Induction of monooxygenases and growth in rat liver by progesterone

Ochs, H R; Düsterberg, B.; Schulte‐Hermann, Rolf

doi:10.1007/bf00316323

Cited by 15 publications

(9 citation statements)

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“…The effects of estrogens and progesterone on hepatic P450 expression have been examined in animals (Dean and Stock, 1975;Waxman et al, 1985;Dannan et al, 1986;Ochs et al, 1986;Waxman and Holloway, 2009). In rats, estradiol is known to enhance expression of female-predominant CYP2C7 and female-specific CYP3A9 (Bandiera and Dworschak, 1992;Wang and Strobel, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…In rats, estradiol is known to enhance expression of female-predominant CYP2C7 and female-specific CYP3A9 (Bandiera and Dworschak, 1992;Wang and Strobel, 1997). In contrast, progesterone alters the rate of drug metabolism in a substrate-specific manner, suggesting P450 isoform-specific effects of progesterone on drug metabolism (Dean and Stock, 1975;Ochs et al, 1986). Extrapolation of these results to humans, however, is difficult in part due to significant divergence in hepatic drug-metabolizing enzyme genes and apparent differences in regulation of drug-metabolizing enzymes expression between humans and rodents.…”

Section: Introductionmentioning

confidence: 99%

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Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone

2012

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone

2012

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“…In one of the earliest papers on this subject, Goldberg (1966) noted that in rats fed high protein diets, there was evidence of liver enlargement without corresponding changes in levels of liver-specific enzymes (other than enzymes involved in the urea cycle, Argyris 1971). Other physiological events reported to induce liver enlargement in rats include hormones induced during pregnancy (Gershbein 1958, Ochs et al 1986, White and Gershbein 1987 and inflammation (Kunz et al 1966). In these circumstances, liver enlargement was not associated with pathological changes, and the liver weights returned to control levels when the conditions causing the liver enlargement were terminated.…”

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confidence: 99%

Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one-and tworing species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/ chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. Introduction Scope and purpose of the documentThe present document summarizes information on the physical/ chemical properties and toxicological hazards of hydrocarbon solvents and provides examples of the ways in which the information on hazard characterization can be used for hazard classification and to set occupational exposure limits. Many of the toxicological studies were published separately, but the results are summarized herein and referenced in the appendices.Hydrocarbon solvents are liquid hydrocarbon fractions that are primarily produced by the distillation of petroleum feed stocks or their synthetic analogs (e.g., Fischer-Tropsch derived materials), sometimes followed by additional processing steps such as solvent extraction, hydrodesulfurization, or hydrogenation. 1 Most hydrocarbon solvents are complex substances with variable compositions and are best described as UVCB 2 (unknown and variable composition) substances, but some are single constituent (mono-constituent) substances. The complex and variable nature of these solvents is the consequence of their manufacturing processes. In short, most hydroca...

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“…The liver is not a target tissue for progestins; in fact, while it is generally accepted that this tissue does not possess intracellular receptors for progesterone, some authors, nevertheless, have described a number of hepatic effects of PR (Feuer et al 1986;Ochs et al 1986a;Martelli et al 1998). Furthermore, the existence of a specific binding site for PR (PR binding site; PBS) in rat liver microsomes has been reported (Yamada and Miyaji 1982;Yamada et al 1990).…”

Section: Introductionmentioning

confidence: 92%

Steroid hormone progesterone induces cell proliferation and abnormal mitotic processes in rat liver

et al. 2001

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The aim of this study was to evaluate the acute hepatic effects exerted by the steroid hormone progesterone (PR) in the rat. Although the liver is not a target tissue for this hormone, a number of hepatic actions of PR have been described, and, furthermore, a specific binding site for PR (PBS) exists in rat liver microsomes. Immature male rats were treated intraperitoneally with 60 mg/kg PR per day for 1, 5 or 10 days, and different parameters were evaluated in order to detect possible alterations in liver cells. Morphological study of the livers did not present images of cytotoxicity in any group of animals. The presence of a clear hyperplasia of smooth endoplasmic reticulum (SER) was noteworthy, mainly seen in perilobular hepatocytes. Despite this SER increase, the levels of cytochrome P450 (Cyt P450) significantly decreased after 10 days of PR administration. Similarly, the concentration of PBS was significantly decreased after 10 days of treatment with PR. On the other hand, these studies revealed a clear increase of mitotic activity and Ki-67 labelling index in the livers of animals treated with PR; furthermore, livers of PR-treated animals showed an increased percentage of binucleate hepatocytes. Flow cytometry analysis showed that although ploidy status of liver cells was not modified in any case the percentage of diploid nuclei in S-phase decreased during treatment with PR. The most relevant finding was the presence of abnormal mitosis and c-mitosis in livers from animals from all PR-treated groups. This study demonstrates that PR (a) does not induce cytotoxicity although it can induce cell proliferation and spindle disturbances in liver cells, (b) may also modulate the drug-metabolizing liver enzyme function, and (c) downregulates the expression of its own microsomal specific binding site.

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Induction of monooxygenases and growth in rat liver by progesterone

Cited by 15 publications

References 15 publications

Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone

Isoform-Specific Regulation of Cytochromes P450 Expression by Estradiol and Progesterone

Characterization of the toxicological hazards of hydrocarbon solvents

Steroid hormone progesterone induces cell proliferation and abnormal mitotic processes in rat liver

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