Development and regulation of bile salt sulfotransferase in rat liver

Chen, Lee J.; Kane, Bernard E.; Bujanover, Yoram; Thaler, Michael

doi:10.1016/0005-2760(82)90254-5

Cited by 15 publications

(13 citation statements)

References 17 publications

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“…These changes appear to be regulated by gonadal hormones in combination with pituitary hormones by complex interactions (Liu & Klaassen 1996). A similar pattern has been found with bile salt sulfotransferase in the rat, with enzyme activity increasing gradually from birth to puberty in both sexes, but in this instance male sulfotransferase activity drops dramatically at puberty while activity in the female is constant (Chen et al 1982).…”

Section: Sulfation By the Neonatal Rat Liversupporting

confidence: 80%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

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Section: Sulfation By the Neonatal Rat Liversupporting

confidence: 80%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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“…Estrogen enhanced bile salt sulfotransferase activity after only 2 days of treatment, which was much more rapid than previous studies using smaller daily doses for 1-4 wk (10)(11)(12)(13)(14)(15). This rapid enhancement of sulfotransferase activity by estrogen was blocked by actinomycin D and puromycin.…”

Section: Resultsmentioning

confidence: 54%

“…Age-related changes in bile salt sulfotransferase activity are observed during development in the rat; the sulfotransferase activity is very low in the fetal and newborn pups, but rises rapidly in the first weeks of life until a peak of activity at the time of weaning (6,10). Sex-related differences in activity develop after the onset of puberty, resulting in 3-fold greater sulfotransferase activity in mature females compared with males (6,(10)(11)(12).…”

mentioning

confidence: 99%

“…Sex-related differences in activity develop after the onset of puberty, resulting in 3-fold greater sulfotransferase activity in mature females compared with males (6,(10)(11)(12).…”

mentioning

confidence: 99%

“…Oophorectomy results in a decline in sulfation capacity in mature females, whereas treatment of males with ethinyl estradiol or estradiol benzoate for 10-42 days enhances sulfotransferase activity (10)(11)(12)(13)(14). The estrogen stimulation of bile salt sulfotransferase activity occurs with doses that do not cause cholestasis, and this enhanced activity correlates with the increased excretion of bile salt sulfates in bile (11,15).…”

mentioning

confidence: 99%

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Sexual Differentiation of Rat Hepatic Bile Salt Sulfotransferase Isoenzymes

et al. 1988

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Regulation of Bile Salt Sulfotransferase Isoenzymes by Gonadal Hormones†

1984

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We studied the regulation of hepatic bile salt sulfotransferase activity by gonadal hormones and the effect of gonadal hormones on two bile salt sulfotransferase isoenzymes. Bile salt sulfotransferase enzyme activity was three times greater in the female than in the male rats. Oophorectomy significantly decreased bile salt sulfotransferase activity in the female, but orchidectomy had no effect on bile salt sulfotransferase activity in the male. Estrogen treatment of intact as well as orchidectomized males markedly stimulated the enzyme activity, while testosterone treatment of intact or oophorectomized females did not effect bile salt sulfotransferase activity. We concluded that the 3-fold greater activity in female rats is due to the striking stimulatory effect of estrogen on bile salt sulfotransferase activity, and the testosterone has little or no role in the sexually related differences in bile salt sulfotransferase activity in mature rats. These sex-related differences in bile salt sulfotransferase activity were investigated further using DEAE-Sephadex A50 ion-exchange chromatography of rat hepatic cytosol. Two bile salt sulfotransferase isoenzymes were identified both with an approximate molecular weight of 130,000. Bile salt sulfotransferase I eluted with 0.05 M NaCl, had an isoelectric point at pH 6.8, was stimulated by estrogen, and was responsible for 90% of total bile salt sulfotransferase activity in the mature female. Bile salt sulfotransferase II eluted with 0.14 M NaCl, had an isoelectric point at pH 5.3, was unresponsive to estrogen, and accounted for 75 to 80% of bile salt sulfotransferase activity in the mature male.(ABSTRACT TRUNCATED AT 250 WORDS)

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Development and regulation of bile salt sulfotransferase in rat liver

Cited by 15 publications

References 17 publications

Neonatal Hepatic Drug Elimination

Neonatal Hepatic Drug Elimination

Sexual Differentiation of Rat Hepatic Bile Salt Sulfotransferase Isoenzymes

Regulation of Bile Salt Sulfotransferase Isoenzymes by Gonadal Hormones†

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