Effects of adrenalectomy and spironolactone on urinary metabolites of aldosterone in rats

The quantities and temporal sequences of appearance of aldosterone metabolites in the urine of adrenalectomized rats, and adrenalectomized rats treated with spironolactone, were compared following subcutaneous administration of a physiological dosage (0.05 microgram) of [1,2,-3H]aldosterone. Large amounts of radiometabolites were rapidly excreted during 0-1 and 1-3 h and only small quantities by 3-4 h in urine of both groups of rats. The majority of the urinary radiometabolites (70-85%) were identified by Sephadex DEAP-LH-20 chromatography as neutral metabolites of aldosterone (NMA), together with lesser quantities of acidic, sulfate, and glucuronide conjugates. Further characterization by high pressure liquid chromatography (HPLC) showed that 90% of the NMA excreted by adrenalectomized rats were polar metabolites which could be separated into at least 15 peaks eluting in regions of increasing polarity (designated A, B, C, and D). Only small quantities of unaltered [3H]aldosterone and no ring-A-reduced metabolites were excreted by the adrenalectomized rats. Spironolactone treatment caused large changes in the excretion of acidic and sulfate derivatives of aldosterone, as well as discrete alterations in the HPLC patterns of the polar NMA (particularly those metabolites in regions A and B). Such discrete changes in these metabolic pathways which occur at the same time as the hormonal actions of aldosterone in the kidney may provide further insight into understanding the biological role of aldosterone metabolism.     

Effect of dietary protein on the capacity of urea synthesis in rats

The in vivo capacity of urea nitrogen synthesis (CUNS) during alanine stimulation was measured within the blood amino acid concentration interval 7.3-11.6 mmol/l, where urea synthesis is at maximum and independent of substrate concentration. Three groups of rats were fed for 14 days, either a low protein diet (8%), a normal diet (17%), or a high protein diet (53%). Diet protein modified both CUNS and plasma glucagon concentration. CUNS was 5.86 +/- 2.93, 7.43 +/- 2.16, and 19.31 +/- 4.32 mumol/(min.100 g BW) (mean +/- SD, N = 6), respectively. The corresponding plasma glucagon concentrations after alanine stimulation were 222 +/- 400, 633 +/- 229, and 1700 +/- 627 ng/l, respectively. The in vivo kinetics of urea production is regulated by dietary protein, possibly via glucagon. This implies that the liver plays an active part in adaptation of whole body nitrogen homeostasis to dietary changes.     

Effects of adrenalectomy and hydrocortisone on DNA synthesis in the rat anterior pituitary gland

The effect of adrenalectomy and hydrocortisone on /³H/-thymidine uptake by rat anterior pituitary cells in the short-time organ culture was investigated. Adrenalectomy significantly increases the incorporation tritiated thymidine into anterior pituitary cells nuclei, whereas hydrocortisone has an opposit effect. The existence on negative feedback between the intracellular hormone content and DNA synthesis in ACTH-secreting anterior pituitary cells is suggested.