Long-term effects of castration on the skeleton of male rhesus monkeys (Macaca mulatta).

While osteopenia (OPE) and osteoporosis (OPO) have been studied in various species of aging nonhuman primates and extensively in ovariectomized rhesus and cynomolgus macaques, there is virtually no information on the effects of castration on the skeleton of male nonhuman primates. Most information on castrated male primates comes from a few studies on the skeletons of eunuchs. This report used a subset of the Caribbean Primate Research Center's (CPRC) Cayo Santiago (CS) rhesus macaque skeletal collection to qualitatively and quantitatively compare the bone mineral density (BMD) of castrated and age-matched intact males and, thereby, determine the long-term effects of castration (orchidectomy) on bone. Lumbar vertebrae, femora, and crania were evaluated using dual-energy X-ray absorptiometry (DEXA or DXA) and digital radiography augmented, when fresh tissues were available, with autoradiography and histology. Results confirmed physical examinations of long bones that castration causes changes in the skeleton of male rhesus macaques similar to those found in eunuchs, including OPE and OPO of the vertebrae and femora, thinning of the skull, and vertebral fractures and kyphosis of the spine more severe than that caused by normal aging alone. Also like eunuchs, some castrated CS male rhesus monkeys had a longer life span than intact males or females. Based on these results and the effects of castration on other tissues and organs of eunuchs, on behavior, hormone profiles and possibly on cognition and visual perception of human and nonhuman primates, and other mammals, castrated male rhesus macaques should be used with caution for laboratory studies and should be considered a separate category from intact males. Despite these caveats, the castrated male rhesus macaque should make an excellent animal model in which to test hormone replacement therapies for boys and men orchidectomized for testicular and prostate cancer.

Autoradiography and inmmunolabeling suggests that lizard blastema contains arginase-positive M2-like macrophages that may support tail regeneration.

BACKGROUND: The regenerating blastema of the tail in the lizard Podarcis muralis contains numerous macrophages among the prevalent mesenchymal cells. Some macrophages are phagocytic but others are devoid of phagosomes suggesting that they have other roles aside phagocytosis. METHODS: The presence of healing macrophages (M2-like) has been tested using autoradiographic, immunohistochemical and ultrastructural studies. RESULTS: Autoradiography shows an uptake of tritiated arginine in sparse cells of the blastema and in the regenerating epidermis. Bioinformatics analysis suggests that epitopes for arginase-1 and -2, recognized by the employed antibody, are present in lizards. Immunofluorescence shows sparse arginase immunopositive macrophages in the blastema and few macrophages also in the apical wound epidermis. The ultrastructural study shows that macrophages contain dense secretory granules, most likely inactive lysosomes, and small cytoplasmic pale vesicles. Some of the small vesicles are arginase-positive while immunolabeling is very diffuse in the macrophage cytoplasm. CONCLUSIONS: The presence of cells incorporating arginine and of arginase 1-positive cells suggests that M2-like macrophages are present among mesenchymal and epidermal cells of the regenerative tail blastema. M2-like macrophages may promote tail regeneration differently from the numerous pro-inflammatory macrophages previously detected in the scarring limb. The presence of M2-like macrophages in addition to hyaluronate, support the hypothesis that the regenerative blastema of the tail in lizards is an immuno-privileged organ where cell proliferation and growth occur without degenerating in a tumorigenic outgrowth.

Resolution, sensitivity and precision with autoradiography and small animal positron emission tomography: implications for functional brain imaging in animal research.

Quantitative autoradiographic methods for in vivo measurement of regional rates of cerebral blood flow, glucose metabolism, and protein synthesis contribute significantly to our understanding of phsysiological and biochemical responses of the brain to changes in the environment. A disadvantage of these autoradiographic methods is that experimental animals can be studied only once. With the advent of small animal positron emission tomography (PET) and with increases in the sensitivity and spatial resolution of scanners it is now possible to use adaptations of these methods in experimental animals with PET. These developments allow repeated studies of the same animal, including studies of the same animal under different conditions, and longitudinal studies. In this review we summarize the tradeoffs between the use of autoradiography and small animal PET for functional brain imaging studies in animal research.

Flumequine in Atlantic salmon Salmo salar: disposition in fish held in sea water versus fresh water.

14C-labeled flumequine was administered as a single oral (5 mg kg(-1), 86 microCi kg(-1)) or intravenous (5 mg kg(-1), 82 microCi kg(-1)) dose to Atlantic salmon Salmo salar held in sea water or in fresh water. The absorption, tissue distribution and elimination were determined by means of liquid scintillation counting and whole-body autoradiography. The drug was rapidly absorbed and extensively distributed in all groups of fish. Radiolabeled compound was present in blood and muscle for more than 8 wk in the freshwater groups. In the seawater groups, however, no radioactivity was detected in the blood and muscle after 4 d and 2 wk, respectively. It was concluded that flumequine was eliminated at a substantially higher rate from Atlantic salmon in sea water than in fresh water.

Disposition of 14C-flumequine in eel Anguilla anguilla, turbot Scophthalmus maximus and halibut Hippoglossus hippoglossus after oral and intravenous administration.

The absorption, distribution and elimination of 14C-labelled flumequine were studied using whole body autoradiography and liquid scintillation counting. Flumequine was administered to eel Anguilla anguilla, turbot Scophthalmus maximus and halibut Hippoglossus hippoglossus intravenously and orally as a single dose of 5 mg kg(-1), corresponding to 0.1 mCi kg(-1). The turbot and halibut studies were performed in salt water (salinity of 32%) at temperatures of 16 +/- 1 degrees C (turbot) and 9.5 +/- 0.5 degrees C (halibut). The eel study was conducted in fresh water at 23 +/- 1 degrees C. In the intravenously administered groups flumequine was rapidly distributed to all major tissues and organs. After oral administration flumequine also appeared to have rapid and extensive absorption and distribution in all 3 species. After the distribution phase, the level of flumequine was higher in most organs and tissues than in the blood, except in muscle and brain. The most noticeable difference between the species was the slow elimination of flumequine from eel compared to turbot and halibut. In orally administered eels, substantial amounts of flumequine remained in all major organs/tissues for 7 d. At 28 d significant levels of flumequine were present in liver, kidney and skin (with traces in muscle), and at the last sampling point (56 d) in eye, bone, bile and posterior intestine. In orally administered turbot significant levels of flumequine were observed over 96 h in bile, urine, bone, skin, intestine and eye, and traces were detected over 28 d in bone and eye in addition to a significant level in bile. In orally administered halibut, significant levels of flumequine were observed in bile, skin, intestine and eye over 96 h. Traces were present in skin and eye over 7 d. The maximal flumequine concentrations in blood were calculated to be 2.5 mg equivalents l(-1) (eel at 12 h), 0.8 mg l(-1) (turbot at 6 h) and 0.6 mg l(-1) (halibut at 6 h) after oral administration.

Plasma and bile antibodies of the teleost Trematomus bernacchii specific for the nematode Pseudoterranova decipiens.

We investigated the occurrence of antibodies against protein antigens of the nematode parasite Pseudoterranova decipiens in the plasma and bile of the Antarctic teleost Trematomus bernacchii. Three different P. decipiens protein solutions were prepared: excreted/secreted proteins from live larvae (ESP); surface-associated proteins obtained by mild extraction of larval bodies (SAP); and cuticular soluble proteins recovered by extraction in strong reducing conditions (CSP). Using different immunoassays, these 3 preparations were tested for their ability to bind fish antibody. As determined by ELISA, the specific antibody binding activity was higher in SAP than in CSP. As determined by dot-blot immunoassay, the specific antigen binding activity versus SAP was higher in bile than in plasma antibodies. A different number of antigenic components of SAP and ESP were identified by immunoblotting performed with plasma or bile antibodies. These results led to the conclusion that T. bernacchii parasitism by nematodes involves plasma and bile anti-parasite antibodies. Furthermore bile antibodies were found to be more reactive and more heterogeneous than plasma.

Time course and magnitude of synthesis of heat-shock proteins in congeneric marine snails (Genus tegula) from different tidal heights.

The time course and magnitude of the heat-shock response in relation to severity of thermal stress are important, yet poorly understood, aspects of thermotolerance. We examined patterns of protein synthesis in congeneric marine snails (genus Tegula) that occur at different heights along the subtidal to intertidal gradient after a thermal exposure (30 degrees C for 2.5 h, followed by 50 h recovery at 13 degrees C) that induced the heat-shock response. We monitored the kinetics and magnitudes of protein synthesis by quantifying incorporation of 35S-labeled methionine and cysteine into newly synthesized proteins and observed synthesis of putative heat-shock proteins (hsp's) of size classes 90, 77, 70, and 38 kDa. In the low- to mid-intertidal species, Tegula funebralis, whose body temperature frequently exceeds 30 degrees C during emersion, synthesis of hsp's commenced immediately after heat stress, reached maximal levels 1-3 h into recovery, and returned to prestress levels by 6 h, except for hsp90 (14 h). In contrast, in the low-intertidal to subtidal species, Tegula brunnea, for which 2.5 h at 30 degrees C represents a near lethal heat stress, synthesis of hsp's commenced 2-14 h after heat stress; reached maximal levels after 15-30 h, which exceeded magnitudes of synthesis in T. funebralis; and returned to prestress levels in the case of hsp90 (50 h) and hsp77 (30 h) but not in the case of hsp70 and hsp38. Exposures to 30 degrees C under aerial (emersion) and aquatic (immersion) conditions resulted in differences in hsp synthesis in T. brunnea but not in T. funebralis. The different time courses and magnitudes of hsp synthesis in these congeners suggest that the vertical limits of their distributions may be set in part by thermal stress.

32P-postlabelling analysis of DNA adducts and EROD induction as biomarkers of genotoxin exposure in dab (Limanda limanda) from British coastal waters.

Dab (Limanda limanda) were sampled from a number of polluted and unpolluted areas in British coastal waters. The 32P-postlabelling assay was used to analyse the level of aromatic/hydrophobic DNA adducts in pooled samples of liver tissue. The mean levels of DNA adducts detected from areas known to receive anthropogenic pollutants ranged from 4.0 to 26.8 adducts per 10(8) nucleotides, with all sites containing samples displaying DNA adduct profiles consisting of diagonal radioactive zones. In contrast no DNA adducts were detectable in samples from an unpolluted reference site. The ranking of polluted sites based on DNA adduct levels did not correspond with the ranking of sites based on sediment associated polycyclic aromatic hydrocarbon levels, highlighting the problem of linking the presence of contamination with detectable biological responses. No correlation could be found in this study between EROD activity and the level of DNA adducts.

Altered intestinal macrophage phenotype in ovine paratuberculosis.

The expression of macrophage surface markers that are likely to be important in antigen presentation and cell interactions was examined in normal sheep and those with clinical paratuberculosis. Immunohistological studies demonstrated that intestinal macrophages in diseased sheep expressed MHC class II, LFA-1 and CR4 antigens weakly compared with normal tissues. Reverse transcriptase-polymerase chain reaction analysis of MHC class II mRNA in intestinal whole tissue samples showed no significant difference between control and diseased groups. A reduction in molecules such as MHC class II and LFA-1 on the surface of infected macrophages could have implications for survival of the intracellular mycobacteria and the persistence of infection.

Proteoglycan metabolism of equine articular chondrocytes cultured in alginate beads.

Equine chondrocytes were cultured in vitro for 30 days in ionically gelled alginate beads. The alginate polymerises into a stable gel in the presence of divalent cations (calcium), and rapid depolymerisation in the presence of a calcium chelator releases the viable chondrocytes. The chondrocytes maintained a spherical appearance for 30 days in culture, in marked contrast to monolayer cultures, which develop a dedifferentiated fibroblastic morphology. The major proteoglycan molecule produced by the encapsulated chondrocytes was aggrecan, of similar hydrodynamic size to aggrecan molecules present in the matrix of the articular cartilage from which the cells were harvested. Link protein, keratan sulphate and chondroitin sulphate were also synthesised by the chondrocytes, as demonstrated by immunohistochemistry. The proteoglycan secreted by the chondrocytes consisted of at least two pools, one remaining adjacent to the cell and forming a dense, cell-associated matrix, and another migrating more peripherally into the intercellular compartment. Newly synthesised proteoglycans extracted from the pericellular matrix and the intercellular matrix were similar in hydrodynamic size and aggregated in the presence of exogenous hyaluronan.

Distribution of substance P binding sites in equine airways.

Autoradiography with [125I]-Bolton Hunter substance P ([I]-BHSP) was used to detect substance P binding sites in the equine lung. Specific [I]-BHSP binding sites were very dense over small bronchial vessels, tracheobronchial glands and airway epithelium in large and small airways. The density of [I]-BHSP binding sites over airway smooth muscle was much lower than in the preceding tissues. Competition with an excess of either a specific neurokinin 1 receptor agonist, or a specific neurokinin 2 receptor agonist indicated that most specific [I]-BHSP binding sites in the equine lung represent neurokinin 1 receptors. The receptor-mediated effects of substance P in the equine lung are most likely to involve regulation of vascular tone and airway secretions based upon the density of specific [I]-BHSP binding sites in these tissues. Activation of intrapulmonary afferent nerves containing Substance P by noxious stimuli such as inhaled allergens or irritants may lead to increased mucus secretion and decreased airway diameter due to vascular congestion.

Tachykinin receptors in the equine pelvic flexure.

Tachykinins, of which substance P (SP) is the prototype, are neuropeptides which are widely distributed in the nervous systems. In the equine gut, SP is present in enteric nerves and is a powerful constrictor of enteric muscle; in other species, SP is also known to have potent vasodilatory and pro-inflammatory effects. The specific effects of SP are determined by the subtype of receptor present in the target tissue. There are 3 known subtypes of tachykinin receptors, distinguished by their relative affinities for SP and other tachykinins. The distribution of SP binding sites in the equine pelvic flexure was determined using 125I-Bolton Hunter SP (I-BHSP) autoradiography. Most I-BHSP binding sites were determined to be saturable and specific, therefore presumably representing tachykinin receptors. The greatest degree of I-BHSP binding occurred over very small vessels, and over the muscularis mucosae; I-BHSP binding was also intense over the circular muscle of the muscularis externa and mucosa, and present, although less intense, over the longitudinal muscle of the muscularis externa. Competition of I-BHSP with specific receptor agonists for binding sites in the equine pelvic flexure were used to determine the subtypes of tachykinin receptors present. The neurokinin-1 receptor subtype predominated in the equine pelvic flexure, followed by the neurokinin-3 receptor subtype.

Comparison of a radioactive and non-radioactive method for sequencing foot and mouth disease virus isolates.

The authors compare the radioactive method of detecting foot and mouth disease virus sequence products with a non-radioactive, silver stain sequencing method. The latter was found to compare favourably to the radioactive technique for detecting such products. The silver stain sequencing method was simple and did not require expensive specialised equipment. This new approach will be particularly useful in developing countries, since the method does not depend on the availability of fresh radioactive isotopes and is also safer and considerably cheaper.

Age and breed differences in thyroid hormones, insulin-like growth factor (IGF)-I and IGF binding proteins in female horses.

A survey with horses was conducted to determine whether plasma concentrations of triiodothyronine (T3), thyroxine (T4), insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP) change as horses grow, mature sexually, and age. Jugular blood was sampled from Standardbred fillies and mares at ages 0, 1, 7, and 14 d, at 1, 2, 4, 5, 6, and 9 mo, and at 5 to 8 and 16 to 22 yr (n = 5 to 18). In a second survey, we measured the same variables in eight breeds of horses with markedly different adult body sizes, from Miniatures to Friesians. Plasma T3, T4, and IGF-I were determined by radioimmunoassays validated for horses, and IGFBP were estimated from radioligand assay following separation of the IGFBP by SDS-PAGE electrophoresis. Plasma T3 decreased (P < .01) nearly continuously from 7.9 ng/mL on the day of birth to .9 ng/mL at 6 mo, and then changed little from .7 ng/mL at 9 mo to .5 ng/mL in mares 16 to 22 yr old. Similarly, T4 declined (P < .01) from 233 ng/mL on the day of birth to 49 ng/mL at 14 d and varied from 35 to 9 ng/mL among all of the older age groups. Plasma concentrations of IGF-I increased (P < .01) from 285 ng/mL on the day of birth to 572 ng/mL at 14 d, remained relatively constant until 9 mo of age (530 ng/mL), and then declined (P < .01) to low levels (295 ng/mL) in the oldest mares. We detected six IGFBP. The two smallest IGFBP (26 and 39 kDa) were highest during the first 14 d after birth and lowest (P < .01) in aged mares. The four larger IGFBP were lowest at birth and increased to the highest values during the most rapid growth period, but these changes were not significant (P > .20). In agreement with data for other species, our data suggest that IGF-I and IGFBP modulate growth in horses. Although there were impressive interbreed differences in circulating concentrations of T3, T4, IGF-I, and IGFBP, these were not related to differences in adult body size.

Increases in insulin-like growth factor binding protein-2 accompany decreases in proliferation and differentiation when porcine muscle satellite cells undergo multiple passages.

Subjecting cloned porcine myogenic satellite cells to multiple passages leads to decreased rates of cell division and myotube formation. Because IGF have been implicated in the regulation of muscle cell proliferation and differentiation, the present study was conducted to characterize secretion of IGF-I and IGF-binding proteins (IGFBP) in cultures of cloned porcine satellite cells at two stages of multiple passaging. To this end, we obtained a single porcine satellite cell clone that demonstrated relatively high capacities for cellular proliferation and differentiation into myotubes at the fifth passage but that had greatly diminished capacities for proliferation and myotube formation by the seventh passage. The predominant IGFBP secreted by this satellite cell clone was immunologically identified as IGFBP-2, and quantities of it were increased in medium from seventh-passage cultures. Quantities of IGF-I in medium were determined with a newly developed "titration" radioimmunoassay in which interference from IGFBP was minimized by adding a range of saturating quantities of IGF-II. Medium IGF-I concentrations in seventh-passage cultures were also increased relative to the fifth-passage cultures when expressed per unit of DNA. It is hypothesized that the observed increase of IGF-I in medium likely resulted from protective sequestration of IGF-I by IGFBP-2 rather than from enhanced IGF-I secretion. In summary, these data suggest that multiple passaging of cloned porcine satellite cells results in increased secretion of IGFBP-2, which is associated with depressed cell proliferation and myotube formation, perhaps because the increased IGFBP-2 sequestered IGF-I and reduced its bioactivity.

Feeding colostrum increases circulating insulin-like growth factor I in newborn pigs independent of endogenous growth hormone secretion.

Our objective was to examine the influence of feeding and endogenous GH secretion on circulating IGF-I in colostrum-deprived newborn pigs fed colostrum (n = 4), formula (control, n = 4), or water (n = 4). In another four formula-fed pigs, GH was ablated (GRF-A) with two intravenous injections of a GH releasing-factor antagonist (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2. Blood was serially sampled in all pigs to measure plasma IGF-I and GH profiles. Feeding increased plasma IGF-I concentration two- to fourfold and decreased GH secretion. Despite a more than 80% decrease in the plasma GH in GRF-A pigs, the circulating IGF-I concentration was similar to that in control pigs. In colostrum-fed pigs, plasma IGF-I was higher than that in control pigs, despite equal nutrient intake and lower circulating GH. There were no differences in plasma IGF binding protein (IGFBP)-3 levels among the treatment groups. However, the relative abundance of plasma IGFBP-4 was lower, and that of IGFBP-1 higher, in unfed pigs than in any of the three fed groups. The plasma insulin concentration was not different among fed pigs, but it was lower in unfed pigs. Our results indicate that the circulating IGF-I concentration is more dependent on nutrient intake than on GH in newborn pigs, despite relatively high GH concentrations. However, because the nutrient content in the formula was designed to match that of colostrum, a factor other than nutrient intake and GH was responsible for the maximal increase in circulating IGF-I concentration observed in colostrum-fed pigs.

Bioactivation of aflatoxin B1 in the nasal and tracheal mucosa in swine.

Whole-body autoradiography of 3H-labeled aflatoxin B1 in young pigs showed a localization of bound label in the nasal olfactory and respiratory mucosa, in the tracheo-laryngeal mucosa, and in the conjunctiva, in addition to the liver. Whole-body and microautoradiography also showed a labeling of pigmented tissues, which can be ascribed to a melanin binding of AFB1. In vitro experiments with microsomal preparations of various tissues from sows revealed that the nasal respiratory and olfactory mucosa had the highest capacity to form DNA-bound aflatoxin B1-metabolites. The tracheal mucosa and the liver, in order, had lesser binding capacity. The lung was found to be devoid of aflatoxin B1-bioactivating capacity. In vitro microautoradiography revealed bound label in specific cell types in the nose and trachea and in some cells of the conjunctiva. A drastic decrease in the aflatoxin B1-DNA binding was observed when microsomal preparations of the nasal respiratory and olfactory mucosa were incubated in the presence of reduced glutathione, but without any addition of cytosolic glutathione-S-transferases. In incubations of liver microsomes under these conditions a somewhat lower inhibition of the aflatoxin B1-DNA binding was seen. Our results demonstrate that the nasal olfactory and respiratory mucosa and the tracheal mucosa have a higher capacity than the liver to bioactivate aflatoxin B1 in swine. Our data further show that microsomal-associated glutathione-S-transferases with a high capacity to catalyze the conjugation of the reactive aflatoxin B1-epoxide to reduced glutathione are present in the nasal olfactory and respiratory mucosa of swine.

Intestinal nutrient-gene interaction: the effect of feed deprivation and refeeding on cholecystokinin and proglucagon gene expression.

We tested the hypothesis that dietary components reaching the bovine small intestine influence the expression of genes that encode the gastrointestinal neuropeptides cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The amount of digesta reaching the intestine was manipulated during the experiment by withholding feed from five heifers fitted with ruminal, duodenal, and ileal cannulas for 48 h and then subsequent refeeding. Duodenal and ileal biopsies were collected using a fiber-optic endoscope. A Northern hybridization procedure was used to evaluate changes in gene expression. Blood concentrations of CCK and GLP-1 were determined with RIA. The data indicate that CCK blood concentration and mRNA abundance decreased during the period of feed deprivation, but they returned to predeprivation values within 16 to 24 h of refeeding. The GLP-1 blood concentration also decreased during feed deprivation and returned to predeprivation values within 4 to 8 h of refeeding, despite the fact that proglucagon mRNA abundance did not change significantly during feed deprivation and refeeding. These findings provide evidence that CCK and GLP-1 are released in response to nutrients that reach the small intestine and may be involved in the physiological process of digestion and possibly play a role in regulating feed intake in ruminants.

Cultured porcine myogenic cells produce insulin-like growth factor binding protein-3 (IGFBP-3) and transforming growth factor beta-1 stimulates IGFBP-3 production.

Insulin-like growth factor binding proteins (IGFBP) may act locally as autocrine or paracrine regulators of insulin-like growth factor activity in specific tissues such as muscle. Although secretion of IGFBP by cultured myogenic cell lines has been examined, little is known about secretion of IGFBP by primary myogenic cell cultures. This may be because primary myogenic cultures contain non-muscle cells (fibroblasts) that complicate interpretation of IGFBP determinations. We have circumvented this problem by subculturing nonfusing cells from extensively fused porcine myogenic cultures and comparing the IGFBP production of these nonfusing, porcine muscle-derived cells with that of primary porcine myogenic cell cultures. Immunoprecipitation with specific antibodies and 125I-IGF-I ligand blot analysis showed that myogenic cultures secreted IGFBP-3 (doublet band, 43 kDa and 39 kDa), IGFBP-2 (34 kDa), IGFBP-4 (30 and 24 kDa), and IGFBP-5 (30 and 28 kDa). Muscle-derived fibroblasts secreted no detectable IGFBP-3 but approximately 10 times more IGFBP-2 than did myogenic cell cultures. Treatment of myogenic cultures for 24 h with transforming growth factor (TGF) beta-1 caused a concentration-dependent increase in IGFBP-3 secretion with a maximum 1.5-fold increase occurring at .5 ng of TGF beta-1/mL. In contrast, TGF beta-1 treatment did not stimulate detectable IGFBP-3 secretion by muscle-derived fibroblast cultures. Northern analysis of total RNA using a porcine IGFBP-3 probe revealed that TGF beta-1 treatment resulted in a fourfold increase in the steady-state level of IGFBP-3 mRNA in myogenic cultures. Insulin-like growth factor binding protein-3 mRNA was not detectable in fibroblast cultures either before or after TGF beta-1 treatment. This is the first report of IGFBP-3 secretion by cultured myogenic cells.

Compensatory growth in runt pigs is not mediated by insulin-like growth factor I.

Runt pigs grow more slowly and never reach the same body weight as age-matched littermates. We hypothesized that IGF-I would be reduced in the runts and that postnatal nutrition would alter IGF-I concentration and tissue expression. Runt and control littermates were removed from 20 crossbred sows 20 to 28 h after birth. Tissues were collected from a baseline group (n = 4). The remaining pigs were fed porcine milk replacer at either 70 or 120 g/kg BW for 14 d (n = 8). Feed intake and body weight were measured daily, with plasma samples collected by jugular venipuncture throughout the experiment. Expression of IGF-I mRNA was measured in the liver and gastrocnemius with an RNase protection assay. At d 0, runts were significantly smaller than controls in all measurements, except brain weight. During the 14 d, the relative rate of growth was significantly faster and more efficient in runts than in controls; however, runts never attained the same absolute body weight as controls. Circulating IGF-I was significantly reduced at d 0 but was similar to that in controls by d 2 of feeding. The IGF-I mRNA expression in liver or gastrocnemius muscle was not different between control and runts at d 0 or 14 and was not affected by dietary intake. This study has shown that runt pigs grow in a compensatory manner for at least the first 2 wk of life. However, this growth response does not seem to be mediated by IGF-I.