Hepatic Tyrosine Aminotransferase Activity Research Articles

Effects of sulcotrione [2-(2-chloro-4-mesylbenzoyl)-cyclohexane-1,3-dione] on enzymes involved in tyrosine catabolism and the extent of the resulting tyrosinemia and its relationship with corneal lesions in rats

We aimed to investigate the effects of subchronic exposure to sulcotrione on the enzymes involved in tyrosine catabolism and the extent of the resulting tyrosinemia and corneal lesions in rats. Daily oral administration of sulcotrione at 0.1, 0.5, 5, 50 and 100 mg/kg/day markedly inhibited hepatic 4-hydroxyphenylpyruvate dioxygenase (HPPD). In response to the tyrosinemia, the activity of hepatic tyrosine aminotransferase (TAT) at each dose level was insignificantly induced and hepatic homogentisic acid oxidase (HGO) at 5, 50 and 100 mg/kg/day was markedly reduced. Repeated oral administration of sulcotrione to rats at doses of 5, 50, and 100 mg/kg/day for 90 days produced corneal lesions with an incidence of 18.8%, 75.0% and 56.3%, respectively. The significant increase in tyrosine levels indicates that the occurrence of corneal lesions in rats exposed to sulcotrione was not only associated with the concentration of tyrosine in the ocular fluid, but also with other, unidentified factors.

Serine dehydratase and tyrosine aminotransferase activities increased by long‐term starvation and recovery by refeeding in rainbow trout (Oncorhynchus mykiss)

Here, we study a cycle of long-term starvation followed by refeeding in relation to the kinetics of serine dehydratase (SerDH) and tyrosine aminotransferase (TyrAT) in rainbow trout (Oncorhynchus mykiss). We determine SerDH- and TyrAT- specific activity at different substrate concentrations in liver and white muscle of juvenile trout starved for 70 days and then refed for 6 hr, 32 hr, 4 days, and 9 days. SerDH showed a hyperbolic kinetic with a K(m) for L-serine of 77.07+/-8.78 mM in the liver of control trout. After 70 days of starvation, the SerDH activity at saturate substrate concentration rose 100% over control. No significant changes were found in the K(m) values of the enzyme. After refeeding, the SerDH activity declined to control values. TyrAT also showed a hyperbolic kinetic with a K(m) for L-tyrosine of 1.86+/-0.12 and 2.55+/-0.57 mM in liver and white muscle, respectively. In starved trout, TyrAT activity in liver and white muscle was about 64 and 267%, respectively, higher than control. After 9 days of refeeding, the control values recovered, although, at 6 hr of refeeding, hepatic TyrAT activity was higher than that for starvation. This work shows that SerDH and TyrAT are present in rainbow trout and that the two enzymes have regulatory functions in the catabolism of their respective amino acids in this species.

Hepatotoxin-induced hypertyrosinemia and its toxicological significance

A (1)H Nuclear Magnetic Resonance (NMR) spectroscopic investigation of the effects of single doses of four model hepatotoxins on male Sprague-Dawley rats showed that hypertyrosinemia was induced by three of the treatments (ethionine 300 mg/kg, galactosamine hydrochloride 800 mg/kg and isoniazid 400 mg/kg) but not by the fourth (thioacetamide 200 mg/kg). Concomitant histopathological and clinical chemistry analyses showed that hypertyrosinemia could occur with or without substantial hepatic damage and that substantial hepatic damage could occur without hypertyrosinemia. However, in the rats dosed with galactosamine hydrochloride, which showed highly variable amounts of liver damage at ca. 24 h after dosing, a clear relationship was found between the degree of hypertyrosinemia and the extent of the hepatic necrosis induced. In line with the cause of clinically observed Type II Tyrosinemia, we consider that the critical event in the onset of hepatotoxin-induced hypertyrosinemia is likely to be a reduction in hepatic tyrosine aminotransferase (TAT) activity. We discuss mechanisms by which TAT activity could be lost with special consideration given to pyridoxal 5'-phosphate (P5P) depletion and to the inhibition of protein synthesis. This analysis may have implications for the interpretation of clinical measures of liver status such as Fischer's ratio and the branched-chain tyrosine ratio (BTR).

Hepatic tyrosine aminotransferase activity is affected by chronic heat stress and dietary tyrosine in broiler chickens

1. Two experiments were conducted to investigate the impact of high temperature and dietary tyrosine (Tyr) content on performance and activity of hepatic tyrosine aminotransferase (EC 2.6.1.5.), an enzyme that catalyses the first step in the metabolic degradation of Tyr in broiler chickens. 2. Two-week-old birds were allocated to one of three temperature treatments: 24 ° C (control), 36 ° C (heat stress, HS) and 24 ° C pair-fed (24PF) for 2 weeks and fed on diets containing 100% (Experiment 1) and 50, 100 and 200% (Experiment 2) of the NRC requirement for Tyr. 3. In Experiment 1, exposure of chickens to 36 ° C for 2 weeks caused significant increase in hepatic tyrosine aminotransferase activity but no significant change in activity of hepatic phenylalanine 4-hydroxylase (EC 1.14.16.1) (an enzyme that catalyses conversion of phenylalanine to Tyr) compared with the 24PF birds. No significant changes attributable to heat stress were detected in hepatic glutamic-oxaloacetic transaminase (EC 2.6.1.1) activity. 4. In Experiment 2, heat stress caused reductions in weight gain and feed intake in chickens on all diets, compared with their control counterparts. Hepatic tyrosine aminotransferase activity was increased by heat stress compared with their 24PF counterparts in chickens fed on the 100 and 200% Tyr diets, while in chickens fed the 50% Tyr diet, it was reduced by heat stress. 5. From these results, it is suggested that hepatic tyrosine aminotransferase activity is affected by heat stress and dietary Tyr content and the increased tyrosine aminotransferase activity with, in part, relatively low phenylalanine hydroxylase activity in hepatic tissues may be involved in the Tyr metabolism characteristic of heat-stressed chickens.

Tissue distribution of 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) and its effect on enzymes involved in tyrosine catabolism in the mouse

Administration of a single oral dose of 2-(2-nitro-4-trifluoromethyl-benzoyl)-cyclohexane-1,3-dione (NTBC) to mice increases the concentration of tyrosine in the plasma and aqueous humour. The tyrosinaemia is both time and dose-dependent with a single dose of 30 μmol NTBC/kg (10 mg/kg) producing maximal concentrations of tyrosine in plasma of about 1200 nmol/ml and in aqueous humour of about 2200 nmol/ml at 16 h after dosing. Analysis of the key hepatic enzymes involved in tyrosine catabolism, following a single dose of 30 μmol NTBC/kg, showed that 4-hydroxyphenylpyruvate dioxygenase (HPPD) was markedly inhibited soon after dosing and that the activity recovered very slowly. In response to the tyrosinaemia, the activity of hepatic tyrosine aminotransferase (TAT) was induced about two-fold, while the activity of hepatic homogentisic acid oxidase (HGO) was reduced at 4 and 5 days after dosing. Daily oral administration of NTBC at doses up to 480μmol NTBC/kg (160mg/kg/day) to mice produced a maximal tyrosinaemia of about 600-700nmol/ml plasma, showing some adaptation relative to a single dose. Unlike the rat, no treatment-related corneal lesions of the eye were seen at any dose levels up to 6 weeks. Administration of a single oral dose of [ 14C]-NTBC at 30μmol/kg led to selective retention of radiolabel in the liver and to a lesser extent the kidneys. Our studies show that NTBC is a potent inhibitor of mouse liver HPPD, which following repeat exposure produces a marked and persistent tyrosinaemia, which does not result in ocular toxicity.

Vitamin B-6 Deficiency and Level of Dietary Protein Affect Hepatic Tyrosine Aminotransferase Activity in Cats

Total activity [pyridoxal 5′-phosphate (PLP) added in the assay] of hepatic tyrosine aminotransferase (TAT) measured in cats at 0300, 0900, 1500 and 2100h was 10.3 ±1.1, 14.0 ± 0.7, 9.8 ± 1.3 and 11.0 ± 0.7 nkat/g liver, indicating little diurnal variation. Activity after 18 h of food deprivation was 10.0 ± 0.3 nkat/g liver, also not different from cats that were eating ad libitum. These findings support the idea that cats have only limited changes in the activity of hepatic TAT compared with rats. Total TAT activity was measured in cats fed high protein (550 g/kg) and low protein (180 g/kg) diets for 4 wk. Cats fed a high protein diet had activities significantly higher (about twice) than cats fed the low protein diet. Hepatic TAT activity of vitamin B-6-deficient cats (diet without pyridoxine for 9 wk) was compared with cats given the same diet with 8 mg pyridoxine/kg. Total hepatic TAT activity in deficient cats was significantly (P < 0.05) lower per gram soluble or total protein (but not per gram liver) than control cats; holoenzyme activity and percentage of active enzyme in deficient cats were also significantly lower by 75 and 64%, respectively. The apparent Km of TAT from cats for tyrosine (2.1 mmol/L) was similar to that for rats (1.9 mmol/L), but higher for PLP in cats (0.16 μmol/L) than rats (0.034 μmol/L). Part of the reason for the higher plasma tyrosine in vitamin B-6–deficient cats than rats is the higher Km of TAT for PLP in cats than rats.

The Effect of a Low-Protein Diet and Dietary Supplementation of Threonine on Tyrosine and 2-(2-Nitro-4-trifluoromethylbenzoyl) cyclohexane-1,3-dione-Induced Corneal Lesions, the Extent of Tyrosinemia, and the Activity of Enzymes Involved in Tyrosine Catabolism in the Rat

Rats fed a low-protein diet and administered 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC) orally at 30 μmol/kg/day (10 mg/kg/day) or fed a low-protein diet containing 5 ppm NTBC develop lesions to the cornea of the eye within 3–8 days of exposure with an incidence of about 80%. This treatment also produces a marked inhibition of both hepatic and renal 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, an induction of hepatic but not renal tyrosine aminotransferase activity, and a marked tyrosinemia in the plasma and aqueous humor. The extent of tyrosinemia and changes in the activity of tyrosine catabolic enzymes are similar to those reported for rats fed a normal protein diet and administered NTBC orally at 30 μmol/kg/day. However, the onset of corneal lesions occurs much earlier in rats fed a low-protein diet. The adverse ocular effects of NTBC can be alleviated by supplementing the low-protein diet with 1% w/w threonine. The protection afforded by threonine inclusion in the diet was not due to any amelioration in the extent of inhibition of hepatic HPPD activity or reduction in the extent of the tyrosinemia as measured 8 days after treatment. Rats fedl-tyrosine at 5% w/w in a low-protein diet rapidly develop lesions to the cornea of the eye, which are associated with a marked tyrosinemia, increased hepatic tyrosine aminotransferase activity, and about a 50% reduction in the activity of hepatic HPPD. The onset of corneal lesions produced by feeding a high tyrosine diet could be delayed, but not prevented, by inclusion of 1% w/w threonine in the low-protein diet. The basis for the beneficial effect of dietary supplementation of threonine in alleviating the corneal lesions produced by NTBC is unclear. However, our findings do illustrate that protein deficiency limits the ability of the rat to respond to a tyrosine load produced by inhibition of HPPD.

Effects of Indomethacin on the Pharmacokinetics and Pharmacodynamics of Prednisolone in Rats

The effect of indomethacin on the disposition of prednisolone and the induction of tyrosine aminotransferase (TAT) was examined in male Sprague‐Dawley rats. Rats were pretreated with either indomethacin (5 mg/kg, intraperitoneally) or phosphate buffered saline (control) twice daily for 6 days followed by a single dose of prednisolone. Blood samples were collected after prednisolone administration. In separate animals, hepatic TAT activity (pharmacologic effect) was measured 4 h after the prednisolone dose. In addition, the effect of indomethacin on thein vitroprotein binding of prednisolone was examined in pooled rat and human plasma. The clearance and apparent volume of distribution of prednisolone in the control and indomethacin‐treated animals were similar, averaging 4.71 versus 4.05 L/h/kg and 1.37 versus 1.33 L/kg, respectively. The elimination half‐life was 0.48 h in both groups. Indomethacin also did not affect the protein binding of prednisolone in rat or human plasma. However, indomethacin pretreatment increased the hepatic TAT activity induced by prednisolone. These studies indicate that indomethacin may affect the pharmacological effects of prednisolone without influencing its pharmacokinetics.

Effects of Glucocorticosteroids and Insulin on Tyrosine Aminotransferase Activity in Isolated Chick Embryo Hepatocytes and in Intact Embryos in Ovo

Hepatocytes were isolated from 17-day-old chick embryos. Steroid hormones or insulin, alone or when combined, did not alter tyrosine aminotransferase (TAT) activity in the isolated hepatocytes. However, TAT was stimulated by glucocorticoids in mixed hepatocyte and fibroblast cocultures; hormonal effects were not observed in pure hepatocyte cultures. Administration of hydrocortisone, dexamethasone, or triamcinolone (singly) to chick embryos in ovo resulted in an increase in hepatic TAT activity; insulin injection was without effect on the enzyme. The stimulation of TAT activity evoked by glucocorticosteroids in ovo was abolished by injection of cycloheximide or cordycepin. These observations contrast with reported glucocorticosteroid actions on TAT activity in fetal rat liver. It would appear that the differential regulatory effects on hepatic TAT by glucocorticosteroids are imposed by the distinct nutrient environments of chick embryos and fetal rats.

Dehydroepiandrosterone regulation of the hepatic glucocorticoid receptor in the zucker rat. The obesity research program

Dehydroepiandrosterone (DHEA) decreases the activity of hepatic tyrosine aminotransferase (TAT), a glucocorticoid-inducible enzyme, in the obese, hypercorticosteronemic Zucker rat. To investigate the mechanism of this antiglucocorticoid action, the effect of exogenous DHEA on hepatic glucocorticoid receptor (GC) number and affinity was quantitated. Food supplementation with DHEA (0.6% w/w) for 1 or 7 days had no effect on either receptor number or affinity in obese Zucker rats. After 28 days, however, DHEA treatment resulted in a nearly 40% decrease in cytosolic hepatic receptor content (B max; fmol/mg cytosolic protein) without any change in affinity ( K d ) in both lean and obese rats. DHEA treatment for 28 days also resulted in an increased liver size and cytosolic protein content. When the hepatic GC receptor content was normalized based on the change in liver size and protein content, the apparent number of GC binding sites per liver was not affected by DHEA treatment. This observation suggests that DHEA's effect on GC receptor content may not be a specific action and that downregulation of the GC receptor is not the mechanism of DHEA action on GC induced TAT activity. This is supported by the effect of DHEA on obese rat TAT activity in the same experiment where the greatest inhibition occurred after only 1 day of treatment. From these experiments it is concluded that although long-term DHEA treatment may decrease the relative concentration of GC receptors in rat liver, this change is not the mechanism through which DHEA mediates its acute antiglucocorticoid action.

A possible mechanism for the increase in brain tyrosine levels induced by cyanide in mice

Subcutaneous administration of cyanide significantly increased blood tyrosine levels of mice in a dose dependent manner. Tyrosine aminotransferase activity in liver of mice was significantly decreased in the presence of cyanide (8, 10, 20, 40, 50, 65, 80 and 100 μ M), also in a concentration-dependent manner, with a positive correlation between the percentage increase of blood tyrosine levels and the percentage decrease of hepatic tyrosine aminotransferase activity. These results suggest that the increased tyrosine levels induced in blood by cyanide may be related to its inhibition of tyrosine aminotransferase activity in the liver. Cyanide decreased hepatic ATP content and increased blood ammonia levels and brain tyrosine in a dose-dependent manner. As it is known that hyperammonaemia increases the uptake of neutral amino acids such as tyrosine into the brain from blood, the mechanism by which tyrosine levels increase in the brain may be based on increases of both tyrosine and ammonia levels in blood.

Stress-induced changes of glucocorticoid receptor in rat liver

The effect of corticosterone injection and of acute and repeated stress on rat liver cytosol glucocorticoid receptor was studied to ascertain whether corticosterone-induced glucocorticoid receptor (GR) regulation also takes place in intact animals as it does in adrenalectomized ones. Adult male rats were exposed to six different stressors (swimming, 10 mg/kg histamine i.p., 500 mU/kg vasopressin s.c., heat, immobilization and cold) acutely or three times daily for 18 days (repeated stress). Each of the stressors applied acutely provoked a pronounced increase of plasma corticosterone with subsequent induction of hepatic tyrosine aminotransferase activity. Depletion of cytosol receptor was however only noticed after swimming and histamine injection. On the other hand, sustained hypersecretion of corticosterone evoked by repeated stress significantly reduced the number of GR in rat liver cytosol without any change in K d . It is concluded that in the presence of intact adrenal glands cytosol receptors are more resistant to corticosterone-induced depletion than in their absence. Further, repeated stress causes down-regulation of GR in the liver, most probably by sustained corticosterone secretion, yet the effect of other stress factors cannot be excluded.

Dehydroepiandrosterone: Antiglucocorticoid Action in Mice

The acute effect of dehydroepiandrosterone (DHEA) and its conjugate, DHEA-sulfate (DHEA-S) on glucocorticoid action was tested in vivo using male Swiss-Webster mice. The authors found that DHEA and DHEA-S significantly inhibited induction of hepatic tyrosine aminotransferase activity, although the former was more potent. This inhibition was dose- and time-dependent and was not demonstrable with other steroids. The same inhibitory effect of DHEA was seen with kidney tyrosine aminotransferase induction, as well as with liver and kidney ornithine decarboxylase enzyme activity, another glucocorticoid-induced enzyme. The conclusion is that DHEA acts acutely as an antiglucocorticoid and exerts its effect in different glucocorticoid-sensitive systems.

The effect of exercise, diet restriction, and aging on the pituitary - adrenal axis in the rat

The effects of calorie restriction, exercise, and aging on the pituitary-adrenal axis were studied in male Wistar rats from 12 to 28 months of age. There were 4 experimental groups: sedentary, ad libitum fed (A); sedentary, diet restricted by feeding on alternate days (R); exercised by swimming on alternate days, ad libitum fed (AE); exercised as AE, diet restricted as R (RE). Pituitary-adrenal function was assessed by measuring serum ACTH and corticosterone concentrations, adrenal weight, hepatic glucocorticoid receptor concentration, and hepatic tyrosine aminotransferase (TAT) activity. Serum corticosterone concentration increased with age while serum ACTH decreased from 12 to 20 months of age and then increased thereafter. TAT activity decreased and receptor concentration remained constant with age. Adrenal weights increased with age; those of AE rats increased dramatically. Analyses for relationships between variables revealed a quadratic relationship between serum ACTH and corticosterone concentrations. There tended to be an inverse relationship between TAT activity and corticosterone concentration. These observations may be indicative of a loss of feedback loop integrity with aging. Neither calorie restriction nor exercise were able to maintain the integrity of pituitary-adrenal function during aging, though dietary restriction did slow age-associated decrements of TAT activity.

Second generation model for prednisolone pharmacodynamics in the rat

An improved model describing receptor/gene-mediated pharmacodynamics of prednisolone is presented which consists of seven differential equations. Data for plasma prednisolone concentrations, free hepatic glucocorticoid receptors, and hepatic tyrosine aminotransferase activity (TAT) following low (5 mg/kg) and high (50 mg/kg) doses of prednisolone are used to quantitate the kinetics and dynamics of this synthetic steroid in the rat. In contrast to the earlier model, the newer model provides for a coupling and simultaneous fitting of receptor and TAT data and is able to describe the recycling of receptors between cytosol and nucleus and the return of cytosolic receptors to baseline following glucocorticoid elimination. A numerical technique to determine the efficiency of TAT induction based on area under the curve calculations is presented, which supports the hypothesis that nonlinear dose-response effects are due to dose and time-dependent receptor depletion in the cytosol. Simulations are presented to examine the major determinants of corticosteroid effects and to compare the effects of single- and multiple-dose regimens in maximizing drug effects.

The increase in hepatic tyrosine aminotransferase activity by ethanol administration involves an acceleration of enzyme synthesis

The present study was conducted to examine the nature of the increase in tyrosine aminotransferase (TAT) activity by acute ethanol administration. A significant rise in aminotransferase activity was observed as early as 1 hr after intact rats were gavaged with ethanol. Ethanol administration also increased TAT activity in adrenalectomized rats. Inhibition of ethanol metabolism by pyrazole administration had no effect on the ethanol-induced increase in TAT activity. Immunochemical analyses revealed that the enhancement of TAT activity in ethanol-fed rats correlated with an increase in aminotransferase protein. Measurement of the rate of TAT synthesis showed that in ethanol-fed rats, [3H]leucine was incorporated into the aminotransferase protein at a higher rate than in controls by a factor which was similar to the enhancement in enzyme activity. Our findings indicate that an acceleration of TAT synthesis fully accounts for the increase in TAT activity during the early stage of enzyme induction. TAT induction by ethanol administration is not dependent upon an increase in adrenal corticosteroid production, nor does it require ethanol metabolism.

Alterations in the hepatic glucocorticoid response to mirex treatment

Corticosterone has been shown to be involved in the regulation of mirex-induced adaptive liver growth. To further investigate the role of corticosterone in this response, plasma corticosterone, hepatic tyrosine aminotransferase (TAT) activity, and hepatic cytosolic binding of glucocorticoids were determined in male Sprague-Dawley rats following a single oral dose of mirex (100 mg/kg body wt). Mirex stimulated a significant elevation in plasma corticosterone levels 12 and 24 hr after dosing; however, hepatic tyrosine aminotransferase activity was not induced above control levels 6, 12, or 24 hr after mirex dosing. Mirex does not appear to directly inhibit the enzyme because tyrosine aminotransferase activity was increased in a dose-dependent manner in both intact and adrenalectomized rats when corticosterone supplements (1–50 mg/kg body wt) were given after mirex dosing. In an effort to explain the lack of hepatic TAT induction, the concentration of cytosolic binding sites for [ 3H]dexamethasone in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was measured 12, 24, and 48 hr after mirex dosing. There was a significant decrease in the total concentration of cytosolic binding sites for [ 3H]dexamethasone 12 and 48 hr after mirex dosing in intact rats, 12 and 48 hr after mirex dosing in adrenalectomized rats, and 12 and 24 hr after mirex dosing in adrenalectomized corticosterone-supplemented rats. There was a significant increase in the apparent dissociation constant ( K d ) in intact rats dosed with mirex as compared to the oil controls, but there was no difference in K d after mirex dosing in the adrenalectomized (ADX) rats when compared to the K d for the oil-dosed control rats. The maximal binding capacity ( B max) was not significantly different from oil controls after mirex dosing in either intact or ADX rats. The lack of hepatic TAT induction in the presence of increased plasma levels of corticosterone appears to be related to glucocorticoid receptor alterations in the liver of intact rats.

Tumor-Host Wasting Not Explained by Adrenal Hyperfunction in Tumor-Bearing Animals&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

This study addressed the question of whether hypercorticism in tumor-bearing animals contributes to the wasting of body fat and lean body mass, particularly that of skeletal muscles. For this purpose, hydrocortisone-substituted nongrowing sarcoma-bearing and control C57BL/6J mice were used that were either adrenalectomized or sham-operated prior to experimentation. Adrenalectomy in itself did not alter food intake or body composition in normal animals. Tumor-bearing mice and pair-weighted control animals had elevated urinary excretion of corticosteroids compared with the urinary excretion in freely fed controls. The malignant tumor induced the well-recognized wasting in tumor-bearing animals, irrespective of the presence of the adrenal glands. Therefore, an elevated corticosteroid production did not account for the wasting of body fat, lean body mass, skeletal muscle proteins, or decreased RNA activity in quadriceps muscles from tumor-bearing animals, although such muscles were sensitive to physiologic doses of injected hydrocortisone (20 micrograms/day). Tyrosine aminotransferase (TAT) activity in liver tissue from tumor-bearing animals was higher than that induced by pharmacologic doses of hydrocortisone in normal animals. Physiologic doses of hydrocortisone induced hepatic TAT activity, but pair-weighed control animals with the same degree of hypercorticism as was found in tumor-bearing animals had normal TAT activity in liver tissue. Although hypercorticism is present in tumor-bearing animals, the results demonstrate that cancer cachexia can start and proceed independently of the adrenal glands. Therefore, adrenal hyperfunction is not the proximate cause for the development of experimental cancer cachexia induced by anorexia.

Growth, body composition and hepatic tyrosine aminotransferase activity in cortisol‐fed channel catfish, Ictalurus punctatus Rafinesque

Metabolic consequences of chronic elevation of cortisol in the diet of yearling channel catfish, Ictalurus punctatus, were studied. Cortisol was incorporated into the diet in concentrations of 1, 10, 50 and 100 μg/g of food. This diet was offered at 3% of the body weight per day for 10 weeks. Fish were individually weighed and measured at 2‐week intervals and feeding rates were adjusted. Body weight, liposomatic index and condition factor were significantly lower and food conversion was significantly higher in fish fed 50 or 100 μng cortisol/g of food when compared with controls. The hepatosomatic index of fish fed cortisol at the rate of 100 μg/g of food decreased significantly. Specific activity of hepatic tyrosine aminotransferase was significantly higher at the two highest cortisol doses. Long‐term cortisol administration can reduce growth and condition factor by activating gluconeogenic mechanisms in which lipids and amino acids, rather than carbohydrates, are used for energy production. The metabolic effects of exogenous cortisol in this study offer an explanation for the decreased growth of fish under conditions that activate the secretion of endogenous cortisol.

Morphine inhibition of the insulin-inducible form of hepatic tyrosine aminotransferase

Morphine treatment in normal intact rats caused a dose-dependent increase in hepatic tyrosine aminotransferase (TAT) activity, as demonstrable up to 2 hr of exposure to the opioid alkaloid. However, such increase in TAT activity was invariably preceded by a prior decline in the enzyme level, as observed after 15 min of morphine treatment. Such an initial decline in activity was not demonstrable in diabetic animals. Further studies indicate that morphine inhibited the insulin-induced increase in TAT activity, a phenomenon which could be reversed by the opioid antagonist naloxone. The results suggest an opioid control mechanism in the regulation of the insulin-inducible form of TAT and indicate the possibilities of a trophic role of endogenous opiates in gluconeogenesis.