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Altered steroid delta(4)-reductase activity in mammary tumor-bearing rats
Abstract:
The effect of mammary tumors on steroid delta(4)-reductase activity was investigated using in vitro and in vivo studies in three transplantable rat mammary tumors. Steroid delta(4)-5 alpha-reductase activity was measured spectrophotometrically and was significantly decreased in the host livers from R323OAC and MT/W9a-B but was increased in 7,12-dimethylbenz(a)anthracene-induced No. 14 tumor-bearing rats. There were no significant alterations of 5 beta-reductase activity in all animals investigated. In vivo studies using [14C]testosterone showed a similar pattern for saturation of the 4,5-double bond but that the more than doubled increase in 4,5-reduced metabolites observed in the in vivo studies in 7,12-dimethylbenz(a)anthracene-induced tumor-bearing rats cannot be explained by the increase observed in hepatic enzyme activity. Incubations with mammary tumor tissues showed that 7,12-dimethylbenz(a)anthracene-induced tumors have a very active delta(4)-5 alpha-reductase enzyme which accounts for the observed increases in in vivo results. The surgical removal of the tumor abolishes the impairment in delta(4)-reductase activity.
Insights
Mammary tumors alter steroid metabolism, decreasing hepatic delta(4)-5 alpha-reductase in some models but increasing it in others. Tumor removal reversed these effects, highlighting the tumor
Area of Science:
- Biochemistry
- Oncology
- Endocrinology
Background:
- Steroid hormone metabolism plays a crucial role in mammary gland function and cancer development.
- Alterations in steroid-metabolizing enzymes, such as delta(4)-reductases, are implicated in hormone-dependent cancers.
- Understanding the impact of mammary tumors on these enzymes is vital for comprehending tumor progression and potential therapeutic targets.
Purpose of the Study:
- To investigate the effects of transplantable mammary tumors on hepatic steroid delta(4)-reductase activity in rats.
- To differentiate the impact of various tumor types on steroid 5-alpha and 5-beta reductase activities.
- To elucidate the role of tumor tissue itself in altering steroid metabolism.
Main Methods:
- In vitro and in vivo studies were conducted using three transplantable rat mammary tumor models.
- Steroid delta(4)-5 alpha-reductase and 5 beta-reductase activities were measured spectrophotometrically.
- In vivo studies utilized [14C]testosterone to track metabolite formation, and tumor tissues were analyzed for enzyme activity.
Main Results:
- Hepatic steroid delta(4)-5 alpha-reductase activity was significantly decreased in R323OAC and MT/W9a-B tumor-bearing rats.
- Conversely, activity was increased in host livers of 7,12-dimethylbenz(a)anthracene-induced No. 14 tumor-bearing rats.
- Mammary tumor tissues, particularly 7,12-dimethylbenz(a)anthracene-induced tumors, exhibited high delta(4)-5 alpha-reductase activity, explaining in vivo findings. Surgical removal of tumors normalized enzyme activity.
Conclusions:
- Mammary tumors differentially affect hepatic steroid delta(4)-5 alpha-reductase activity depending on the tumor type.
- The high delta(4)-5 alpha-reductase activity within certain tumor tissues contributes significantly to observed metabolic alterations.
- Tumor-induced changes in steroid metabolism are reversible upon tumor removal, suggesting potential for therapeutic intervention.