Sex Steroid Induced Changes in Hepatic Enzymes

Gustafsson, Jan‐Åke; Mode, Agneta; Norstedt, Gunnar; Skett, Paul

doi:10.1146/annurev.ph.45.030183.000411

Cited by 313 publications

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“…Moreover, the pituitary gland also plays an essential role in the sex-related differences in drug and steroid hydroxylations (18,19). Growth hormone has been postulated as a responsible factor (18,20,34,35).…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of catalytic activities, N-terminal amino acid sequences and other properties, P-450 2c, and P-450 5R and P-450i are probably identical with or have a close resemblance to P-450-male and P-450-female, respectively (12,17). On the other hand, the involvement of the pituitary gland in the occurrence of sex differ ences induced by gonadal hormones in drug and steroid metabolisms in rat liver micro somes has been demonstrated (3,(18)(19)(20). Growth hormone has been postulated to be the responsible factor in the pituitary gland.…”

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confidence: 95%

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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

Yamazoe

Shimada

Kamataki

et al. 1986

Japanese Journal of Pharmacology

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Abstract-Hypophysectomy decreased the content of a male specific cytochrome P-450, P-450-male, in male rats, while it expressed P-450-male and completely depressed a female specific cytochrome P-450, P-450-female, in female rats. Intermittent injections of human growth hormone (GH), which mimic the secretion in males, restored P-450-male in hypophysectomized (Hypox) male rats and partially restored P-450-female in Hypox female rats. Continuous infusion of GH, which mimics the female secretion pattern, into Hypox male rats caused a further decrease in P-450-male content, and it caused the expression of P-450-female. In Hypox female rats, the same treatment depressed P-450-male and expressed P-450-female to the level of an intact female. These results indicate that the diurnal changes in the pattern of serum growth hormone level regulate the expression of P-450-male and P-450-female. The activities of testosterone 2a and 16a hydroxylases were closely correlated to P-450-male content with the correlation coefficients (r) of 0.955 and 0.929, respectively. Benzo(a)pyrene hydroxylation was also correlated to P-450-male content (r=0.850).Aminopyrine N-deme thylation and propoxycoumarin 0-depropylation were correlated to less extents (r=0.692 and r=0.720), while aniline hydroxylation and 0-ethylresorufin 0 deethylation were not correlated to P-450-male content. These results indicate that testosterone 2a and 16a-hydroxylations are closely dependent, but the metabolism of a variety of drugs are dependent to different extents on P-450-male in rat liver microsomes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

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

Shimada

Kamataki

et al. 1986

Japanese Journal of Pharmacology

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“…Administration of estrogens to male rats can result in feminization of sexually dimorphic liver function (reviewed in References 7 and 8). This effect presumably results from feminization of sexually dimorphic patterns of pituitary growth hormone secretion, as growth hormone appears to be the predominant determinant of sexually dimorphic patterns of hepatic enzymes and receptors (7,8,31).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Ultimate control over these sex differences in hepatic function resides in the pituitary gland. In particular, growth hormone secretion patterns, also sexually dimorphic in nature, appear to regulate hepatic levels of many microsomal steroid and drug metabolizing enzymes as well as steroid receptor levels (1,7,8).Since Higgins and Anderson originally reported (9) the technique of partial hepatectomy (PH) in rats, investigators have been studying the effect of hepatic resection and the remnant liver with the goal of identifying the mechanisms that regulate hepatic regeneration. During the last 10 yr, hormones have assumed a prominent role as factors related in some way to hepatic regeneration after PH.…”

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Sex Hormone-Related Functions in Regenerating Male Rat Liver

Francavilla¹,

Eagon²,

DiLeo³

et al. 1986

Gastroenterology

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Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration.Mammalian liver of both sexes is responsive to sex hormones. Liver is estrogen responsive in that it contains receptors for this hormone and responds by the synthesis of specific proteins (reviewed in Reference 1). Liver contains androgen receptors as well (2-5). In fact, the sexually dimorphic hepatic content of certain receptors and microsomal enzymes observed in male rats is maintained by testosterone (reviewed in References 1 and 6). Ultimate control over these sex differences in hepatic function resides in the pituitary gland. In particular, growth hormone secretion patterns, also sexually dimorphic in nature, appear to regulate hepatic levels of many microsomal steroid and drug metabolizing enzymes as well as steroid receptor levels (1,7,8).Since Higgins and Anderson originally reported (9) the technique of partial hepatectomy (PH) in rats, investigators have been studying the effect of hepatic resection and the remnant liver with the goal of identifying the mechanisms that regulate hepatic regeneration. During the last 10 yr, hormones have assumed a prominent role as factors related in some way to hepatic regeneration after PH. It has been suggested that hormonal agents such as insulin, glucagon, and epidermal growth factor may initiate the process of regeneration (10-17); however, other hormones such as parathyroid hormone (18) (23). These data demonstrated that the proliferative activity of the regenerating liver is concurrent with a significant increase in nuclear localization of hepatic ERs. However, this study did not examine possible increases in serum estradiol content that might account for the increased nuclear ER localization, nor was total hepatic content of ER examined. We have now extended the study to answer these questions, and in addition, to determin...

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Animal Cell Types, Liver Cells

Stacey

2000

Encyclopedia of Cell Technology

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Sex Steroid Induced Changes in Hepatic Enzymes

Cited by 313 publications

References 0 publications

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

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

Sex Hormone-Related Functions in Regenerating Male Rat Liver

Animal Cell Types, Liver Cells

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