Long-term Glucocorticoid Administration Research Articles

Influence of growth hormone on the immunosuppressive effect of prednisolone in mice

Growth hormone can be used to counteract some catabolic effects of long-term administration of glucocorticoids, such as impairment of growth in children and osteoporosis. However, owing to its immunostimulatory properties the hormone may counteract the effect of glucocorticoids on the immune system. To investigate this question we administered different doses of hGH (4, 8, 40 IU/kg) to C57/Bl/6J mice treated for two days with prednisolone, and evaluated thymus and spleen parameters and natural killer activity. Growth hormone at the dose of 4 and 8 IU/kg reversed prednisolone-induced reduction of spleen and thymus weight and cellularity, whereas the highest dose showed to be immunosuppressive in itself. Two days after treatment withdrawal, a recovery of spleen parameters was evident, whereas the thymus was still suppressed by preceding prednisolone or hGH (40 IU/kg) treatments. The pattern of natural killer activity displayed by the splenocytes resembled that present under treatment. In a second experiment prednisolone, administered for 10 days, drastically reduced the number of viable spleen and thymus cells as well as the relative spleen and thymus weights, an effect reversed by concomitant administration of hGH (0.8, 4, 8 IU/kg). Natural killer activity, which was significantly depressed by prednisolone, was restored by the intermediate GH dose only. The 8 IU/kg GH dose was immunosuppressive in itself.

Effects of melatonin on genetic hypercholesterolemia in rats

Administration of the pineal hormone melatonin to genetically hypercholesterolemic rats resulted in a decrease in plasma cholesterol levels and in an improvement of fatty changes of the liver. Thus, the antihyperlipemic effect of melatonin, which was first discovered in hypercholesterolemia produced by short- or long-term administration of glucocorticoids, has now been proved to be rather universal and not simply anti-glucocorticoidal. The mechanism of the decrease of plasma cholesterol levels remains unknown. It was also found that the pathogenesis of this so-called genetic hypercholesterolemia in rats involved biochemical nephrotic changes and histopathological changes in the kidney.

Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat.

Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats.

Nonenzymatic addition of glucocorticoids to lens proteins in steroid-induced cataracts.

A frequent manifestation of long-term glucocorticoid administration is the occurrence of posterior subcapsular cataracts. The molecular basis for this effect has not yet been elucidated. The addition of prednisolone to the rat lens in culture results in a time- and concentration-dependent lens opacification that correlates with the formation of covalent prednisolone-lens protein adducts. Prednisolone adduct formation was analyzed by [3H]prednisolone incorporation and by immunoprecipitation with antiserum specific for proteins modified by the nonenzymatic addition of prednisolone. In the rat lens, these adducts were localized in both the water-soluble and urea-soluble lens protein fractions. Gel electrophoresis and fluorography revealed that the most extensively modified proteins were two crystallins subunits. Lens proteins from 33 normal and cataractous human lenses were fractionated and analyzed for the presence of prednisolone-protein adducts by competitive radioimmunoassay. Adducts were detected only in those samples derived from glucocorticoid-induced cataractous lenses. We conclude that elevated glucocorticoid levels lead to the formation of glucocorticoid-lens protein adducts both in vitro and in vivo. Lens protein modification by glucocorticoids may lead to sufficient biochemical or structural alterations so as to result in cataract formation. The ability of glucocorticoids to form adducts with proteins in vivo also may play a role in some of the other toxic manifestations of long-term glucocorticoid therapy.

Clinical studies on TRF test. 4. TRF test in Cushing's syndrome and long-term glucocorticoid administration

TRFによるTSH放出に及ぼすglucocorticoid (G) の影響を観察した.この結果, Gの大量, 長期, 連続投与症例では一定量のTRFによるTSH放出が抑制されており, 一方少量, 短期, 間歇投与症例ではTRF効果は修飾を受けなかつた.副腎皮質腺腫によるCushing症候群においても一定量のTRFによるTSH放出が抑制されていた.TRF投与量を増すとG投与例においても正常とほぼ等しいTSH増量反応が認められた.

PSYCHOSOMATIC SIGNIFICANCE OF A CONCAVE RS-T ELEVATION IN CHEMICALLY NORMAL HEARTS.

An ST elevation in the left precordial leads is one of our five criteria for the pattern of actual peurosis (Boss). Further analytic and psychotherapeutic approaches were made to those patients with normal hearts which show a concave RS-T elevation in the left precordial leads. Examples of the life history of patients with a concave RS-T elevation were described. The development of a concave RS-T elevation by stress and its normalization by psychotherapy were demonstrated. The concave RS-T elevation similar to that found in patients with actual neurosis was found in patients treated by a long-term administration of glucocorticoids.