No abstract

The activity of alanine-α-ketoglutarate transaminase in rat liver was found to be uniform during the first 6 weeks of life, increasing thereafter until at 48 weeks of age the specific activity was seven times greater than in the immature rat. In rats varying in age from 4 days to 24 weeks, treatment with 1 mg of cortisol for 4 days resulted in significant increases in hepatic alanine transaminase activity. Female rats were less responsive to cortisol treatment than were males. Fetal rat liver had significantly lower alanine transaminase activity than did newborn animals and the activity of this enzyme in fetal liver was not altered by cortisol treatment. Adrenalectomy of adult male rats, but not immature male rats, resulted in a decrease in alanine transaminase activity; after 48 hr, enzyme activity was depressed to levels found in unoperated immature rats. The sensitivity of the adrenalectomized animals to cortisol administration was comparable to that of intact animals. In contrast, the aspartate-α-ketoglutarate transaminase was not appreciably altered following cortisol treatment or adrenalectomy and did not increase with age.

In rats treated with furosemide, urinary losses of water, sodium and potassium were accompanied by increased circulating levels of aldosterone. Trilostane, an inhibitor of adrenal 3/3-hydroxysteroid dehydrogenase activity, prevented furosemide-induced hyperaldosteronism which resulted in a partial inhibition of diuretic-induced kaliuresis without a change in sodium and water excretion. Spironolactone, an antagonist of mineralocorticoid action with inherent diuretic activity, produced qualitatively similar effects to those of trilostane on urinary electrolyte excretion in furosemide-treated intact rats. However, mineralocorticoid-induced potassium loss in adrenalectomized rats was not altered by trilostane but was prevented by spironolactone reflecting the direct effect of spironolactone on the kidney. In addition, furosemide-induced kaliuresis in adrenalectomized rats was not prevented by trilostane. Therefore, although both trilostane and spironolactone reduce diuretic-induced potassium loss, spironolactone acts by competing with aldosterone for the mineralocorticoid receptor while trilostane appears to act exclusively by preventing secondary hyperaldosteronism. o 1984 Society for Experimental Biology and Medicine. 388

(exo, exo)-2-Aryltropane-3-carboxylic esters of types 6, 7, and 10 lower circulating blood glucose levels by 60--80%. This activity is accompanied by an analgesic activity roughly equal to that of codeine. Both of these activities reside in the 1R enantiomer and extensive structure-activity studies failed to separate them. The specific opioid antagonist nalorphine blocks the analgesic activity but does not diminish the hypoglycemic action. Conformational integrity afforded by the ethylene bridge is neccessary for the observed activities.

Alanine transaminase activity is increased markedly in the liver of rats treated with glucocorticoids or corticotropin( 1-3). In contrast, treat men t with deoxycor ticm terone (2 ) or adrenalectomy (4) caused a significant reduction in level of this transaminase in liver. The stimulatory action of cortisol on hepatic alanine transaminase activity was not impaired when this steroid was given in combination with deoxycorticosterone( 2 ) . The purpose of this study was to determine whether the fall in liver alanine transaminase f 0110 wing administration of deoxycor t icos t erone is related to its inhibitory effect on release o:f corticotropin by the pituitary.Materials and methods. Male hypophysectomized rats of the Sprague Dawley strain, obtained from the Charles River Laboratories were used. Rats were adrenalectomized 5 days prior to use and were given either 11-deoxycorticosterone or one per cent saline in place of drinking water. Deoxycorticosterone was administered subcutaneously as an aqueous suspension. Corticotropin (10 I.U. per injection, 20 I.U., total dose) ( ACTHAR GEL, Armour Pharmaceutical Co.) was administered twice daily. Purina Laboratory Diet was fed ad libitum to all animals.The animals were stunned by a blow on the head, then killed by exsanguination. The livers were immediately placed in beakers on crushed ice. Homogenates were prepared in a Waring Blendor with ice-cold distilled water. Alanine-and aspartate-a-ketoglutarate transaminase activities were measured by procedures ( 2 ) similar to those described by Wroblewski and La Due(5) except that instead of measuring the oxidation of DPNH spectrophotometrically, DPN was determined *Paper No. 5 in the series on Corticosteroids and Transaminase Activity. This work was supported in part by a research grant from Nat. Inst. of Arthritis and Metab. Dis. by a fluorometric procedure developed by Lowry and co-workers ( 6 ) . Tyrosine-a-ketoglutarate transaminase activity was determined using a modification of the method described by Sereni and co-workers(7). Protein was determined by a modification of the Folin procedure( 8).The data presented in Table I indicate that treatment of rats with dmxycorticosterone (DOC) causes a marked reduction in liver alanine transaminase activity. Administration of DOC to adult rats depressed the activity af this transaminase to 42% of control value. Treatment of younger animals with DOC also lowered the values of this transaminase in liver to 30% af normal.The depression in hepatic alanine transaminase activity which followed adrenalectomy was comparable to that observed in unoperated rats treated with dmxycorticosterone ( Table I). In contrast to the effect of DOC on alanine transaminase activity in intact animals, treatment of adrenalectomized rats with DOC for 14 days did not further reduce the activity of this enzyme in liver.On the basis of these results, a direct effect of DOC on alanine transaminase appeared unlikely. The possibility that DOC might act by impairing the secretion of corticotropin by the hypophys...