations to Se added to feed) discriminated between the various tissues with highest values estimated in the leg muscle and lowest in blood plasma. Correlation analysis has also shown that tissue Se concentration (pooled data) was correlated to Se added to feed (r=0.529, P<0.01, log values) and to glutathione peroxidase activity (r=0.332, P=0.0478), with the latter not being correlated with Se added to feed. Although significant factors affecting Se concentration were reported in the present study, they do not necessarily indicate the in vivo function of the antioxidant system or the level of accumulated Se as other factors, not examined in the present study, may interact at the level of trace element absorption, distribution and retention.

The role of organic selenium in cadmium toxicity: effects on broiler performance and health status.

This work was part of a project designed to assess whether organic selenium (Se) can protect against the toxic effects of cadmium (Cd). A total of 300 1-day-old, as hatched, broilers were randomly distributed in four dietary treatments with five replicate pens per treatment. In T1 treatment, broilers were fed a diet with 0.3 mg/kg added Se, as Se-yeast, without added Cd; in T2, broilers were fed a diet with 0.3 mg/kg Se and 10 mg/kg Cd; in T3, broilers were fed a diet with 0.3 mg/kg Se and 100 mg/kg of Cd; and in T4 treatment broilers were fed a diet with 3 mg/kg Se and 100 mg/kg Cd. The Cd was added to diets T2, T3 and T4 as CdCl2. On the 4th and 6th week, two broilers per replicate pen were killed in order to obtain whole blood, liver, kidney and breast samples. Body mass, feed conversion ratio and mortality were assessed and haematological analyses were performed. Se and Cd levels in tissues were analysed by inductively coupled plasma mass spectrometry. Broilers supplemented with 0.3 mg/kg Se can tolerate low levels of Cd added to the diets, as there were no significant negative effects on the examined performance parameters, whereas addition of excess Cd led to an impairment of broilers' performance. Mortality of broilers did not differ between the four dietary treatments at any interval point or the whole period. The examined haematological parameters such as haematocrit, total blood protein concentration, and leukocytes types ranged within physiological values, revealing no negative health effects after simultaneous Cd and Se addition. The present study indicated that Se can help against the negative effects of Cd, but cannot counteract all of its negative effects.

Supranutritional selenium level affects fatty acid composition and oxidative stability of chicken breast muscle tissue.

A total of 128 broilers were used to investigate the effect of selenium (Se) on fatty acid (FA) composition and oxidative stability of lipids in the breast muscle tissue. There were 4 replicates of 4 dietary treatments: T1 (basal diet with no added Se), T2 (T1 with 0.15 mg Se added per kg diet), T3 (T1 with 0.3 mg Se added per kg diet) and T4 (T1 with 3.0 mg Se added per kg diet). A yeast source was used for added Se. Breast muscle tissue was collected from two chickens per replicate pen for the determination of Se concentration by ICP-MS, FA profile by GC and lipid oxidation using thiobarbituric acid reactive substances method. Addition of supranutritional Se levels to chicken diets leads to the production of Se-enriched meat. Consumption of 100 g of breast meat from chickens fed diets supplemented with 0.15, 0.3 and 3 mg Se per kg of diet can provide 26, 41 and 220 µg of Se, respectively. Long-chain polyunsaturated fatty acids namely C20:3n-6, C20:4n-6, C20:5n-3, C22:5n-3 and C22:6n-3 increased linearly (p = 0.047, p < 0.001, p = 0.023, p = 0.003 and p = 0.002, respectively) as the Se inclusion levels in the diets increased. At slaughter, a linear decrease in lipid oxidation (p = 0.019) was observed with Se addition, possibly attributed to the antioxidant properties of Se. Addition of supranutritional Se to chicken diets, at levels well below those causing toxicity, leads to production of Se-enriched meat, protection of health-promoting long-chain FA like C20:5n-3 and C22:6n-3 and protection of meat quality from oxidation at day 1 after slaughter.

The role of selenium in cadmium toxicity: interactions with essential and toxic elements.

1. The study was part of a project designed to investigate if organic selenium (Se) can ameliorate the toxic effects of cadmium (Cd). The main objective of the present study was to investigate, in the chicken, the interactions between Se, Cd and the following elements: Sb, Ca, Cr, Co, Cu, Fe, Pb, Mg, Mn, Mo, Ni, V and Zn. 2. A total of 300 1-d-old chickens (broilers) were randomly distributed among 4 dietary treatments with 5 replicate pens per treatment. In T1, chickens were fed on a diet with 0·3 mg/kg added Se, without added Cd. In T2, chickens were fed on a diet with 0·3 mg/kg Se and 10 mg/kg Cd. In T3, chickens were fed on a diet with 0·3 mg/kg Se and 100 mg/kg of Cd added and in T4 treatment, chickens were fed on a diet with 3 mg/kg Se and 100 mg/kg Cd added. Se was added as Se-yeast. Cd was added as cadmium chloride (CdCl2). On d 28 and 42, two chickens per replicate pen were killed for collection of whole blood, liver, kidney and breast muscle samples. Samples were analysed by ICP-MS. The data were analysed using a multivariate linear model. 3. While low Cd concentrations in the diet led only to an increase of Cd concentration in the examined tissues, addition of high concentrations of Cd increased the concentration of Cd, Cu, Sb and V and decreased that of Se, Mn and Fe. Addition of high Se concentrations did not significantly reduce Cd concentration. 4. Prior to model application, correlations of 78 elements were noted, while after model application 39 correlations were noted. Most notably, Cd was correlated with Ca, Co, Cu and Mg, while Se was correlated with Mn. 5. The present study revealed several correlations between essential, probably essential and toxic elements illustrating the importance of the balance between pro-oxidants and antioxidants.

Terpenes transfer to milk and cheese after oral administration to sheep fed indoors.

Terpenes have been proposed as potential biomarkers in verifying the diets of grazing animals. A study of the relationships between the intake of terpenes and their presence in animal tissues (blood and milk) as well as in the final product (cheese) was conducted. Eight dairy sheep were divided into two equal groups, representing control (C) and treatment group (T). In T group oral administration of a mixture of terpenes, α-pinene, limonene and ß-caryophyllene, was applied over a period of 18 days. Blood and milk samples were collected regularly and terpenes were identified by extraction using petroleum ether and the solid phase micro-extraction (SPME) method, respectively, followed by GC-MS analysis. Cheese was produced, from C and T animals separately, twice during the period of terpenes oral administration. Terpenes contents and chemical properties of the produced cheeses were investigated. Limonene and α-pinene were found in all blood and milk samples of the T group after a lag-phase of 2 days, while ß-caryophyllene was detected in few plasma samples and in all milk samples. None of the terpenes was traced in blood and milk of C animals. The contents of cheese, in dosed terpenes, presented a more complicated pattern suggesting terpenes non-credible as biomarkers. We conclude terpenes can be used as biomarkers for authentification of ewes' milk, but further research is required on factors affecting their transfer to dairy products from grazing diets.

Transfer of orally administered terpenes in goat milk and cheese.

The objective of the present study was to investigate the relationships between terpenes' intake and their presence in animal tissues (blood and milk) as well as in the final product (cheese). Eight dairy goats were divided in two balanced groups, representing control (C) and treatment (T) group. In T group oral administration of a mixture of terpenes (α-pinene, limonene and ß-caryophyllene) was applied over a period of 18 d. Cheese was produced, from C and T groups separately, on three time points, twice during the period of terpenes' oral administration and once after the end of experiment. Terpenes were identified in blood by extraction using petroleum ether and in milk and cheese by the use of solid phase micro-extraction (SPME) method, followed by GC-MS analysis. Chemical properties of the milk and the produced cheeses were analyzed and found not differing between the two groups. Limonene and α-pinene were found in all blood and milk samples of the T group after a lag-phase of 3 d, while ß-caryophyllene was determined only in few milk samples. Moreover, none of the terpenes were traced in blood and milk of C animals. In cheese, terpenes' concentrations presented a more complicated pattern implying that terpenes may not be reliable feed tracers. We concluded that monoterpenes can be regarded as potential feed tracers for authentification of goat milk, but further research is required on factors affecting their transfer.

Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I.

Insulin and parathyroid hormone (PTH) regulate glucose metabolism in bone cells. In order to differentiate between the effects of these hormones and to compare the potency of insulin with that of insulin-like growth factor (IGF) I, we treated rat bone-derived osteoblastic (PyMS) cells for different time periods and at different concentrations with insulin, IGF I, or PTH, and measured [1-(14)C]-2-deoxy-D-glucose (2DG) uptake and incorporation of D-[U-(14)C] glucose into glycogen. 2DG uptake was Na-independent with an apparent affinity constant (K (M)) of ~2 mmol/l. Expression of the high affinity glucose transporters (GLUT), GLUT1 and GLUT3 but not of GLUT4, was found by Northern and Western analysis. Similar to the findings with primary rat osteoblasts, but distinct from those in rat fibroblasts, 2DG uptake and glycogen synthesis were increased in this cell line after exposure to low concentrations (0.1 nmol/l and above) of PTH. IGF I at low doses (0.3 nmol/l and above) or insulin at higher doses (1 nmol/l and above) stimulated 2DG uptake and [(3)H] thymidine incorporation into DNA. 2DG transport was enhanced already after 30 min of IGF I treatment whereas the effect of PTH became significant after 6 h. It is concluded that IGF I rather than insulin may be a physiological regulator of 2DG transport and glycogen synthesis in osteoblasts.

Selenium affects the expression of GPx4 and catalase in the liver of chicken.

A total of 128 chickens (Gallus gallus, broilers) were used to investigate the effect of organic selenium (Se) in expression of catalase (CAT) and phospholipid hydroperoxidase 4 (GPx4) genes. There were 4 replicates of 4 dietary treatments: T1 (basal diet with no added Se), T2 (T1 with 0.15 ppm Se added), T3 (T1 with 0.3 ppm Se) and T4 (T1 with 3.0 ppm Se). At 4th and 6th week, 2 chickens per replicate pen were sacrificed for whole blood and liver sample collections. Samples were analyzed for total Se by ICP-MS and gene expression by RT-PCR. Dietary supplementation with organic Se (Se-yeast) readily elevated its concentration in the tissues. GPx4 mRNA levels, pooled for both ages, of chickens fed T3 and T4 diets were significantly reduced compared to those fed diet T1 by 47% and 77% respectively, while that of T2 did not differ. Liver CAT mRNA levels at 4th week were significantly decreased as Se supplementation increased, while at 6th week, were not significantly affected by Se. The study showed that liver GPx4 mRNA levels could be down-regulated by excess of Se. It is possible that reserves built by excess of Se meet antioxidant requirements and no additional GPx4 transcription is necessary.

Selenoproteins and maternal nutrition.

Selenium (Se) is an essential trace element of fundamental importance to health due to its antioxidant, anti-inflammatory and chemopreventive properties attributed to its presence within at least 25 selenoproteins (Sel). Sel include but not limited to glutathione peroxidases (GPx1-GPx6), thioredoxin reductases (TrxR1-TrxR3), iodothyronine deiodinases (ID1-ID3), selenophosphate synthetase 2 (SPS2), 15-kDa Sel (Sel15), SelH, SelI, SelK, SelM, SelN, SelO, SelP, SelR, SelS, SelT, SelV, SelW, as well as the 15-kDa Sel (Fep15), SelJ and SelU found in fish. In this review, we describe some of the recent progress in our understanding of the mechanisms of Sel synthesis. The impact of maternal Se intake on offspring is also discussed. The key regulatory point of Sel synthesis is Se itself, which acts predominantly at post-transcriptional levels, although recent findings indicate transcriptional and redox regulation. Maternal nutrition affects the performance and health of the progeny. Both maternal and offspring Se supplementations are essential for the antioxidant protection of the offspring. Prenatal Se supplementation provides an effective antioxidant system that is already in place at the time of birth while, postnatal Se supplementation becomes the main determinant of progeny Se status after the first few days of progeny life.

Effects of insulin--like growth factor-I treatment on the endocrine pancreas of hypophysectomized rats: comparison with growth hormone replacement.

BACKGROUND: In GH-deficient humans, GH and IGF-I treatment cause opposite effects on serum insulin concentrations and insulin sensitivity. This finding contrasts with the somatomedin hypothesis that IGF-I mediates GH action, as postulated for skeletal growth, and raises the question whether GH-induced IGF-I acts on the endocrine pancreas in the same way as administered IGF-I. OBJECTIVE: To compare the effects of the two hormones on the endocrine pancreas of hypophysectomized rats. METHODS: Animals were infused for 2 days, via miniosmotic pumps, with IGF-I (300 microg/day), GH (200 mU/day) or vehicle. We measured (i) glucose, IGF-I, insulin, C-peptide and glucagon in serum and (ii) IGF-I, insulin and glucagon mRNAs and peptides in the pancreas by radioimmunoassay, immunohistochemistry and northern analysis. RESULTS: Both GH and IGF-I treatment increased serum and pancreatic IGF-I but, unlike GH, IGF-I treatment strongly reduced serum insulin and C-peptide (and, to a lesser extent, serum glucagon). Nevertheless, the animals did not become hyperglycaemic. GH, but not IGF-I, increased pancreatic insulin and glucagon content, as also indicated by immunohistochemistry, and increased IGF-I mRNA. Neither GH nor IGF-I caused significant changes in insulin and glucagon mRNA. CONCLUSIONS: The decrease in serum insulin and C-peptide by IGF-I treatment without significant changes in insulin gene expression and pancreatic insulin content suggests inhibition of insulin secretion. Within this setting, the absence of hyperglycaemia points to enhanced insulin sensitivity, although an insulin-like action of infused IGF-I may have partially compensated for the decreased insulin concentrations. GH-induced circulating or pancreatic IGF-I, or both, does not mimic the pancreatic effects of infused IGF-I in the absence of GH, suggesting that GH may counteract the action of GH-induced IGF-I on the endocrine pancreas.

Regulation of phosphate (Pi) transport and NaPi-III transporter (Pit-1) mRNA in rat osteoblasts.

In osteoblasts only the type III Na(+)-dependent phosphate (NaPi) transporter isoforms Pit-1 and Pit-2 have been identified. We tested the effects of extracellular Pi, Ca(2+) and IGF-I on Na(d)Pi transport and Pit-1 or Pit-2 mRNA expression in rat osteoblastic (PyMS) cells. The v(max) of Na(d)Pi transport was higher in cells kept in Pi-free, serum-free medium for 24 h than in controls at 1 mM Pi (2.47+/-0.20 vs 1.83+/-0.17 nmol/mg protein x 10 min). The apparent affinity constant (K(M)) for Pi remained unchanged. Pi withdrawal for 24 h did not impair cell viability whereas increasing the extracellular Pi to 5 mM resulted in cell death. Pit-1 (but not Pit-2) mRNA was upregulated following Pi deprivation, Ca(2+) treatment or after treatment with 1 nM IGF-I, known to stimulate Na(d)Pi transport and cell proliferation. IGF-I also stimulated Na(d)Pi transport and Pit-1 mRNA in primary rat calvarial osteoblasts. Expression of Pit-1 mRNA in vivo and the coordinate regulation of Pit-1 mRNA and Pi transport in osteoblastic cells suggest that Pit-1 is a candidate transporter of physiological relevance in bone.

Phex cDNA cloning from rat bone and studies on phex mRNA expression: tissue-specificity, age-dependency, and regulation by insulin-like growth factor (IGF) I in vivo.

Phosphate regulating gene with homology to endopeptidases on the X chromosome (Phex) inactivating mutations cause X-linked hypophosphatemia (XLH). The disorder is characterized by decreased renal phosphate (Pi) reabsorption in both humans and mice, in the latter shown to be due to a reduction in mRNA and protein of type II sodium-dependent phosphate cotransporter (NadPi-II). To gain insight into the physiological role of Phex, we cloned the rat cDNA and examined tissue-specific and age-dependent mRNA expression. The rat full-length cDNA (2247 nucleotides) shares 96 and 90% identity with the mouse and human cDNA, respectively. We found 6.6 kb Phex transcripts in calvarial bone and lungs, and a weaker signal in liver of newborn rats. In adult animals, Phex mRNA signals were weaker in bone and lungs and absent in liver. Phex mRNA expression in bones and NadPi-I and -II cotransporter mRNA expression in kidney were also determined in hypophysectomized rats. These rats, which lack GH and IGF I, stop growing and exhibit decreased serum Pi levels. Treatment during 6 days with IGF I stimulated growth and increased serum Pi. Phex and NadPi-II cotransporter mRNA levels were higher in IGF I than in vehicle-treated animals, while mRNA expression of NadPi-I, 1alpha-hydroxylase and 24-hydroxylase and serum levels of calcitriol remained unaffected. Age-dependency of Phex expression suggests a role for Phex in Pi retention during growth. Moreover, our findings indicate that an increase in Phex expression in bones under the influence of IGF I may contribute to increased serum Pi by enhancing renal phosphate reabsorption. Because IGF I treatment increased NadPi-II mRNA expression and serum Pi, IGF I appears to act at least partially at pretranslational levels to increase NadPi-II mediated renal Pi retention in growing rats.