Precocious development of UDP-glucuronyltransferase activity in chick-embryo liver after administration of adrenocorticotropic hormone and of certain 11beta-hydroxy corticosteroids.

1. Precocious development of UDP-glucuronyltransferase (EC 2.4.1.17) and of glucuronidation by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs precociously in chick-embryo liver after administration to the egg of mammalian adrenocorticotropic hormone, of Synacthen (a synthetic compound possessing adrenocorticotropic activity), or of certain corticosteroids possessing a hydroxy or an oxo group at C-11. 3. Corticosterone-dependent transferase development parallels the rise of infused corticosterone in plasma, but does not require the presence of embryo pituitary in ovo, and is demonstrable in embryo liver explants in vitro. 4. Competence of embryo liver transferase to respond to corticosterone (or dexamethasone) begins over days 13-14, the time of competence to respond to grafted pituitary gland. 5. The transferase appearing after treatment with corticosterone or adrenocorticotropic hormone, like that appearing after pituitary grafting or on natural development and unlike that from the untreated embryo, is markedly activated by membrane-perturbation procedures, suggesting it appears through induction, not activation. 6. Thyroxine and tri-iodothyronine accelerate transferase development after treatment with adrenocorticotropic hormone or corticosteroid to the rate seen after pituitary grafting. 7. A wide range of other hormones and steroids did not obviously influence transferase development in this system. 8. We suggest that grafted pituitary gland evokes precocious transferase development in embryo liver through production of adrenocorticotropic hormone and hence of the active corticosteroids; thyrotropin and thyroxine hasten the process. The role of this mechanism in the natural development of UDP-glucuronyltransferase is discussed.     

Respiratory enzymes in the heart and liver of the prenatal and postnatal rat

1. Heart and liver tissue samples were obtained from rats in various developmental stages from the 12-day-old embryo to the 120-day-old postnatal animal. 2. The body, heart and liver weights and percentage protein in the liver and heart of the prenatal and postnatal rat were determined. 3. The activities of NADH–, NADPH– and succinate–cytochrome c reductases and cytochrome oxidase were determined also. 4. The specific activities of all the enzymes increased in both heart and liver during late foetal development (16 days to term). The NADH– and succinate–cytochrome c-reductase activities in the heart increased threefold during the neonatal period (0 to 25 days post partum) and then remained constant to 120 days. All reductase activities increased in the liver three- to six-fold during the neonatal period. Cytochrome-oxidase activity in both tissues increased sixfold during this time but plateaued in the liver at 12 days rather than 25 days. 5. A sex difference was observed in NADH–cytochrome c-reductase activity in the liver. Up to 25 days post partum the activity was the same in both sexes, but from that time on the activity continued to increase in the female but remained unchanged in the male. 6. NADPH–cytochrome c-reductase activity increased only in the liver. 7. These results indicate that different electron-transport pathways predominate according to the tissue, developmental stage and sex of the animal.     

Altered sexual differentiation of hepatic uridine diphosphate glucuronyltransferase by neonatal hormone treatment in rats

The hepatic microsomal enzyme UDP-glucuronyltransferase undergoes a complex developmental pattern in which enzyme activity is first detectable on the 18th day of gestation in rats. Prepubertal activities are similar for males and females. However, postpubertal sexual differentiation of enzyme activity occurs in which male activities are twice those of females. Neonatal administration of testosterone propionate or diethylstilboestrol to intact animals resulted in lowered UDP-glucuronyltransferase activity in liver microsomal fractions of adult male rats, whereas no changes were observed in the adult females and prepubertal male and female animals. Neonatal administration of testosterone propionate and diethylstilboestrol adversely affected male reproductive-tract development as evidenced by decreased weights of testes, seminal vesicles and ventral prostate. Diethylstilboestrol also markedly decreased spermatogenesis. Hypophysectomy of adult male rats resulted in negative modulation of microsomal UDP-glucuronyltransferase and prevented the sexual differentiation of enzyme activity. In contrast hypophysectomy had no effect on female UDP-glucuronyltransferase activity. A pituitary transplant under the kidney capsule was not capable of reversing the enzyme effects of hypophysectomy, therefore suggesting that the male pituitary factor(s) responsible for positive modulation of UDP-glucuronyltransferase might be under hypothalamic control in the form of a releasing factor. Neonatal testosterone propionate and diethylstilboestrol administration apparently interfered with the normal sequence of postpubertal UDP-glucuronyltransferase sexual differentiation.     

Some features of mitochondria and fluffy layer in regenerating rat liver

1. Mitochondria and fluffy layer were prepared from control and regenerating rat liver. Differential and density-gradient centrifugation were used to fractionate the preparations, which were examined for protein content, density and the activity of cytochrome c oxidase, succinate dehydrogenase, NAD–isocitrate dehydrogenase and NADP–isocitrate dehydrogenase. 2. During regeneration the mitochondrial protein content of the liver fell by 18% from the control value of 18·4mg. of protein/g. of liver (wet wt.) and by 3 weeks had risen to 130% of the control value. It then declined slowly. 3. The fluffy-layer protein content (4·7mg./g. of liver) varied inversely as the mitochondrial content and increased by 70% in the early stages (10 days) of liver regeneration. The results suggest that fluffy layer may partially represent both partly formed and broken-down mitochondria. 4. NAD– and NADP–isocitrate dehydrogenases differed in their behaviour during liver regeneration. 5. The succinate-dehydrogenase and NADP–isocitrate-dehydrogenase activity of fluffy layer was high and rose during the early stages of liver regeneration (1 week). Succinate dehydrogenase and cytochrome c oxidase were concentrated in the lighter fluffy-layer particles 10 days to 3 weeks after partial hepatectomy. The significance of this with respect to mitochondrial formation is discussed. 6. Mitochondrial fractions possessed a certain degree of heterogeneity in enzymic activity when separated according to size and density. The mean density of heavy mitochondria was 1·198, light mitochondria 1·193. Fluffy layer was nearly homogeneous in control liver, but during regeneration considerable heterogeneity became evident. The significance of the heterogeneity is discussed.     

Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity

Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic–pituitary‐testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90–106 years. We found that 94% of men exhibited preserved hypothalamic–pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging‐related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic–pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.     

Developmental aspects of uridine diphosphate galactose 4-epimerase in rat intestine

Kinetic and developmental characteristics of rat intestinal UDP-galactose 4-epimerase activity have been examined. The enzyme in the adult rat had a V_max. value 2–3 times higher than that of the newborn animal, but the K_m values for the enzyme in the newborn and adult rat were the same (0.17mm). No differences in epimerase activity were found along the length of the jejuno-ileum of adult animals, but higher activity was detected in the lower portion of the villi and crypts. The specific activity of the enzyme in the newborn rat began to rise at about 17 days of age, reaching a peak at 29 days of age, and then became constant at adult values. Total epimerase activity in the newborn rat liver was 2–5 times higher than the total activity in the intestine, and total epimerase activity in the adult intestine was 3–4 times higher than the total activity in the liver. Cortisone injection did not enhance the increase of epimerase normally seen during development, but caused a decrease in activity of this enzyme in the jejunum in rats up to 17 days of age. After 17 days, cortisone treatment had no effect on epimerase activity.     

Development of uridine diphosphate-glucuronyltransferase activity in cultures of chick-embryo liver

1. The liver of the domestric fowl (Gallus gallus) remains capable of conjugating o-aminophenol with glucuronic acid after 8 days' culture. The pathway of o-aminophenyl glucuronide formation in cultured liver, as in fresh tissue, includes the enzyme UDP-glucuronyltransferase. 2. UDP-glucuronyltransferase activity in chick-embryo liver increases on culture from very low to adult values within 6-8 days. 3. The development of UDP-glucuronyltransferase activity in cultured chick-embryo liver requires certain serum factors in the medium. The requirements change with embryo age. Liver from embryos younger than 15 days develops enzyme activity equally well in media containing either foetal or adult serum; liver from embryos older than 16 days develops activity only with adult serum. The development of enzyme activity in liver from the older embryos appears to be stimulated by diffusible factors in adult serum and inhibited by diffusible factors in foetal serum. It is suggested that the stimulation and inhibition of enzyme formation by small, diffusible molecules may be part of the mechanism regulating UDP-glucuronyltransferase activity in vivo. 4. Liver from 19-day-old chick embryos cultured with foetal serum begins to develop UDP-glucuronyltransferase activity if transferred to an adult-serum medium. Its capacity to develop UDP-glucuronyltransferase activity in adult serum survives in a foetal-serum medium for at least 5 days, the longest period tested. 5. The activity of UDP-glucuronyltransferase reached in 19-day chick-embryo liver after 1 or 2 days with adult serum is maintained without further increase after transfer to a foetal-serum medium. After 3 days with adult serum UDP-glucuronyltransferase activity continues to increase when the tissue is transferred to a foetal-serum medium. Thus liver from 19-day-old embryos requires 3 days with adult serum before development of enzyme activity becomes independent of a continuous adult-serum environment.     

MICROBODIES IN EXPERIMENTALLY ALTERED CELLS : II. The Relationship of Microbody Proliferation to Endocrine Glands

The liver cells of intact male rats given ethyl-α-p-chlorophenoxyisobutyrate (CPIB) characteristically show a marked increase in microbodies and in catalase activity, while those of intact female rats do not. In castrated males given estradiol benzoate and CPIB the increase in catalase activity and microbody proliferation is abolished, while in castrated females given testosterone propionate and CPIB the livers show a marked increase in microbodies and in catalase activity. No sex difference in microbody and catalase response is apparent in fetal and neonatal rats. Both sexes show a sharp rise in catalase activity on the day of birth, with a rapid decline at 5 days after birth. Thyroidectomy abolishes the hypolipidemic effect of CPIB in rats, but microbody proliferation and increase in catalase activity persists in thyroidectomized male rats, indicating that microbody proliferation can be independent of hypolipidemia. Adrenalectomy does not alter appreciably the microbody-catalase response to CPIB. These experiments demonstrate that (1) in adult rats, hepatic microbody proliferation is dependent to a significant degree upon male sex hormone but is largely independent of thyroid or adrenal gland hormones; (2) hepatic microbody proliferation is independent of the hypolipidemic effect of CPIB; (3) displacement of thyroxine from serum protein may not be sufficient cause for stimulation of microbody formation.     

Effect of n-hexane inhalation on the monooxygenase system in mice liver microsomes

When mice are continuously exposed to an atmosphere containing 2.5–3% n-hexane over a period of 4 days liver growth is observed after 24 h. Concomitantly the specific activities of cytochrome P450 and the cytochrome P450 reductase increase with a maximum after 38 h. The cytochrome b₅ levels in liver microsomes begin to rise at the second day and continue to increase even after the fourth day. No strict correlation is observed between the cytochrome P4SO content and the monooxygenation activity for cyclohexane. The pattern of hydroxylation products from n-hexane changes significantly upon pretreatment of the animals, suggesting that a qualitative alteration in the cytochrome P450 species had occurred.     

Spectrophotometric Studies on Intact Muscle : II. Recovery from contractile activity

The kinetics of the mitochondrial respiratory chain of intact muscle and the concomitant changes of the intercellular pH were investigated. Addition of lactate and pyruvate under resting conditions produces reductions of DPN and cytochrome b, and, occasionally, of cytochrome c and flavoprotein. Succinate gives similar but smaller changes. In recently excised muscles moderate contractile activity produces a reduction of cytochrome c and oxidations of DPNH, cytochrome b, and sometimes of the flavoproteins. Tetanic contractions and larger numbers of twitches produce reductions of DPN and of cytochromes b and c. In sartorii of the tropical toad, stored for approximately 2 days at 0–3°C, contractile activity always gives rise to long lasting oxidations of DPNH and cytochrome b. Addition of pyruvate or lactate shortens these oxidation cycles with a concomitant reduction of cytochrome c. These responses to contractions agree with those of mitochondria isolated from leg muscles of the toad upon the addition of ADP. Apparently the mitochondria in resting, excised muscles are not supplied with an excess of substrate. Measurements on the intercellular pH showed that even limited activity ( < 5 twitches) initiates glycolysis. The primary control of respiration resides, nevertheless, in the ADP concentration, rather than in the levels of substrate or inorganic phosphate. The results are quantitatively consistent with the view that ATP is the primary energy donor for muscular contraction.     

Asymmetric distribution of cytochrome P-450 and NADPH–cytochrome P-450 (cytochrome c) reductase in vesicles from smooth endoplasmic reticulum of rat liver

1. The topography of cytochrome P-450 in vesicles from smooth endoplasmic reticulum of rat liver has been examined. Approx. 50% of the cytochrome is directly accessible to the action of trypsin in intact vesicles whereas the remainder is inaccessible and partitioned between luminal-facing or phospholipid-embedded loci. Analysis by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis reveals three major species of the cytochrome. Of these, the variant with a mol.wt. of 52000 is induced by phenobarbitone and this species is susceptible to trypsin. 2. After trypsin treatment of smooth membrane, some NADPH–cytochrome P-450 (cytochrome c) reductase activity remains and this remaining activity is enhanced by treatment with 0.05% deoxycholate, which renders the membranes permeable to macromolecules. In non-trypsin-treated control membranes the reductase activity is increased to a similar extent. These observations suggest an asymmetric distribution of NADPH–cytochrome P-450 (cytochrome c) reductase in the membrane. 3. As compared with dithionite, NADPH reduces only 44% of the cytochrome P-450 present in intact membranes. After tryptic digestion, none of the remaining cytochrome P-450 is reducible by NADPH. 4. In the presence of both a superoxide-generating system (xanthine plus xanthine oxidase) and NADPH, all the cytochrome P-450 in intact membrane (as judged by dithionite reducibility) is reduced. The cytochrome P-450 remaining after trypsin treatment of smooth vesicles cannot be reduced by this method. 5. The superoxide-dependent reduction of cytochrome P-450 is prevented by treatment of the membranes with mersalyl, which inhibits NADPH–cytochrome P-450 (cytochrome c) reductase. Thus the effect of superoxide may involve NADPH–cytochrome P-450 reductase and cytosolically orientated membrane factor(s).     

Studies on the development of ornithine–keto acid aminotransferase activity in rat liver

1. During the normal development of the rat, the specific activity of liver ornithine–keto acid aminotransferase exhibits a transient elevation around term, and subsequently increases to adult activity levels during the third postnatal week. 2. The synthetic glucocorticoid triamcinolone, administered as a single injection, produces a marked elevation of the ornithine–keto acid aminotransferase activity within 24hr. if given postnatally before the natural increase in ornithine–keto acid aminotransferase activity has occurred. In foetal and adult animals, triamcinolone does not induce any increase in this enzyme activity. 3. The repeated administration of puromycin completely prevents the rise in ornithine–keto acid aminotransferase activity that follows triamcinolone administration. 4. If adult rats are fed with a protein-free carbohydrate diet, or one free of arginine, the ornithine–keto acid aminotransferase activity diminishes to a fraction of the normal. When such diets are given, a single injection of triamcinolone does not increase the enzyme activity within 24hr. 5. Partial hepatectomy, and repeated injections of growth hormone, depress the ornithine–keto acid aminotransferase activity in adult rats. 6. The findings are discussed in relation to the mechanisms concerned with developmental and adaptive changes in enzyme activities in the liver.     

Studies on sex-organ development. Effect of hormones on ornithine decarboxylase activity in the developing chick ovary

The response of ornithine decarboxylase activity to hormones in the embryonic left ovary was measured throughout the stages of development. During the early stage of ovarian development (9th day of incubation), the ornithine decarboxylase activity (in terms of pmol CO₂/30min per mg of protein) was high (766); it decreased from the 10th to the 12th day (575–239), increased slightly from the 13th to the 15th day (306) and finally fell to a low value (192–20) from the 18th day of development to birth. Administration of an optimal dose of oestrogen to the 9–10-day embryo stimulated the ovarian ornithine decarboxylase activity by 48–53%. If the same dose of oestrogen was administered to the 15–18-day embryo, the ovarian enzyme activity was suppressed by 32–43%. This biphasic response to oestrogen for enzyme induction is characteristic of the developing ovary and is not observed in other genital organs of the chick. In the early developmental stage (9–10th day) testosterone has no effect on ovarian ornithine decarboxylase activity, but in the late stage testosterone inhibits the activity by 41%. Organ culture techniques have been used to test the ovarian response to lutropin (luteinizing hormone). Lutropin stimulated ornithine decarboxylase activity by approx. 99–155% in the ovary of the early embryonic stage (10–13th day), and by 175–200% in the ovary of the late embryonic stage (15–18th day). The alteration in enzyme activity in the ovary as assayed in vitro during development is not due to the effect of the size of the endogenous ornithine pool. The relationship of ornithine decarboxylase activity to the morphological and biochemical changes in the developing ovary is discussed.     

Biochemical heterogeneity of rat liver mitochondria separated by rate zonal centrifugation

1. Rat liver mitochondria were separated on the basis of their sedimentation coefficients in an iso-osmotic gradient of Ficoll–sucrose by rate zonal centrifugation. The fractions (33, each of 40ml) were collected in order of decreasing density. Fractions were analysed by spectral analysis to determine any differences in the concentrations of the cytochromes and by enzyme analyses to ascertain any differences in the activities of NADH dehydrogenase, succinate dehydrogenase and α-glycerophosphate dehydrogenase. 2. When plotted as% of the highest specific concentration, the contents of cytochrome a+a₃ and cytochrome c+c₁ were constant in all fractions but cytochrome b was only 65% of its maximal concentration in fraction 7 and increased with subsequent fractions. As a result, the cytochrome b/cytochrome a+a₃ ratio almost doubled between fractions 7 and 25 whereas the cytochrome c+c₁/cytochrome a+a₃ ratio was unchanged. 3. Expression of the dehydrogenase activities as% of highest specific activity showed the following for fractions 6–26: NADH dehydrogenase activity remained fairly constant in all fractions; succinate dehydrogenase activity was 62% in fraction 6 and increased steadily to its maximum in fraction 18 and then decreased; the activity of α-glycerophosphate dehydrogenase was only 53% in fraction 6 and increased slowly to its peak in fractions 22 and 24. 4. These differences did not result from damaged or fragmented mitochondria or from microsomal contamination. 5. These results demonstrate that isolated liver mitochondria are biochemically heterogeneous. The importance of using a system for separating biochemically different mitochondria in studies of mitochondrial biogenesis is discussed.     

Stimulation of ornithine decarboxylase activity in rat tissues by growth hormone and by serum growth factor from rats infested with spargana of Spirometra mansonoides

Ornithine decarboxylase activity was studied in heart, kidney, liver, thymus, lung, spleen, skeletal muscle and fat of hypophysectomized rats after growth hormone treatment. A marked increase in enzyme activity was observed in kidney and liver, and a significant increase in heart and thymus at 4 h after injection of growth hormone. The kidney was the most responsive organ with an increase in activity of about 100 fold. The enzyme activity in kidney responded to a dose of 10 μg of growth hormone. Daily injection for 12 days raised activity only in the heart. Infestation for 6–13 days with spargana of Spirometra mansonoides, which also causes growth of hypophysectomized rats, increased enzyme activity in the heart and thymus. Intravenous injection of serum of hypophysectomized rats infested with spargana of Spirometra mansonoides caused a significant increase in the enzyme activity in liver and kidney after 4 h. Growth hormone and the serum growth factor of sparganosis seem to share the characteristic of causing an early increase in ornithine decarboxylase activity in rat tissues. The marked response in kidney and liver raises the possibility that these organs are the primary targets of both substances.     

Reconstitution of purified Wistar rat liver bilirubin UDP-glucuronyltransferase into Gunn-rat liver microsomes.

1. Reconstitution of purified bilirubin UDP-glucuronyltransferase from Wistar-rat liver into Gunn-rat liver microsomes provides a better environment than phosphatidylcholine liposomes, such that the final specific activity of the Wistar-rat liver enzyme was increased up to 85 units/mg of protein. 2. Gunn- and Wistar-rat liver microsomes were equally effective for reconstitution of the purified enzyme. 3. The transferase activity does not appear to be fully expressed in the more rigid environment of foetal Wistar-rat liver microsomes. 4. These reconstitution experiments reveal a final specific activity for the purified bilirubin UDP-glucuronyltransferase consistent with the capacity of the whole rat liver to glucuronidate bilirubin and indicate that the absence of this enzyme activity in Gunn-rat liver microsomes is not due to an abnormal microenvironment.     

Oestrogen-induced cholesterol and fatty acid biosynthesis in Xenopus laevis liver during vitellogenic response

1. Oestradiol-17β induces livers of Xenopus laevis (South African clawed toad) to synthesize and secrete into the serum large quantities of the egg-yolk-protein precursor, vitellogenin. The peak of this response occurs 9–16 days after hormone treatment [Dolphin, Ansari, Lazier, Munday & Akhtar (1971) Biochem. J. 124, 751–758]. It is now shown that 6 days after hormone treatment a 120–160-fold stimulation of the synthesis of cholesterol and fatty acid compared with control values occurred. 2. A cell-free system, derived from Xenopus liver, which synthesizes squalene and fatty acid is described. By using this system, several hundredfold stimulation of incorporation of [¹⁴C]acetate into squalene was recorded 6 days after the administration of oestradiol-17β, compared with a 3–4-fold stimulation of incorporation of [³H]mevalonate compared with control values. It is argued that oestradiol-17β must affect enzyme(s) catalysing step(s) between acetate and mevalonate in the biosynthetic pathway to cholesterol. 3. In incubation of liver slices in vitro, most of the lipid and cholesterol synthesized in response to the steroid hormone was associated with those subcellular fractions that contained membranes. Moreover, pulse-labelling experiments in vivo showed that 70% of this lipid and cholesterol was retained in the liver. The remainder appeared in the serum, where it was equally distributed between vitellogenin and vitellogenin-free serum. 4. G.l.c. analyses of the cholesterol content of liver microsomal fractions of Xenopus laevis indicated that the cholesterol content was at least 50% higher in microsomal fractions obtained from livers that had been exposed to oestradiol-17β. Meanwhile, g.l.c. analysis of the lipid moiety of secreted vitellogenin showed that up to 35% of its lipid was cholesterol.     

Immunocytochemical studies of chicken somatotrophs and somatotroph granules before and after hatching

Immunocytochemical methods were used to gain information about the embryonic development of chicken somatotrophs before and after hatching. To localize growth hormone, anterior pituitary sections were incubated with growth-hormone antibody, and then an indirect peroxidase method was used for light microscopy and an immunogold method for electron microscopy. The earliest evidence of embryonic somatotrophs was seen at 12 days. At this stage somatotrophs were sparse (0.2% of parenchymal cells) and their granules were pleomorphic with elongated ovoid and lozenge shapes predominating. Few of the immunogold-labeled somatotroph granules of the embryo were spherical until 15 days after fertilization. At 18 days, most of the granules were spherical (their shape in the adult chicken). During the six days between the 15-day-old embryo and the 1-day-old chick, the number of gold particles per granule section approximately doubled suggesting an increase in growth hormone content of the granules. This rise was the result of increases in the size of the granule sections and in the concentration of gold particles in the sections. During the embryonic period of 12–20 days, somatotrophs were not more than 3.6% of the anterior pituitary cell population. During the following two days, between the 20-day-old embryo and the 1-day-old chick, the percentage of somatotrophs in the pituitary parenchymal cell population rose rapidly from 3.6% to 20.7% and then increased slowly to 24.6% during the period of 1–5 days after hatching. Both the sharp percentage rise in somatotrophs (20-day-old embryo to 1-day-old chick) and the rise in growth hormone content of the granules (15-day-old embryo to 1-day-old chick) suggested by gold-particle counts occur close to the time of hatching. These morphological changes may reflect an increased synthesis of growth hormone that is responsible for the rise in plasma growth-hormone concentration that begins about the same time and is especially abrupt two days later (1–3 days after hatching).     

Stimulation by secretin of bilirubin UDP-glycosyltransferase activities and of cytochrome P-450 concentration in rat liver.

The activity of bilirubin UDP-glucuronyltransferase in liver tissue was increased 1.5-fold after 90 min of secretion administration (4 i.u./h per kg body wt.) in anaesthetized Wistar rats biopsied half-hourly over a period of 2 h. In unanaesthetized R/A Wistar rats, activities of liver enzymes were assayed after administration secretin for 1 h. Bilirubin UDP-glycosyltransferase activities and cytochrome P-450 concentration were increased, but p-nitrophenol UDP-glucuronyltransferase and UDP-glucose dehydrogenase activities remained unchanged.