Acute handling disturbance modulates plasma insulin-like growth factor binding proteins in rainbow trout (Oncorhynchus mykiss)

The effects of acute stressor exposure on proximal (growth hormone [GH]) and distal (insulin-like growth factor-I [IFG-I] and insulin-like growth factor-binding proteins [IFGBPs]) components of the somatotropic axis are poorly understood in finfish. Rainbow trout (Oncorhynchus mykiss) were exposed to a 5-min handling disturbance to mimic an acute stressor episode, and levels of plasma GH, IGF-I, and IGFBPs at 0, 1, 4, and 24 h post-stressor exposure were measured. An unstressed group was also sampled at the same clock times (09:00, 10:00, 13:00, and 08:00 [the following day]) as acute stress sampling to determine temporal changes in the above somatotropic axis components. The acute stressor transiently elevated plasma cortisol and glucose levels at 1 and 4 h post-stressor exposure, whereas no changes were seen in the unstressed group. Plasma GH levels were not affected by handling stress or sampling time in the unstressed animals. Plasma IGF-I levels were significantly depressed at 1 and 4 h post-stressor exposure, but no discernible temporal pattern was seen in the unstressed animals. Using a western ligand blotting technique, we detected plasma IGFBPs of 21, 32, 42, and 50 kDa in size. The plasma levels of the lower-molecular-weight IGFBPs (21 and 32 kDa) were unaffected by handling stressor, nor were there any discernible temporal patterns in the unstressed animals. By contrast, the higher-molecular-weight IGFBPs (42 and 50 kDa) were affected by stress or time of sampling. Levels of the 42-kDa IGFBP levels significantly decreased over the sampling period in unstressed control animals, but this temporal drop was eliminated in stressed animals. Levels of the 50-kDa IGFBPs also decreased significantly over the sampling time in unstressed trout, whereas handling disturbance transiently increased levels of this IGFBP at 1 h but not at 4 and 24 h post-stressor exposure compared with the control group. Overall, our results suggest that acute stress adaptation involves modulation of plasma IGF-1 and high-molecular-mass IGFBP levels (42 and 50 kDa) in rainbow trout.     

Estimation of (co)variance components for reproductive traits in Angus beef cattle divergently selected for blood serum IGF-I concentration

The objective of this study was to obtain estimates of (co)variance components for reproductive traits and insulin-like growth factor-I (IGF-I) concentration. Data were from a divergent selection experiment for blood serum IGF-I concentration in Angus beef cattle. Numbers of observations for mean IGF-I concentration of three blood samples taken at d 28, 42, and 56 of the 140-d postweaning test, scrotal circumference (SC), percentage of motile sperm cells (PMSC), percentage of morphologically normal sperm cells (PNSC), age of heifers at first calving (AFC), and calving rate (CR) were 1,848, 825, 596, 765, 294, and 2,092, respectively. Total number of animals in the numerator relationship matrix, including base animals, was 2,864, of which 1,861 were inbred. Estimates of direct heritability for IGF-I concentration of three blood samples collected at d 28, 42, and 56 of the postweaning test and for mean IGF-I concentration were 0.43+/-0.08, 0.51+/-0.09, 0.41+/-0.08, and 0.50+/-0.08, respectively. Estimates of direct heritability for SC, PMSC, PNSC, AFC, and CR were 0.51+/-0.13, 0.08+/-0.12, 0.47+/-0.07, 0.26+/-0.28, and 0.11+/-0.05, respectively. With the exception of age at first calving, estimates of maternal heritability and proportion of phenotypic variance that were due to permanent environmental effects of the dams were smaller than 0.21. Observations for calving rate were entered as either 1 (if calved) or 100 (if not calved). Estimates of additive genetic correlations of mean IGF-I concentration with SC, PMSC, PNSC, AFC, and CR were 0.35+/-0.11, 0.43+/-0.32, 0.00+/-0.03, -0.14+/-0.33, and -0.41+/-0.16, respectively. Environmental and phenotypic correlations for all of the traits with IGF-I measurements were smaller than 0.23. These results suggest that selection for increased serum IGF-I concentration should result in increased scrotal circumference, percent motile sperm cells, and calving rate.     

Genetic parameter estimates for serum insulin-like growth factor I concentrations, and body weight and weight gains in Angus beef cattle divergently selected for serum insulin-like growth factor I concentration

Data for the current study were obtained from a divergent selection experiment in which the selection criterion was the average serum IGF-I concentrations of 3 postweaning blood samples collected from purebred Angus calves. Multiple-trait derivative-free REML procedures were used to obtain genetic parameter estimates for IGF-I concentrations and for BW and BW gains measured from birth to the conclusion of a 140-d postweaning performance test. Included in the analysis were 2,674 animals in the A(-1) matrix, 1,761 of which had valid records for IGF-I concentrations. Direct heritability estimates +/- SE for IGF-I concentration at d 28, 42, and 56 of the postweaning period and for mean IGF-I concentrations were 0.44 +/- 0.07, 0.51 +/- 0.08, 0.42 +/- 0.07, and 0.52 +/- 0.08, respectively. Heritability estimates for maternal genetic effects ranged from 0.10 +/- 0.05 to 0.20 +/- 0.06. The proportion of total phenotypic variance due to the maternal permanent environmental effect was essentially zero for all measures of IGF-I concentrations. Genetic correlations of IGF-I concentrations with weaning and post-weaning BW ranged from 0.07 +/- 0.12 to 0.32 +/- 0.11 and generally demonstrated an increasing trend during the postweaning period. Averaged across the various measures of IGF-I, the genetic correlation of IGF-I with preweaning gain was 0.14, whereas the genetic correlation with postweaning gain was 0.29. Genetic correlations between IGF-I and BW gain were positive during all time intervals, except between weaning and the beginning of the postweaning test and from d 84 to 112 of the postweaning period. Environmental and phenotypic correlations of IGF-I with BW and BW gains were generally positive, but small. These results indicate that postweaning serum IGF-I concentration is moderately to highly heritable and has small positive genetic, environmental, and phenotypic correlations with BW other than birth weight and with pre- and postweaning gain. Therefore, if IGF-I proves to be a biological indicator of an economically important trait (e.g., efficiency of feed use for growth) in beef cattle, it should be possible to rapidly change IGF-I concentrations via selection without significantly altering live weight or rate of gain.     

Immunolocalization of insulin-like growth factor-I (IGF-I) and its receptors (IGF-IR) in the equine epididymis

Insulin-like growth factor plays a paracrine/autocrine role in regulating testicular function in the stallion, but its presence in the equine epididymis remains unknown. The aim of this study was to test the hypothesis that insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) are localized in the caput, corpus, and cauda of the epididymis in an age-dependent manner. Immediately after castration, epididymal tissue was fixed, paraffin-embedded, and processed for immunohistochemistry (IHC). Western blot was also performed using equine epididymal extracts to verify the specificity of the antibodies against IGF-I and IGF-IR. Immunolabeling of IGF-I was observed in the cytoplasm of principal and basal cells in the caput, corpus, and cauda at the pre-pubertal (3–7 months), pubertal (12–18 months), post-pubertal (2–4 years), and adult stages (4.5–8 years). Immunolabeling of IGF-IR was observed in the cytoplasm of principal cells in all regions of the epididymis in each age group. Immunolabeling of IGF-IR was also detected in the cytoplasm of basal cells from animals of all ages. Bands observed by Western blot corresponded to the molecular weights of IGF-I and IGF-IR, ~23 kDa and 95 kDa, respectively. These results suggest that IGF-I might function as an autocrine and/or paracrine factor during the development, maintenance and/or secretions of the stallion epididymis.     

Effect of growth hormone administration to mature miniature Brahman cattle treated with or without insulin on circulating concentrations of insulin-like growth factor-I and other metabolic hormones and metabolites

Previously, we determined that a primary cause of proportional stunted growth in a line of Brahman cattle was related to an apparent refractoriness in metabolic response to GH in young animals. The objective of this study was to determine the effect of administration of GH, insulin (INS), and GH plus INS to mature miniature Brahman cows (n = 6; 9.7 ± 2.06 y; 391 ± 48.6 kg) and bulls (n = 8; 9.4 ± 2.00 y; 441 ± 54.0 kg) on circulating concentrations of metabolic hormones and metabolites, primarily IGF-I and IGF-I binding proteins. We hypothesized that IGF-I secretion could be enhanced by concomitant administration of exogenous GH and INS, and neither alone would be effective. Animals were allotted to a modified crossover design that included four treatments: control (CON), GH, INS, and GH + INS. At the start of the study, one-half of the cattle were administered GH (Posilac; 14-d slow release) and the other one-half served as CON for 7 d. Beginning on day 8, and for 7 d, INS (Novolin L) was administered (0.125 IU/kg BW) twice daily (7:00 AM and 7:00 PM) to all animals; hence, the INS and GH + INS treatments. Cattle were rested for 14 d and then were switched to the reciprocal crossover treatments. Blood samples were collected at 12-hour intervals during the study. Compared with CON, GH treatment increased (P < 0.01) mean plasma concentrations of GH (11.1 vs 15.7 ± 0.94 ng/mL), INS (0.48 vs 1.00 ± 0.081 ng/mL), IGF-I (191.3 vs 319.3 ± 29.59 ng/mL), and glucose (73.9 vs 83.4 ± 2.12 mg/dL) but decreased (P < 0.05) plasma urea nitrogen (14.2 vs 11.5 ± 0.75 mg/dL). Compared with INS, GH + INS treatment increased (P < 0.05) mean plasma concentration of INS (0.71 vs 0.96 ± 0.081 ng/mL), IGF-I (228.7 vs 392.3 ± 29.74 ng/mL), and glucose (48.1 vs 66.7 ± 2.12 mg/dL), decreased (P < 0.01) plasma urea nitrogen (13.6 vs 10.4 ± 0.76 mg/dL), and did not affect GH (13.5 vs 12.7 ± 0.95 ng/mL). In the miniature Brahman model, both the GH and GH + INS treatments dramatically increased circulating concentrations of IGF-I in mature cattle, suggesting that this line of Brahman cattle is capable of responding to bioactive GH.     

Evaluation of interference by insulin-like growth factor I (IGF-I) binding proteins in a radioimmunoassay for IGF-I in serum from dairy cows.

Insulin-like growth factor I (IGF-I) circulates in serum bound to a number of different binding proteins (BPs). With antibodies currently available, BPs must be dissociated and inactivated or removed from serum prior to measurement of IGF-I by radioimmunoassay (RIA). Serum samples which spanned a 13-fold range in IGF-I concentration were obtained from lactating dairy cows and used to develop conditions for assay of IGF-I with minimal interference from BPs. Removal of BPs from serum by acid-ethanol extraction resulted in interference in the RIA. Therefore, serum was incubated with 0.1 M glycyl-glycine HCl to inactivate BPs as suggested by Underwood et al. Time, temperature and pH were optimum when serum was incubated for 48 hr at 37 C, pH 3.7. Binding protein inactivation was evaluated by ability of glycyl-glycine incubated serum to reassociate with 125I-IGF-I. In addition, BPs isolated by gel filtration of glycyl-glycine incubated serum were tested for interference in the RIA. The concentration of IGF-I in serum where inactivated BPs were removed by acid gel filtration was compared to corresponding glycyl-glycine incubated serum. There was a 1:1 relationship which intersected at zero indicating that total IGF-I could be measured. Therefore, incubation of serum with glycyl-glycine is a reliable method for measuring total IGF-I in serum from dairy cows.     

Low-density lipoprotein-related receptor protein 1 (LRP-1) is not required for insulin-like growth factor binding protein 3 (IGFBP-3) to suppress L6 myogenic cell proliferation

Insulin-like growth factor binding protein-3 (IGFBP-3) suppresses proliferation of numerous cell types, including myogenic cells, via both insulin-like growth factor (IGF)-dependent and IGF-independent mechanisms; however, the mechanism of IGF-independent suppression of proliferation is not clearly defined. In nonmuscle cells, binding of IGFBP-3 to the low-density lipoprotein receptor-related protein-1 (LRP-1)/activated α(2)M receptor is reportedly required for IGFBP-3 to inhibit proliferation. These findings suggest that binding to this receptor also may be required for IGFBP-3 to suppress proliferation of cultured myogenic cells. To investigate the role of the LRP-1 receptor in suppression of myogenic cell proliferation by IGFBP-3, we have examined the effect of receptor-associated protein, an LRP-1 receptor antagonist, on recombinant porcine (rp)IGFBP-3 inhibition of L6 myogenic cell proliferation. Treatment with receptor-associated protein results in a 37% decrease (P < 0.05) in the ability of rpIGFBP-3 to inhibit L6-cell proliferation. In L6 cells subjected to LRP-1 small interfering RNA treatment for 48 h (LRP-1 silenced), LRP-1 mRNA levels were reduced by greater than 80% compared with control cultures treated with nonsense small interfering RNA (mock silenced). In addition, the 85-kDa transmembrane subunit of LRP-1 was undetectable in Western immunoblots of total protein lysates from LRP-1-silenced cells. Even though LRP-1 mRNA and protein levels were dramatically reduced in LRP-1-silenced L6 cells compared with mock-silenced controls, rpIGFPB-3 suppressed proliferation rate to the same extent in both LRP-1-silenced and mock-silenced cultures. Our results strongly suggest that, in contrast to data obtained for nonmuscle cell lines, the LRP-1 receptor is not required for IGFBP-3 to suppress proliferation of L6 myogenic cells.     

Follicular fluid concentrations of free insulin-like growth factor (IGF)-I during follicular development in mares

The objective of the present study was to evaluate changes in concentrations of free insulin-like growth factor (IGF)-I in follicular fluid (FFL) during follicle development in the mare. Mares (n = 14) were classified as either in the follicular phase (n = 8) or luteal phase (n = 6). Follicles (n = 92) were categorized as small (6–15 mm; n = 54), medium (16–25 mm; n = 23) or large (>25 mm; n = 15) and FFL was collected. Free IGF-I levels in FFL in large follicles of follicular phase mares were greater (P < 0.05) than in large follicles of luteal phase mares and small or medium follicles of luteal and follicular phase mares. Free IGF-I concentrations were greater (P < 0.05) in large follicles of luteal phase mares than small but not medium follicles of luteal phase mares. FFL ratio of estradiol:progesterone paralleled changes in free IGF-I. Free IGF-I concentrations were negatively correlated (P < 0.05) with insulin-like growth factor binding protein (IGFBP)-2, -4 and -5 but not IGFBP-3 levels. In addition, free IGF-I concentrations in FFL were positively correlated (P < 0.01) with FFL estradiol, progesterone, androstenedione, estradiol:progesterone ratio, total IGF-I and total IGF-II. We conclude that increases in intrafollicular levels of bioavailable (free) IGF-I are associated with increased steroidogenesis in developing mare follicles.     

Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs

BackgroundSerum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets.ObjectivesThis study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors.MethodsThe serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA).ResultsThe ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5–175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5–79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2–57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6–70.5]) in healthy dogs.ConclusionsThe serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.     

Inhibitory effect of insulin-like growth factor-binding protein-7 (IGFBP7) on in vitro angiogenesis of vascular endothelial cells in the rat corpus luteum

Angiogenesis in the developing corpus luteum (CL) is a prerequisite for establishment and maintenance of an early pregnancy. To explore the physiological significance of insulin-like growth factor-binding protein-7 (IGFBP7) in the developing CL, the effects of IGFBP7 on vascular endothelial growth factor (VEGFA)- and luteinizing hormone (LH)-induced in vitro tube formation were tested using isolated luteal microvascular endothelial cells (LECs). Capillary-like tube formation of LECs and their proliferation were stimulated by both VEGFA and LH. IGFBP7 treatment suppressed VEGFA- or LH-induced tube formation. The proliferation and migration of LECs, and phosphorylation of mitogen-activated protein kinase kinase and extracellular signal-regulated kinase 1/2 were inhibited by IGFBP7. Furthermore, IGFBP7 attenuated VEGFA-enhanced cyclooxygenase (COX)-2 mRNA expression and prostaglandin E₂ secretion. These findings suggest the possibility that luteal IGFBP7 secretion may suppress the stimulatory effect of VEGFA on angiogenesis in the early CL.     

The role of endocrine insulin-like growth factor-I (IGF-I) in female bovine reproduction

Insulin-like growth factor-I (IGF-I) plays a pivotal role in cattle fertility, acting as a monitoring signal that allows reproductive events to occur when nutritional conditions for successful reproduction are reached. However, endocrine IGF-I is not a predictor of reproductive events, but rather an indirect estimator of the suitability of the animal to achieve the reproductive event in question. Although measuring circulating IGF-I concentrations might not have any clinical application in the cattle industry, endocrine IGF-I screening will continue to be important for the study of interactions between nutrition and reproduction. In addition, endocrine IGF-I screening could be used as an ancillary test for the selection of cattle for high reproductive potential, especially in herds of high genetic merit for milk production, in which a decline in fertility has been identified.     

Change of plasma insulin-like growth factor-1 (IGF-1) concentration with early growth in Japanese beef cattle

The aim of the present study was to examine the change in plasma insulin‐like growth factor‐1 (IGF‐1) concentration with early growth, changes of bodyweight (BW) and relative dairy gain (RDG) in the pre‐ (PRW) and postweaning periods (POW) in Japanese beef cattle, and relationships with metabolites. A total of 33 calves, 22 Japanese black, 6 Japanese shorthorn and 5 of their crossbreed were studied. Insulin‐like growth factor‐1 and metabolite (glucose, triacylglycerol, nonesterified fatty acid) levels in the plasma, from jugular vein blood taken every month, were measured along with BW. Insulin‐like growth factor‐1 in POW increased dramatically with increase of BW (P < 0.05), and the correlation was positive at 0.52 (P < 0.01). Glucose levels correlated significantly with BW, RDG and IGF‐1 (P < 0.01). Metabolic required calorie correlated positively with IGF‐1 (P < 0.01). Also, correlations of BW in POW, with BW and RDG in PRW were positive (P < 0.01). Growth in PRW would be influenced by maternal effects, while active self‐secretion of IGF‐1 in POW might contribute to POW growth. These factors suggested that to increase growth in PRW, maintaining enough maternal effect and IGF‐1 level in POW, was important for establishing better growth after weaning.     

Association of single nucleotide polymorphisms in the growth hormone and growth hormone receptor genes with blood serum insulin-like growth factor I concentration and growth traits in Angus cattle

This study was conducted to identify polymorphisms in the promoter and coding regions of the bovine growth hormone and growth hormone receptor genes and to study association of polymorphisms identified in these genes with growth traits and serum insulin-like growth factor-I (IGF-I) concentration. The denaturing gradient gel electrophoresis method and sequencing were utilized to identify three new single nucleotide polymorphisms in the promoter region of the growth hormone gene in Angus cattle. Polymerase chain reaction-based restriction fragment length polymorphism procedures were developed for rapid determination of the single nucleotide polymorphism genotypes in the growth hormone and the growth hormone receptor genes among Angus calves from lines divergently selected for high or low blood serum IGF-I concentration. The IGF-I concentration and growth traits were analyzed using animal models. The single nucleotide polymorphism in the promoter region of the growth hormone receptor gene was associated with serum IGF-I concentration on d 42 of the postweaning test and with mean IGF-I concentration. The associated effects of the markers need to be verified in other populations.     

Effect of feed restriction on serum somatotropin, insulin-like growth factor-I-(IGF-I) and IGF binding proteins in cyclic heifers actively immunized against growth hormone releasing factor

Feed restriction often increases serum somatotropin (ST) and decreases insulin-like growth factor-I (IGF-I) in ruminants; however, the mechanisms responsible for this change in ST and IGF-I are not well defined. We investigated the effects of feed restriction on serum ST, IGF-I, IGF binding proteins (IGFBP), insulin and nonesterified fatty acids (NEFA) in cyclic Angus and Charolais heifers (n=15) previously immunized against growth hormone releasing factor (GRFi) or human serum albumin (HSAi). Cows were fed a concentrate diet ad libitum (AL) or were restricted to 2 kg cotton seed hulls (R) for 4 d. Each heifer received each dietary treatment in a single reversal design. As anticipated, GRFi decreased ST, IGF-I and insulin (P<.05). In addition, GRFi decreased serum IGFBP-3 (P<.01), but increased IGFBP-2 (P<.01). Feed restriction resulted in an increase in serum ST in HSAi, but not in GRFi heifers. Regardless of immunization treatment, feed restriction decreased serum IGF-I and insulin, and increased NEFA (P<.01). In conclusion, the increase in serum ST levels observed during feed restriction was blocked by active immunization against GRF. However, feed restriction resulted in decreased serum IGF-I in GRFi heifers in spite of initial low levels of IGF-I (due to GRFi). Although GRFi decreased levels of IGFBP-3 and increased levels of IGFBP-2, feed restriction for 4 d did not alter serum IGFBP.     

Comparison of insulin-like growth factor I serum binding proteins in sheep and cattle: species differences in size and endogenous binding capacities

Binding proteins (BP) for insulin-like growth factor I (IGF-I) were characterized in sheep and beef cattle serum for molecular weight (Mr) and binding characteristics. Serum was incubated with [125I] IGF-I at 37 degrees C before chromatography over a 1.6-cm X 94.0-cm column of Sephacryl S-300 (pH 7.4, 4 degrees C). Beef serum exhibited a 145 k Mr (mol. wt X 1,000) and a 35 to 39 k Mr BP. Sheep serum possessed a 170 to 190 k and a 35 to 38 k Mr protein. Binding of [125I] IGF-I was inhibited in the presence of excess unlabeled ovine somatomedin, demonstrating specific binding for each BP of both species. The high Mr component was pituitary-dependent in sheep, as evidenced by binding patterns from serum of hypophysectomized sheep. Direct binding studies of the Sephacryl-separated BP demonstrated that the native BP of high molecular weight of both species bound only minor amounts of [125I] IGF-I in a manner unrelated to BP concentration. The BP of low molecular weight of beef cows displayed a bell-shaped dose-response binding curve with maximum binding at 250 micrograms/ml BP, whereas binding to sheep BP of low molecular weight was independent of BP concentration. After chromatography on Sephadex G50 at pH 2.8, both BP from both species exhibited concentration-dependent binding that plateaued at 250 to 500 micrograms/ml of BP of low molecular weight but was curvilinear for the BP of high molecular weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of weaning at different ages on serum insulin-like growth factor I (IGF-I), IGF binding proteins and serum in vitro mitogenic activity in swine.

We investigated the effects of weaning or fasting of 21- or 35-d-old swine by monitoring serum mitogenic activity, circulating insulin-like growth factor I (IGF-I) and its binding proteins using L6 myoblast bioassays, RIA and ligand blotting techniques. Serum samples were collected from 21- or 35-d-old animals just before and 36 h after weaning or fasting. Sera from 21- and 35-d-old weaned animals were not significantly altered in their ability to promote myoblast proliferation, whereas sera from 21- and 35-d-old fasted animals caused 29 and 21% decreases (P less than .05) compared with preweaning. The mitogenic activity of control serum was inhibited by serum from fasted animals but not by preweaned or weaned sera. Serum IGF-I levels were decreased 65 to 70% (P less than .05) with weaning or fasting at both ages. Unoccupied binding sites on circulating IGF binding proteins in the 155 kDa range decreased 18 to 19% with weaning at both ages and decreased 40% (P less than .05) with fasting at 21 d but only 17% at 35 d. Ligand blotting revealed that the 43 and 39 kDa IGF binding protein bands decreased with weaning and fasting at both ages, whereas the 29-kDa band increased with weaning and fasting. These data indicate that serum IGF-I and specific IGF binding protein bands decrease during weaning or fasting at 21 and 35 d of age. However, serum mitogenic activity did not always follow serum IGF-I levels.     

Antepartal insulin-like growth factor concentrations indicating differences in the metabolic adaptive capacity of dairy cows

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I^high or IGF-I^low), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 ± 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I^high cows compared to IGF-I^low cows. Estradiol concentration tended to be greater in the IGF-I^low group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.     

The effect of exogenous insulin-like growth factor-I (IGF-I) on the reproductive performance of female rats, and on serum concentrations of endogenous IGF-I and IGF-I binding proteins.

The effect of exogenous IGF-I on the reproductive performance of female rats was examined by infusing either recombinant human IGF-I (400 micrograms/d; n = 19) or vehicle (n = 18) over a four-day period (the time of one reproductive cycle) beginning on the day following estrus. The females were exposed to male rats one day after the infusions had commenced, and were euthanized 15 d later. There was no treatment effect on serum progesterone levels at this time or on the number of fetuses. Furthermore, the number of corpora lutea were not different between the IGF-I and vehicle infused groups (15.8 vs. 14.8; P = 0.09). Total serum IGF-I concentrations, as determined with a polyclonal antiserum based RIA, were increased approximately three-fold in samples obtained 20 hr after commencing the IGF-I infusion. These samples were also analyzed for IGF-I with a monoclonal antibody based RIA previously shown to detect human, but not rat, IGF-I. By subtraction, the concentration of endogenous rat IGF-I was found to be approximately 60% higher in IGF-I-infused rats than in control rats. This increase was likely due to a reduced clearance rate of IGF-I from the circulation, caused by a marked induction of 42-46 kDa and 30-34 kDa IGF-I binding proteins observed in these samples with a ligand blot technique. The binding protein induction indicates that the infused IGF-I was bioactive. This induction may have attenuated the effects of IGF-I on ovarian function.     

Genetic parameter estimates for serum insulin-like growth factor-I concentration and ultrasound measurements of backfat thickness and longissimus muscle area in Angus beef cattle

A divergent selection experiment for serum IGF-I concentration began at the Eastern Ohio Resource Development Center in 1989 using 100 spring-calving (50 high line and 50 low line) and 100 fall-calving (50 high line and 50 low line) purebred Angus cows. Following weaning, bull and heifer calves were fed in drylot for a 140-d period. Real-time ultrasound measurements of backfat thickness and longissimus muscle area were taken on d 56 and 140 of the postweaning test. Only ultrasound data from calves born from fall 1995 through spring 1999 were included in the analysis. At the time of this study, IGF-I measurements were available for 1,521 bull and heifer calves, and ultrasound data were available for 636 bull and heifer calves. Data were analyzed by multiple-trait, derivative-free, restricted maximum likelihood methods. Estimates of direct heritability for IGF-I concentration at d 28, 42, and 56 of the postweaning period, and for mean IGF-I concentration were 0.26 +/- 0.07, 0.32 +/- 0.08, 0.26 +/- 0.07, and 0.32 +/- 0.08, respectively. Direct heritabilities for ultrasound estimates of backfat thickness ranged from 0.17 +/- 0.11 to 0.28 +/- 0.12, whereas direct heritabilities for longissimus muscle area ranged from 0.20 +/- 0.10 to 0.36 +/- 0.12, depending on the time of measurement and the covariate used for adjustment (age vs. weight). Direct genetic correlations of IGF-I concentrations with backfat thickness at d 56 and 140 and with longissiumus muscle area at d 56 and 140 averaged 0.02, 0.20, -0.08, and 0.23, respectively, when age was used as the covariate for both IGF-I and ultrasound measurements. Corresponding genetic correlations when age was used as the covariate for IGF-I and weight was used as the covariate for ultrasound measurements were 0.05, -0.07, -0.22, and -0.04, respectively. Therefore, the positive associations of serum IGF-I concentration with backfat thickness and longissimus muscle area at d 140 seem to have been partially mediated by weight. Results of this study do not indicate strong associations of serum IGF-I concentration with fat thickness or muscling of bulls and heifers during the postweaning feedlot period.