The influence of tropical adaptation on plasma concentrations of insulin-like growth factor-I in purebred and crossbred beef cattle.

In an effort to determine whether tropical adaptation influences circulating concentrations of the growth-related hormone IGF-I, 3-breed diallel matings were conducted using temperate Bos taurus (Angus), tropical Bos indicus (Brahman), and tropical Bos taurus (Romosinuano). Purebred Angus, Braham, and Romosinuano and crossbred Angus-Braham, Angus-Romosinuano, and Braham-Romosinuano heifers and steers were evaluated in 2 separate calf crops from 2003 and 2004. Blood samples were obtained from 10 heifers of each breed group (n = 90) for each year at weaning and on d 0 and 84 of postweaning trials. Samples were also taken from 10 steers of each breed group (n = 90) at weaning and on d 0 and 60 of individual finishing phase feeding trials for each year. Concentrations of IGF-I were determined by RIA. Analyses included effects of sire breed, dam breed, year of record, the age of the dam of the calf in years, and interactions. Age of calf in days was investigated as a linear and quadratic covariate. Separate analyses were conducted for steers and heifers. The direct effect of Angus was to reduce (P < 0.03) heifer concentrations of IGF-I at d 84 and in the repeated measures analysis. In the repeated measures analysis, the direct effect of Romosinuano was to increase concentrations of IGF-I (P = 0.01). Relative to the temperate Bos taurus breed, plasma concentrations of IGF-I were numerically greater in male and female tropically adapted breed groups.

Function of the corpus luteum in beef heifers is affected by acute submaintenance feeding but is not correlated with residual feed intake.

Seventy-four Angus and Angus × Hereford heifers were used in 2 successive years (yr 1, n = 43; yr 2, n = 31) to determine if luteal function of heifers during acute submaintenance feeding is related to variation in utilization of feed as determined by residual feed intake (RFI). Residual feed intake was determined for heifers beginning at 12.3 ± 0.1 mo of age in yr 1 and at 9.1 ± 0.1 mo of age in yr 2. Heifers were assigned to dry-lot pens (n = 6 to 9 heifers/pen) with electronic gates to measure individual feed intake of a total mixed ration for 70 and 72 d in yr 1 and 2, respectively. Residual feed intake was calculated as the difference between actual DMI and expected DMI from linear regression of DMI on mid-test BW(0.75) and ADG. At 14.4 ± 0.1 mo of age, all heifers were provided a restricted amount of feed to supply 40% of their maintenance energy requirements for 21 d. Estrous cycles of heifers were synchronized with PGF(2α) on d -10, 0, and 11 relative to start of restriction. Concentrations of progesterone in plasma on d 14 to 21 of restriction were used to determine if heifers ovulated. Overall ADG and ADFI were 0.83 ± 0.02 and 7.37 ± 0.67 kg/d, respectively, for yr 1; and 0.50 ± 0.02 and 5.66 ± 0.09 kg/d, respectively, for yr 2. There was no correlation between RFI and BW, ADG, ADFI, or ultrasound measure of backfat, nor was RFI related to concentrations of IGF-I in plasma. All heifers lost BW and had reduced backfat (P < 0.001) at the end of restricted feeding. All heifers had reproductive cycles before dietary restriction started. During acute nutritional restriction, 4 heifers became anovulatory. Sixteen heifers had concentrations of progesterone in plasma during restricted feeding that were atypical of normal luteal function. There was no relationship between luteal function during nutrient restriction and RFI of heifers. Circulating IGF-1 was greater at weaning and after restricted feeding in heifers with a smaller RFI (>0.5 SD below the mean) than heifers with a greater RFI (>0.5 SD above the mean). It is concluded that RFI is not related to luteal function during acute submaintenance feeding, but that short-term restriction of nutrient intake can alter luteal function that may compromise fertility, even in heifers that exhibit estrus and ovulate.

Mtbp haploinsufficiency in mice increases tumor metastasis.

Mdm2 inhibits the function of the p53 tumor suppressor. Mdm2 is overexpressed in many tumors with wild-type p53 suggesting an alternate mechanism of loss of p53 activity in tumors. An Mdm2-binding protein (MTBP) was identified using a yeast two-hybrid screen. In tissue culture, MTBP inhibits Mdm2 self-ubiquitination, leading to stabilization of Mdm2 and increased degradation of p53. To address the role of MTBP in the regulation of the p53 pathway in vivo, we deleted the Mtbp gene in mice. Homozygous disruption of Mtbp resulted in early embryonic lethality, which was not rescued by loss of p53. Mtbp+/- mice were not tumor prone. When mice were sensitized for tumor development by p53 heterozygosity, we found that the Mtbp+/-p53+/- mice developed significantly more metastatic tumors (18.2%) as compared to p53+/- mice (2.6%). Results of in vitro migration and invasion assays support the in vivo findings. Downmodulation of Mtbp in osteosarcoma cells derived from p53+/- mice resulted in increased invasiveness, and overexpression of Mtbp in Mtbp+/-p53+/- osteosarcoma cells inhibited invasiveness. These results suggest that MTBP is a metastasis suppressor. These results advance our understanding of the cellular roles of MTBP and raise the possibility that MTBP is a novel therapeutic target for metastasis.