Effects of Hypophysectomy and Growth Hormone Treatment on Sex-Specific Forms of Cytochrome P-450 in Relation to Drug and Steroid Metabolisms in Rat Liver Microsomes

Yamazoe, Yasushi; Shimada, M.; Kamataki, Tetsuya; Kato, Ryuichi

doi:10.1254/jjp.42.371

Cited by 55 publications

(12 citation statements)

References 40 publications

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“…Microsomes and total RNAs were prepared 20 h after the last dose. Microsomes were prepared as previously described (Yamazoe et al, 1986). Intestinal mucosa microsomes were prepared as follows.…”

Section: Methodsmentioning

confidence: 99%

Isolation and Characterization of a New Major Intestinal CYP3A Form, CYP3A62, in the Rat

Matsubara

Kim²,

Miyata³

et al. 2004

J Pharmacol Exp Ther

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Based on information of the nucleotide sequence obtained from rat genome clones, a new CYP3A (CYP3A62) cDNA was isolated from the cDNA library of a rat liver. The CYP3A62 cDNA was 1746 base pairs (bp) in length, which included 1491 bp of an open reading frame and 93 bp and 209 bp of the respective 5Ј-and 3Ј-noncoding regions. Amino acid sequence deduced from CYP3A62 cDNA shared the highest similarity with rat CYP3A9 (79.9%) among human and rat CYP3A forms previously reported. CYP3A62 mRNA and protein were consistently detected in small intestines as well as livers. CYP3A62 was a major form in small intestines of both sexes but was a female-predominant form in livers of adult rats. CYP3A62 in both tissues of male and female rats were clearly enhanced by the treatment with dexamethasone. These expression profiles resembled those of CYP3A9. Despite clear detection of CYP3A62, no detectable levels of CYP3A1 and CYP3A2 proteins, as well as those of mRNAs, were found in the intestinal tract. Therefore, CYP3A62 may play major roles together with CYP3A9 and CYP3A18 in endogenous or exogenous detoxification at the absorption site.

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Section: Methodsmentioning

confidence: 99%

Isolation and Characterization of a New Major Intestinal CYP3A Form, CYP3A62, in the Rat

Matsubara

Kim²,

Miyata³

et al. 2004

J Pharmacol Exp Ther

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“…Western Blotting. Microsomal fractions were prepared from the rat livers and adipose tissues as described previously (Yamazoe et al, 1986). To remove the lipid layer effectively, the adipose homogenate in 1.15% KCl was first centrifuged at 2000g for 10 min, and the resultant middle layer (other than the upper lipid layer and pellet) was subjected to 9000g centrifugation.…”

Section: Methodsmentioning

confidence: 99%

Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue

Yoshinari¹,

Satô²,

Okino³

et al. 2004

J Pharmacol Exp Ther

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Lipophilic environmental pollutants are often stored in adipose tissues after exposure. These compounds have been well studied in terms of their cell toxicity in organs such as liver and kidney, and their xenoestrogenic action on reproductive tissues as endocrine disruptors. However, the effects of these chemicals on the depot, adipose tissue, have not been studied, although adipose tissue is an important endocrine tissue secreting obesity/diabetes-related hormones and cytokines. In this study, we identified the expression of cytochromes P450 in rat white adipose tissues and investigated the effects of typical lipophilic cytochrome P450 inducers, namely phenobarbital, dexamethasone, and ␤-naphthoflavone. The results showed that ␤-naphthoflavone was a strong CYP1A inducer in adipose tissue as well as in liver. It increased CYP1A1 mRNA, protein, and its related activity, ethoxyresorufin O-deethylase. Phenobarbital and dexamethasone also induced both the mRNA and protein of CYP2Bs and CYP3As, respectively, in adipose tissue, although significant interindividual differences were observed. Furthermore, we demonstrated that 48 h of fasting was as effective in adipose tissue as in the liver in the induction of CYP2E1 mRNA and protein. These results suggest that the mechanisms by which cytochrome P450 genes are regulated in the liver are also functional in rat adipose tissues. This has raised the possibility that lipophilic environmental contaminants accumulated in adipose tissue may dysregulate the gene expression profile.

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“…Some rats of SD strain were hypophysectomized or thyroidectomized at 7 weeks of age, and were supplemented with GH or thyroid hormone after 1 week of recovery. hGH was administered by twice-daily injection at 0.2 IU/100 g or by continuous infusion at 0.01 IU/h (22,23). T, was given by daily subcutaneous injection (5 or 50 n g/kg) for 7 days.…”

Section: Chemicals-35-diiodothyroninementioning

confidence: 99%

Hepatic Triiodothyronine Sulfation and Its Regulation by Growth Hormone and Triiodothyronine in Rats1

Gong

Murayama

Yamazoe

et al. 1992

The Journal of Biochemistry

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The regulatory mechanism of cytosolic sulfation of T3 has been studied in rat liver. Sulfation of T3 is sexually differentiated in adult rats of Sprague-Dawley (SD), Fisher 344, and ACI strains. In SD strain, the male animals showed 4 times higher sulfating activity than did the females. The specific activity was decreased by hypophysectomy of male adult rats, but was not affected in the females. Thus, the sex-difference was abolished in the hypophysectomized condition. Supplement of human GH intermittently twice daily for 7 days, to mimic the male secretory pattern, increased T3 sulfating activity in both sexes of hypophysectomized rats, whereas continuous infusion to mimic a female secretory pattern had no appreciable effect. Cytosolic sulfation of T3 was decreased by 25 to 30% by thyroidectomy or propylthiouracil treatment of male adult rats, and was restored by the supplementation of T3 (50 micrograms/kg daily for 7 days) to thyroidectomized rats. Administration of T3 in hypophysectomized rats almost completely restored the sulfating activity in the males and increased the activity in the females. Cytosolic T3 sulfation was inhibited by the addition of known inhibitors of phenol sulfotransferase, pentachlorophenol or 2,6-dichloro-4-nitrophenol. These results indicate a role of pituitary GH in hepatic sulfation of thyroid hormones in rats. The data obtained also raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers. T3 was also sulfated in hepatic cytosols of mouse, hamster, rabbit, dog, monkey, and human.(ABSTRACT TRUNCATED AT 250 WORDS)

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Effects of Hypophysectomy and Growth Hormone Treatment on Sex-Specific Forms of Cytochrome P-450 in Relation to Drug and Steroid Metabolisms in Rat Liver Microsomes

Cited by 55 publications

References 40 publications

Isolation and Characterization of a New Major Intestinal CYP3A Form, CYP3A62, in the Rat

Isolation and Characterization of a New Major Intestinal CYP3A Form, CYP3A62, in the Rat

Expression and Induction of Cytochromes P450 in Rat White Adipose Tissue

Hepatic Triiodothyronine Sulfation and Its Regulation by Growth Hormone and Triiodothyronine in Rats1

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