Hypox Animals Research Articles

Growth-hormone dependence of non-suppressible insulin-like activity (NSILA) and of NSILA-carrier protein in rats.

ABSTRACT The effects of hypophysectomy and subsequent growth hormone (GH) treatment on the serum levels of NSILA and of its binding protein were studied in rats. After hypophysectomy NSILA levels fall to 6 % of the normal. Under GH treatment they rise slowly to 65 % of normal after 12 d. In parallel with the changes of serum NSILA, [35S] sulphate incorporation into costal cartilage in vitro is markedly decreased in hypox animals and restored towards the normal by GH treatment. The relative binding activity of [125I] NSILA-S of serum "stripped" from endogenous NSILA is also reduced after hypophysectomy to approx. 30 % of normal, i. e. to a lesser extent than serum NSILA levels. This concentration of binding protein is sufficient to bind trace amounts of labelled NSILA-S. The half-life of an intravenously injected tracer of [125I]NSILA-S is not significantly decreased in hypox animals. Substitution with GH results in a rise of the relative binding activity to normal after 12 d. Chromatography of serum, equilibrated with [125I]NSILA-S tracer, on Sephadex G-200 at neutral pH reveals different radiochromatographic patterns for serum from hypox and normal rats: In hypox rats the main peak of radioactivity appears at 60 % bed volume, in normal rats between 45 and 50 %. During GH treatment this main peak shifts from 60 back to 45–50 %. The distribution of binding activity is similar for normal and hypox rat serum after chromatography on Sephadex G-200 at acidic pH. Furthermore, the binding characteristics of "stripped" hypox and normal serum are identical. This suggests that the same binding protein is present in the normal and hypox rat serum in different molecular forms. It is concluded that GH is a major factor regulating the level of NSILA and of its binding protein in the rat.

Effect of hypophysectomy on p-aminohippurate transport kinetics in rat renal cortical slices.

Recent work on kidneys from hypophysectomized (hypox) rats has shown atrophy of the proximal tubules with no effects on the other parts of the nephron. We carried out experiments to determine whether the reduction of p-aminohippurate (PAH) is consistent with structural changes in the proximal tubule of hypophysectomized rats. Initial velocities of PAH uptake by renal cortical slices were found to be constant over 30 min of incubation at concentrations of PAH up to 0-5 mmol/1 for both control and hypox animals. Using kinetic analysis, it was found that both maximal velocity, Vmax, and the Michaelis constant, Km, were reduced in hypox animals, the relative reduction being similar for both parameters. Comparison between high Na (100 mmol/1) and low Na (6 mmol/1) media indicated that in both control and hypox rats, Vmax was significantly lower in low Na medium than in high Na medium, whereas Km was not changed. Efflux of PAH from pre-loaded tissue also showed a reduction in hypox animals. These results may indicate that hypophysectomy alters the capacity of PAH transport in renal cortical slices by (1) reducing the effective transport area or sites, and (2) by changing carrier-substrate affinity.

Effect of Hypophysectomy on the Metabolism of Essential Fatty Acids in Rat Testes and Liver

The effect of hypophysectomy on lipid classes and interconversion of linoleic acid in livers and testes of essential fatty acid (EFA)-deficient rats is described. Male rats of the Sprague Dawley strain made EFA-deficient by feeding them a fat-free diet from weaning to 26 weeks of age were used. Hypophysectomy caused a marked elevation of the percentage of cholesteryl esters, glyceryl ether diesters and triglycerides at the expense mainly of phosphatidylcholine and phosphatidylethanolamine in the testes. There was a small effect of hypophysectomy on the composition of the liver lipids with only a slight increase in the percentage of polar lipids and corresponding slight decrease in the percentage of the neutral lipid fraction 3 weeks after the operation. The characteristic pattern of fatty acid interconversions, on feeding linoleate, occurred in both livers and testes of hypophysectomized (hypox) animals. However, the conversion of linoleic acid to higher polyunsaturated fatty acids was not as efficient in the testes of hypox as normal animals. Despite the marked change in fatty acid composition produced from feeding linoleate there appeared to be little effect on the pattern of changes in lipid class composition caused by hypophysectomy. The results suggest that the hypophyseal hormones exercise control over the transformation of fatty acids among the lipid classes.

Mineralocorticoid hypertensive cardiovascular disease induced in hypophysectomized rats.

Reports in the literature to the contrary, hypertensive cardiovascular disease proved to be readily induced by desoxycorticosterone in hypophysectomized rats sensitized to steroid action by partial nephreetomy and high NaCl intake. In the absence of the pituitary, however, hypertension was somewhat slower in onset and progress. Although hypophysectomized animals were able to develop hypertension as severely as did intact animals, they were not, as judged by their better survival and less evident cardiorenal vascular lesions, as severely injured thereby. Contrasted with their exuberant development in hypertensive intact animals, renal lesions in hypertensive hypophysectomized animals were rare. Necrotizing arteritis in the heart was seen in about half of the hypox animals, and periarteritis nodosa of pancreatic and mesenteric arteries was more widespread and severe than in similarly treated intact animals which had, however, died earlier. Steroid treated animals bearing pituitary autotransplants beneath the renal capsule, developed more severe and widespread cardio-renal lesions than did similarly treated hypophysectomized animals, but incidence and severity of periarteritis nodosa in splanchnic arteries was about the same in each. The ingestion of sodium chloride caused "salt hypertension" in some of the pituitary-bearing controls, but not in either hypophysectomized or autotransplant-bearing controls.