Activity In Male Rats Research Articles

Structural requirements of some sulphonamides that possess an antifertility activity in male rats

Sulphonamides with different chemical structures were synthesized and these 13 compounds together with 7 commercially available sulpha drugs were tested for antifertility activity by natural mating in male rats. All compounds were given daily by gastric intubation at doses of 125, 150, 250 or 450 mg/kg for 6 weeks. Sulphapyridine caused a dose-related and reversible reduction in fertility at doses between 125 and 450 mg/kg. At the high dose, fertility was reduced to 25.9% of control at 5 weeks after treatment, and complete recovery occurred by 3 weeks after drug withdrawal. This activity was abolished when the pyridine ring was substituted by other heterocyclic rings, except sulphachloropyridazine which had only weak activity. Replacement of the pyridine ring by a hydrogen atom or short aliphatic chains preserved or even enhanced the potency. Thus, sulphanilamide, N1-methylsulphanilamide or N1-diethylsulphanilamide produced a marked but reversible reduction in fertility. Removal or substitution of the N4-amino group on the benzene ring of sulphapyridine with a methyl group destroyed the activity. However, the bromo or nitro analogue (at the para- but not the meta-position of the benzene ring) still possessed some activity. N4-Acetyl derivatives of sulphapyridine, sulphanilamide, and N1-diethylsulphanilamide were as potent as their parent compounds. These results suggest that the presence of pyridine or other heterocyclic rings is not necessary for the antifertility activity of sulphonamide compounds. However, the N4-amino group is indispensable. In addition, acetylation of this amino group does not change the potency. The prototype of the antifertility sulphonamides therefore seems to be sulphanilamide.

Renal 11β-hydroxysteroid dehydrogenase activity: Effects of age, sex and altered hormonal status

The enzyme 11β-hydroxysteroid dehydrogenase, by converting cortisol and corticosterone to their receptor-inactive 11-keto metabolites cortisone and 11-dehydrocorticosterone, appears crucial to the aldosterone-selectivity of renal mineralocorticoid receptors. Levels of enzyme activity in the rat kidney, measured by conversion of cortisol to cortisone, are unaltered by changes in adrenal or thyroid status, or by castration in either sex; in contrast, oestrogen administration increases enzyme activity in male rats.

老化と薬物の代謝 : 機能低下か雌化か.雄ラット肝の薬物代謝能の加齢変動

The profiles of hepatic drug metabolism were obtained by using young and old male and female rats. The profile obtained from old male rats was completely different from that from young male rats, while it was almost identical to those of females of any ages. This was due to the selective decrease in male hepatic enzyme activities showing higher activities than females to the activity levels of females which did not alter much with aging. Castration of young adult male rats caused a decrease in enzyme activities but did not result in the feminization of the metabolic profile. Administration of testosterone to old male rats resulted in the recovery of the profile of young male rats, but the levels of activities were not as high as young male rats. Plasma testosterone levels were found to decrease in parallel with drug metabolizing activities of male rats during aging. These results suggest that sex hormones play important roles in the alteration of drug metabolizing activities in male rats with aging. The loss of male characteristics in profile of drug metabolism during aging was evaluated by use of antibody to the male specific cytochrome P-450, P-450 m1. Anti-P-450 ml strongly inhibited imipramine N-demethylase activity, which showed marked sex (male greater than female) and age (young greater than old) differences, while this did not inhibit imipramine 2-hydroxylase activity, which showed no sex or age differences. The portion of N-demethylase activity inhibited by this antibody decreased in old rats while the portion not inhibited did not decrease with age. These results indicate that the decrease of sex specific cytochrome P-450 is responsible for the age-associated decrease in at least one of the drug metabolizing enzyme activities in male rats. It is suggested that some processes of the control mechanism of the gene expression of male specific cytochrome P-450 may be altered with old age.

Effects of emulsified perfluorochemicals on liver aryl esterase in rats

1. The effects of intravenous (i.v.) injection of various perfluorochemical (PFC) emulsions have been studied separately in male and female rats. 2. Injection of 10 ml/kg body weight of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding change occured in response to injection of Oxypherol (FC-43). 3. Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43. 4. Mean liver aryl esterase activity in male rats was increased 2- to 3-fold ( P < 0.05) at 7 days a injection of the novel emulsion. No significant alterations in aryl esterase activity occurred in respons to injection of either F-DA or FC-43, although in both cases there was a trend towards increased activity 5. Liver aryl esterase activity in female rats was significantly ( P < 0.05) decreased at 72 hr foll FC-43 injection with similar, but much less pronounced, changes occurring in response to injection of F-DA and the novel emulsion. 6. These results show that injection of a single low dose of emulsified PFCs into rats can alter hepatic microsomal aryl esterase activity but the response is highly variable, depending on composition of emulsion injected and sex of recipient.

Pharmacokinetic studies of mofezolac. III: Differences of metabolic pathways brought by animal differences.

We studied the factors related to species and sex difference contributing to metabolic patterns of[3, 4-di(4-methoxyphenyl)-5-isoxazolyl] acetic acid (mofezolac) in vitro, and the metabolic pathway determined after administrations of metabolites of mofezolac. Also the metabolism of mofezolac in germ free rats, and the in situ absorption rates using recirculation perfusion of mofezolac and the metabolites were studied.1. Mofezolac demethylase activities in monkeys and rats were highest among investigated animals, following by the activity in mice. The activity in the dog was about 10 times lower than that in mice. Sex difference in mofezolac demethylase activity was not observed in the rats. UDP-glucuronatemofezolac glucuronosyltransferase activities in the monkey and the dog were high, and that in the rat was about 1/3 lower than that in the monkey and the dog.2. Mofezolac sulfotransferase activity in rats cytosol was much higher than the activities in other investigated animals. Sex deference was observed in rats ; the activity in male rats was about 3 times higher than that in female rats. Therefore, the total amount of sulfoconjugate of[3-(4-hydroxyphenyl)-4-(4-methoxyphenyl)-5-isoxazolyl] acetic acid(3-DM-mofezolac) in vivo reflects the sulfotransferase activity of liver.3. After administrations of mofezolac metabolites, the main metabolite in bile derived from 3-DM-mofezolac was 4-[4-(4-methoxyphenyl)-5-carboxymethyl-3-isoxazolyl] phenyl hydrogeo sulfate (3-DM-mofezolac-sulfate), and the main metabolite derived from[4-(4-hydroxyphenyl)-3-(4-methoxyphenyl)-5-isoxazolyl]acetic acid (4-DM-mofezolac) was[3, 4-di(hydroxyphenyl)-5-isoxazolyl] acetic acid (3, 4-DM -mofezolac-sulfate). These results explain that 3-(4-methoxyphenyl) was desmethylated easier than 4-(4-methoxyphenyl). No sulfoconjugate of 4-DM-mofezolac was formed after administration of 4-DM-mofezolac. This result suggested that sulfoconjugate was not formed by binding of a sulfate directly to OH in the phenyl group on the side of 4-position of isoxazol.4. The main fecal metabolite in SPF rats was 3-DM-mofezolac, while in germ free rats was 3-DM-mofezolac-sulfate. This result clarified that 3-DM-mofezolac-sulfate was degraded by intestinal microflora.5. The absorption rate constant of mofezolac from the small intestine was close to the absorption rate constants of indomethacin or salicylic acid using in situ recirculation perfusion system. In the stomach, mofezolac was absorbed in about 1/2 of that in small intestine when the perfusate was acidic (pH3). The absorption rate constant of 3-DMmofezolac-sulfate was about 8 times lower than the that of mofezolac. 3-DM-mofezolacsulfate was hardly absorbed.

Effect of parathyroid hormone, centrally or peripherally injected, on gastric activity in male rats

Parathyroid hormone (PTH) injected peripherally did not interfere with the development of experimental ulcers. Conversely, when PTH was administered i.c.v. the development of ulcers was significantly inhibited. The gastric secretory volume and acid output were also reduced. The possibility is discussed that this antisecretory activity of PTH may be due to a direct effect at the CNS level.

Effects of (±)3,4-methylenedioxymethamphetamine (MDMA) on brain dopaminergic activity in rats

Acute treatment with (±)3,4-methylenedioxymethamphetamine (MDMA) at high doses (10 and 30 mg/kg, IP), but not lower doses increased locomotor activity in male rats. MDMA did not consistently produce any other stereotyped behaviors at any dose. Dopamine (DA) turnover rate as estimated by the ratio of brain tissue levels of 3,4-dihydroxyphenylacetic acid (DOPAC) over DA was decreased in the striatum for up to two hours after acute treatment with 10 mg/kg of MDMA. DA turnover rate was inconsistently decreased in the olfactory tubercle and medial basal hypothalamus, and was unchanged in the medial prefrontal cortex and the substantia nigra/ventral tegmental area. Two hours after a 30 mg/kg injection of MDMA, DA turnover rate was decreased in all brain areas tested. MDMA and d-amphetamine partially reversed a haloperidol-induced elevation of striatal DOPAC levels. In contrast, the nonamphetamine stimulant, amfonelic acid, enhanced haloperidol's effect. In chloral hydrate-anesthesized rats, MDMA injected IV partially inhibited spontaneous firing rate of DA neurons in the substantia nigra (34% decrease at 4 mg/kg of MDMA). Seventeen days after subchronic MDMA treatment (10 or 20 mg/kg, IP, twice per day for four days), DA and DOPAC levels were unchaged in all brain areas tested as compared to levels in control rats. It is concluded that acute treatment with high but not low doses of MDMA has a weak amphetamine-like effect on nigrostriatal as well as mesolimbic/mesocortical and tuberoinfundibular DA neurons in rats. Repeated treatment with MDMA does not appear to be toxic to mesotelencephalic or tuberoinfundibular DA neurons.

Growth hormone regulation of hepatic drug-metabolizing enzymes in the mouse

Hepatic microsomal hexobarbital hydroxylase and aminopyrine N-demethylase activities increased in adult male mice following hypophysectomy to female-like levels, eliminating the normal sexually dimorphic pattern of these enzymes. Exogenous growth hormone replacement ( 0.08 I.U. 100 g body weight/day) re-established the lower masculine activities only when administered subcutaneously once every 12 hr. Enzyme activities remained elevated at female-like levels when the same total dose of growth hormone was infused continuously using osmotic pumps or was injected once every 6 hr. These data suggest that, despite the reversed orientation of sex differences in hepatic drug-metabolizing enzymes between rats and mice (i.e. higher enzyme activities in female mice and male rats), the basic hormonal regulatory axis is similar in the two species. Cyclic fluctuations of systemic growth hormone concentrations masculinize kinetic parameters of hepatic hexobarbital hydroxylase and aminopyrine N-demethylase in both species. Rats and mice differ in that these similar hormonal signals lower the apparent V max in male mice, while markedly increasing the enzyme activities in male rats. It appears more likely, therefore, that species- and sex-specific differences in the total hepatic cytochrome P-450 isoenzyme populations produce the reversed sex-dependent pattern of hexobarbital hydroxylase and aminopyrine N-demethylase.

Correlation between changes in LH-RH content in the synaptosomal fraction of the olfactory bulb and some hypothalamic zones and level of sexual activity in male rats

We have studied the level of LH-RH in the synaptosomal fraction of the olfactory bulbs, preoptic area, and mediobasal hypothalamus, and the blood level of HL in adult male rats with sexual activity after noradrenergic denervation of the preoptic area using 6-oxydopamine. A neurotoxic effect of a 0.1% solution of ascorbic acid, preventing 6-oxydopamine disintegration was observed. Both sexual activity and level of LH-RH in synaptosomes of the preoptic area were reduced in male rats with noradrenergic denervation of the preoptic area. The maximum blood level of LH was observed during exposure to a recipient female rat, the LH-RH concentration in the synaptosomal fraction of the olfactory bulbs being raised, and that in the mediobasal hypothalamus being decreased. The results showed that LH-RH synthesizing cerebral neurons with terminals in the olfactory bulbs, preoptic area, and mediobasal hypothalamus are involved in the regulation of sexual behavior and the interaction of LH-RH-containing terminals with noradrenergic nerve endings at the level of the preoptic area.

Effects of mutagenic and non-mutagenic aniline derivatives on rat liver drug-metabolizing enzymes.

1. The effect of 4,4'-methylene bis(2-chloroaniline) (MOCA), 4,4'-methylene dianiline (MDA) and 4,4'-sulphonyldianiline (Dapsone) in vivo on xenobiotic biotransformation in male rat liver was studied. 2. Treatment with MOCA or MDA but not Dapsone caused a dose-dependent increase in ethoxyresorufin O-deethylase activity and a concomitant decrease in aldrin epoxidase activity in male rats. 3. Treatment with MOCA or MDA resulted in dose-dependent increases in ethoxycoumarin O-deethylation and epoxide hydrolation, while only MOCA induced cytosolic glutathione S-transferase activity. 4. Treatment with Dapsone resulted in no changes in xenobiotic biotransformation except for the induction of aniline hydroxylation. 5. The results are consistent with the contention that there is a relationship between carcinogenic chemicals and particular alterations in the activities of biotransformation enzymes.

Rat strain variations in liver cytosolic DT-diaphorase activity and possible significance of the trait in carcinogenesis by azo dyes

1. 1. Strain variations among female rats in terms of cytosolic DT-diaphorase activity were studied in liver, heart and glandular stomach tissues with or without administration of 3- tert-butyl-4-hydroxyanisole (BHA). 2. 2. BHA induced liver DT-diaphorase activity in all strains examined, and both the basal and induced activities varied according to strain. Among the five strains tested, Brown Norway (BN) and Sprague-Dawley (SD) rats showed relatively high levels of enzyme activity in the liver, whereas Fischer (F344) rats showed a relatively low level of activity. Results of examination of Fischer-BN-F 1 rats indicated that a lower level of liver DT-diaphorase activity was inherited essentially as a dominant trait. 3. 3. Liver DT-diaphorase activity in male rats was significantly lower than in female rats. Small strain variations of the activity, if any, were observed in the heart and stomach cytosolic fractions with or without induction by BHA. The magnitude of induction by BHA was also small, if any, in heart and stomach cytosolic fractions. 4. 4. From these and other observations, we discussed the differences between rats and mice in these strain and tissue variations of DT-diaphorase activity, and also the possible significance of liver DT-diaphorase activity in carcinogenesis by azo dyes.

Modifications of the sexual activity in male rats following administration of antiserotoninergic drugs

The influence of cyproheptadine (CPH), methysergide and 5-hydroxytryptamine (5-HT) was studied on male sexual activity. Wistar rats from a colony of the Department were used. Measures of sexual parameters (number of ejaculations, initial latency, ejaculation latency, refractory period and neuromotor activity) indicate that cyproheptadine and methysergide facilitate male sexual activity. However, 5-HT inhibits male sexual reflex. Our experimental results suggest that the serotoninergic system exerts an inhibitory role on the sexual parameters which comprise the copulatory model of the male rat and also demonstrate that cyproheptadine facilitates sexual behavior of the male rat.

Peripubertal castration of male rats, adult open field ambulation and partner preference behavior

The validity of the hypothesis put forward earlier, that testicular secretions during puberty have an organizing effect on open field ambulation was examined. Male rats were castrated or sham-operated at days 21, 43 or 70. At the age of 17 weeks the males were tested in an automated, octagonal open field (3 consecutive days, 3 min/day) for locomotor activity. Male rats castrated at day 21 or day 43 ambulated more than sham-castrated controls. Males castrated at day 70 did not differ from sham-castrated controls. It thus appears that pubertal testicular secretion(s) organize adult open field locomotor activity in male rats. From 18 weeks of age partner preference behavior was tested in the same open field apparatus with one adjacent cage containing an ovariectomized female and an opposite one containing an ovariectomized female brought into heat. The females in the adjacent cages were separated from the experimental males in the octagonal cage by wire mesh. Peripubertally castrated males did not show a clear-cut partner preference, whereas the intact males preferred the vicinity of the estrous female. There were no differences among the males castrated either before, during or after puberty. Testosterone treatment (crystalline T in silastic capsules) caused peripubertally castrated males to prefer the estrous female. Thus, adult partner preference behavior does not seem to be organized by peripubertal testicular androgens.

Effect of sulfasalazine and its analogs on fertility in male rats

Several derivatives of sulfasalazine were tested for their antifertility activity in male rats. The compounds were administered to groups of rats daily by oral gavage for 28 days. Fertility of the rats treated with sulfasalazine or compound CH 74A was reduced, while other compounds had no effect. In a subsequent experiment, therefore, only the active compounds were studied further. Fertility of rats treated with sulfasalazine, compound CH 74A, CH 99A or sulfapyridine was reduced during 40 days of treatment. At the end of treatment, body weights were reduced in higher dose groups of sulfasalazine, CH 74A and sulfapyridine compared to control animals. The weights of the testes, prostate or seminal vesicle were not altered by any of the treatments. On the other hand, weight of the epididymides decreased in all higher dose groups except in CH 99A-treated animals. Sperm motility decreased in all the treated rats except in animals treated with low dose of sulfapyridine, whereas epididymal sperm count decreased in all but CH 99A-treated animals. These results suggest that sulfasalazine and its derivatives bring about their antifertility effects by decreasing sperm motility and/or number of spermatozoa.

Effect of age, gonadectomy and hypophysectomy on mitochondrial hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol in female and male rat liver.

In a previous study we found that liver mitochondrial side-chain hydroxylation of vitamin D3 (cholecalciferol) and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was higher in female than in male rats [Saarem & Pedersen (1987) Biochem. J. 247, 73-78]. The present paper describes the effects of age, gonadectomy and hypophysectomy on these activities. The sex difference became manifest above the age of 7 weeks. Ovariectomy and/or injection of oestradiol valerate had no effect on the hydroxylase activities in adult females. Castration increased, and subsequent testosterone treatment decreased, the hydroxylase activities in adult males. Hypophysectomy had no effect in females, but increased the hydroxylase activities in males. Testosterone treatment had no effect in hypophysectomized females or males. Injection of oestradiol valerate had no effect on the hydroxylase activities in hypophysectomized females. In hypophysectomized males this treatment had no effect on the vitamin D3 25-hydroxylase activity, but decreased the C27-steroid 27-hydroxylase activity in males. Microsomal 1 alpha-hydroxyvitamin D3 25-hydroxylase activity was lower in females than in males in all age groups. Castration or hypophysectomy decreased the activity in male rats. It is concluded that, in adult female rats, the mitochondrial side-chain hydroxylation of vitamin D3 and of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol is independent of sex hormones. In males these activities are regulated by influence of sex hormones on the hypophysis, probably by the presence of androgens in the neonatal period. Different effects on the two hydroxylases indicate the presence of at least two different cytochromes P-450 in rat liver mitochondria.

Trichlorobenzenes: Results of a Thirteen Week Feeding Study in the Rat

Trichlorobenzenes (TRCBs) are industrial chemicals and environmental pollutants found in Great Lakes fish. The present study was carried out to provide information on the toxic effects of these chemicals in mammals. Groups of male and female weanling rats were fed diets containing TRCB isomers at 1, 10, 100 or 1000 ppm for 13 weeks. The group of males fed 1000 ppm 1,2,3-TRCB diet had reduced weight gain. No other clinical signs of toxicity were observed. Increased relative liver and kidney weights occurred in the highest dose groups of males for all 3 TRCBs. Of the 3 isomers, only 1,2,4-TRCB at 1000 ppm caused increases in hepatic aminopyrine demethylase and aniline hydroxylase activities in male rats, and aminopyrine demethylase in females. Serum biochemical and hematological parameters measured were not affected. All three TRCBs produced histological changes of a moderate degree in the liver and thyroid of male rats at 1,000 ppm. Only 1,3,5-TRCB elicited moderate renal changes in male rats fed 1,000 ppm. Microscopic changes in the females were generally milder than those of the corresponding males. Based on these data it was concluded that the nonobservable adverse effect levels for the three TRCBs were 100 ppm in the diet, or 7.6 approximately 7.8 mg/kg b.w./day depending on the dietary consumption.

Chronic administration of tricyclic antidepressants suppresses hypothalamo-pituitary-adrenocortical activity in male rats

The effect of chronic administration of the clinically effective antidepressants, imipramine, clomipramine and desipramine, on corticosterone (CS) release in male rats was investigated. Chronic administration of imipramine, clomipramine and desipramine at a dose of 20 mg/kg b.w./day, but not at a dose of 2 mg/kg b.w./day, suppressed blood CS concentration at 2000h and abolished its circadian rhythm. The normal circadian rhythm of CS release resumed seven days after the termination of imipramine injection. The acute administration of imipramine (20 mg/kg b.w./day) at 0800h but not at 2000h elevated CS concentrations. Chronic administration of imipramine (20 mg/kg b.w./day) tended to increase the inhibitory effect of dexamethasone on CS release. Adrenocortical sensitivity to exogenous adrenocorticotropic hormone tended to be decreased by chronic administration of imipramine (20 mg/kg b.w./day). These results indicate that antidepressants have effects on the hypothalamo-pituitary-adrenocortical axis which may confound psychoneuroendocrinological tests, such as the dexamethasone suppression test, for the diagnosis of affective disorders.

Age-related release of prolactin by the pituitary and the pituitary-hypothalamic complex in vitro: an attempt to describe the development of the hypothalamic prolactin-inhibiting and -releasing activities in male rats

We have recently demonstrated that the pituitary hypothalamic complex (PHC) is a good model for studying interactions between the hypothalamus and pituitary in vitro. The amount of prolactin secreted by the PHC is an index of prolactin secreted by the pituitary in the presence of hypothalamic control, while the amount released by the whole pituitary alone is an index of prolactin secreted in the absence of hypothalamic control. The amount of prolactin secreted by the PHC has been regarded as an index of hypothalamic prolactin-releasing activity (HPRA), while the difference in the amounts of prolactin secreted by the whole pituitary and the PHC is the hypothalamic prolactin-inhibiting activity (HPIA). Attempts were made to correlate HPRA and HPIA to the development of serum concentrations of prolactin from days 7 to 77 in male rats. The HPRA increased steadily from days 7 to 56, decreased significantly on day 63 and thereafter remained unchanged until day 77. The HPIA was low on days 7 and 14 and increased steadily up to day 49, with no further significant variations. The developmental patterns of HPRA and HPIA were comparable up to day 49. Serum concentrations of prolactin increased significantly until day 28 and remained fairly constant until day 49. The weight of the pituitary gland increased from 1.0 +/- 0.03 mg (mean +/- S.E.M.) on day 7 to 7.76 +/- 0.32 mg on day 63 and remained unchanged thereafter. The weight of the hypothalamic islet was 31.5 +/- 2.88 mg on day 7, 34.83 +/- 1.45 mg on day 14 and 50.4 +/- 4.01 mg on day 21. After day 21 the weights of the hypothalamic islets were not significantly altered, except on day 49. It was concluded that serum concentrations of prolactin are regulated by interaction or competition between HPRA and HPIA at the level of the pituitary.

Androgens stimulate preoptic area Na +,K +-ATPase activity in male rats

This paper describes the effects of castration and testosterone replacement on the Na +,K +-ATPase activity levels of the cerebral cortex (CC), preoptic-suprachiasmatic region (POSC) and mediobasal hypothalamus (MBH) in male rats. Na +,K +-ATPase activity was estimated as the ouabain-sensitive fraction of ADP and AMP generation rate, measured by high-pressure liquid chromatography (HPLC) with UV detection, from a standard incubation mixture containing 3 mM ATP. Orchidectomy, performed 4 weeks before sacrifice, decreased ATPase activity of MBH. Testosterone propionate treatment (50 μg/day × 2 days) to castrated animals resulted in a 4-fold increase in enzyme activity in the POSC, an effect that might be related to the behavioral effects of androgens. None of the treatments seemed to influence the enzyme activity of the cerebral cortex.

The induction of a specific form of cytochrome P-450 (P-450j) by fasting

In previous work we have demonstrated that liver microsomal N -nitrosodimethylamine demethylase (NDMAd) activity is increased in rats by fasting, and we have postulated that this is due to the induction of a specific form of cytochrome P-450. This communication provides evidence for such a hypothesis. Fasting for 24 and 48 h caused 59 and 116% increases, respectively, in NDMAd activity in male rats, and fasting for 48 h caused a 63% increase in female rats. These increases were accompanied by corresponding increases of cytochrome P-450j (P-450ac) determined by immunoblotting. Fasting for 24 and 48 h also increased the mRNA for P-450j by 153 to 250%, as determined by hybridization with a cDNA probe of this cytochrome. The results suggest that fasting affects the gene expression of P-450j.