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Differential tissue regulation of the insulin-like growth factors in rats bearing the MStT/W15 pituitary tumor.

The content of insulin-like growth factors, IGF-I and IGF-II, was measured in tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15. Serum IGF-I was elevated in tumor-implanted rats [2,557 +/- (SE) 419 vs. 891 +/- 100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 +/- 16 ng/g) in comparison to control liver tissue (160 +/- 5 ng/g) or control pituitary (80 +/- 3 ng/g). The IGF-I levels were significantly increased in most peripheral tissues in the tumor-bearing rats with the exception of the liver. In support of this finding, messenger RNA for prepro IGF-I was likewise not increased in the livers of tumor-bearing rats, nor was there an increase in the growth hormone-dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All tumors had detectable levels of prepro IGF-I mRNA which was, however, less than 50% of that noted in normal control liver. The tumors also expressed an IGF-BP which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF-II were similar in control and tumor-bearing animals (approximately 70 ng/ml). IGF-II levels in the tumor (90 +/- 5 ng/g) were significantly higher than levels in control liver (34 +/- 2 ng/g), but similar to those found in normal pituitary (165 +/- 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively increased in skeletal muscle and heart of tumor-bearing rats. These data demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the liver does not appear to be stimulated over control levels by high serum growth hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are increased in livers of tumor-bearing rats. This suggests that the increase in serum IGF-I in these animals is due to increased production of IGF-I by the tumors themselves and by nonhepatic peripheral tissues and further that hepatic responsiveness to growth hormone is diminished in these tumor-bearing animals.

Animals↗

Adenine nucleotide translocase, Na+-K+-and Mg2+-ATPases and differential tissue response to hypothyroidism.

The activities of adenine nucleotide translocase (ANT), Na+-K+-ATPase (EC 3.6.1.3) and Mg2+-ATPase (EC 3.6.1.3) together with mitochondrial marker enzymes, succinic dehydrogenase (EC 1.3.99.1) and glutamate dehydrogenase (EC 1.4.1.2), were measured in liver, kidney, brain and testis from normal and thyroidectomised rats. Na+-K+-ATPase decreased by approximately 50% in liver and kidney; ANT decreased only in liver (-40%) while the activity of ANT per gram kidney increased by 38%. The activity of Mg2+-ATPase closely correlated with the pattern of change of ANT. The hormonal and substrate regulation of ANT is discussed in relation to its role in the regulation of intracellular phosphate potential and compartmentation in liver and kidney.

Adenosine Triphosphatases↗

Edge detection in ultrasound images based on differential tissue attenuation rates.

Identification of the cardiac borders is a basic goal in the analysis of echocardiographic images. This is a requirement for various analysis purposes, such as the derivation of quantitative parameters, for wall motion analysis and for the creation of three-dimensional reconstructions. Border identification is usually accomplished by first identifying a set of generic edge points, then extracting the border of interest from the edge map. A variety of edge detection algorithms have been reported in the literature. However, the most commonly used methods are all based on the same underlying tissue discriminant, namely, the widely differing backscatter levels of the different types of tissue that form the cardiac borders, in particular, blood and myocardium. We have implemented a new method of edge detection based on an entirely different ultrasonic tissue characteristic--that of attenuation, the rate at which the tissue absorbs ultrasonic energy. This characteristic also differs widely between blood and myocardium, and therefore provides an alternative means of discriminating between these two types of tissue. The method searches for the abrupt change in attenuation rate that characteristically occurs at the blood/myocardium interface. At each point in the image, the average attenuation rates of the portions of tissue radially preceding and radially following the point are determined by least-squares regression. If one of these attenuation rates is sufficiently close to that of blood, and the other is sufficiently close to that of myocardium, then the point is flagged as an edge point. This paper describes how this method is implemented in software, and presents the results of applying the method to a library of sample images.

Algorithms↗

Differential tissue regulation of insulin-like growth factor-I content and binding proteins after endotoxin.

The purpose of the present study was to investigate the regulation of plasma and tissue levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-1, -2, and -3 (IGFBP-1, -2, and -3) in rats injected with Escherichia coli lipopolysaccharide (LPS), a component of the outer cell wall of gram-negative bacteria. When injected iv into conscious overnight fasted rats, plasma IGF-I levels were initially decreased within 1 h, maximally depressed at 4 h, and still only 35-45% of control values at 24 h. GH levels were reduced as early as 30 min after LPS, averaged 80-90% of control values between 1-4 h, but had returned to basal levels by 24 h. The magnitude and duration of these changes were similar regardless of whether 100 or 10 micrograms/100 g BW (LD20 and LD0, respectively) LPS were injected. Plasma levels of IGFBP-1 and a 28K mol wt BP (BP-28K) were elevated 2- to 3-fold 4 h after LPS treatment, whereas IGFBP-3 and -2 levels were unchanged. The elevation in plasma IGFBP-1 and IGFBP-28K was observed as early as 1 h and was sustained for up to 24 h after LPS treatment. IGF-I levels were decreased 30-50% in liver, pituitary, and skeletal muscle, unchanged in brain, and elevated 5-fold in kidney in response to LPS. Of the tissues sampled, IGFBP-3 and -2 were selectively elevated in liver after LPS treatment. IGFBP-1 was increased in liver, muscle, and kidney in response to LPS. The level of the 28,000 mol wt BP was increased in liver (83%) and not changed in muscle or brain. These data indicate that LPS produces both rapid and sustained alterations in circulating levels of GH, IGF-I, and IGFBPs. Furthermore, there were marked tissue-specific changes in levels of IGF-I and IGFBPs. LPS-induced changes in plasma and tissue IGFBP-3 were not regulated by changes in GH, and changes in insulin could not explain the alterations in IGFBP-1 and -2. These results suggest that after the injection of LPS, changes in IGF-I and IGFBP levels are regulated by a mechanism(s) different from those previously described.

Animals↗

Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.

In humans, the biotransformation of cholesterol and its hydroxylated metabolites (oxysterols) by sulfonation is a fundamental process of great importance. Nevertheless, the sulfotransferase enzyme(s) that carries out this function has never been clearly identified. Cholesterol is a relatively poor substrate for the previously cloned hydroxysteroid sulfotransferase (HST), i.e. dehydroepiandrosterone (DHEA) sulfotransferase (HST1). Recently, cloning of a single human gene that encodes for two proteins related to HST1 was reported. These newly cloned sulfotransferases (HST2a and HST2b), while exhibiting sequence similarity to other members of the soluble sulfotransferase superfamily, also contain unique structural features. This latter aspect prompted an examination of their substrate specificity for comparison with HST1. Thus, HST1, HST2a, and HST2b were overexpressed as fusion proteins and purified. Furthermore, a novel procedure for the isolation of cholesterol and oxysterol sulfonates was developed that was used in association with HPLC to resolve specific sterol sulfonates. HST1 preferentially sulfonated DHEA and, to a lesser extent, oxysterols; whereas cholesterol was a negligible substrate. The reverse, however, was the case for the HST2 isoforms, particularly HST2b, which preferentially sulfonated cholesterol and oxysterols, in contrast to DHEA, which served as a poor substrate for this enzyme. RT-PCR analysis revealed distinct patterns of HST1, HST2a, and HST2b expression. It was particularly notable that both HST2 isoforms, but not HST1, were expressed in skin, a tissue where cholesterol sulfonation plays an important role in normal development of the skin barrier. In conclusion, substrate specificity and tissue distribution studies strongly suggest that HST2a and HST2b, in contrast to HST1, represent normal human cholesterol and oxysterol sulfotransferases. Furthermore, this study represents the first example of the sulfonation of oxysterols by a specific human HST.

Amino Acid Sequence↗

Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat.

The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Comparative study of the repeated nucleotide sequences in DNA from differentiated tissues and tumors].

DNA renaturation kinetics was measured for the genomes of normal (spleen) and malignant (plasmacytoma) mouse tissues and for DNA from liver, sperm and developing embryos of the loach. It has been shown that the measuring of DNA renaturation kinetics makes it possible to reveal differences in the content of certain fractions of the repetitions in the genomes of different species. Moreover, differences in the distribution of the repetitions between hetero- and euchromatine can be identified. Loach embryo DNA (blastula stage) was shown to contain larger amount of the fraction renaturing at Cot less than 10(-2) as compared to liver and sperm DNAs (by 5%). An enrichment with respect to the intermediate repetitions (10(-2) less than Cot less than 10(2)) was found in the mouse plasmacytoma DNA as compared to the spleen DNA. The nature of these distinctions is discussed.

Animals↗