Nutrition-endocrine interactions: Induction of reciprocal changes on the Δ4-5α-reduction of testosterone and the cytochrome P-450-dependent oxidation of estradiol dietary macronutrients in man

A. Kappas, Karl Anderson, A. H. Conney, E. J. Pantuck, J. Fishman, H. L. Bradlow

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Abstract

The in vivo biotransformations of drugs known to be metabolized by enzymes localized in the endoplasmic reticulum of liver can be greatly altered by diet in humans, as we have shown previously. Steroid hormones also are metabolized extensively by hepatic microsomal enzymes; therefore, we examined the possibility that testosterone and estradiol biotransformations, as assessed with radiolabeled tracer methods, could be influenced by dietary macronutrients. Normal males were fed a high-protein diet for 2 weeks, followed by a high-carbohydrate diet for an additional 2 weeks. The Δ4-5α-reduction of testosterone was considerably diminished, while the cytochrome P-450-dependent hydroxylation of estradiol at the C2 position was substantially enhanced during ingestion of the high-protein diet as compared with the high-carbohydrate diet. These results indicate that dietary macronutrients can significantly alter major metabolic pathways for testosterone and estradiol in man. The mechanism by which reciprocal changes in the Δ4-5α-reduction of testosterone and the cytochrome P-450-mediated oxidation of estradiol are produced by diet is not known. Similar changes in steroid Δ4-5α-reduction and cytochrome P-450-dependent chemical oxidations have been observed in circumstances in which the mixed-function oxidase system in liver is induced by agents such as phenobarbital, hexachlorobenzene, dioxin, and polyhalogenated biphenyls. Thus, the alterations in steroid hormone metabolism produced by dietary macronutrients in man mimic those that can be produced by drugs and environmental chemicals.

Original languageEnglish (US)
Pages (from-to)7646-7649
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume80
Issue number24 I
StatePublished - 1983
Externally publishedYes

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Cytochrome P-450 Enzyme System
Testosterone
Estradiol
Diet
Steroids
Biotransformation
Liver
Carbohydrates
Hormones
Hexachlorobenzene
Dioxins
Enzymes
Hydroxylation
Phenobarbital
Mixed Function Oxygenases
Metabolic Networks and Pathways
Endoplasmic Reticulum
Pharmaceutical Preparations
Proteins
Eating

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Nutrition-endocrine interactions: Induction of reciprocal changes on the Δ4-5α-reduction of testosterone and the cytochrome P-450-dependent oxidation of estradiol dietary macronutrients in man",
abstract = "The in vivo biotransformations of drugs known to be metabolized by enzymes localized in the endoplasmic reticulum of liver can be greatly altered by diet in humans, as we have shown previously. Steroid hormones also are metabolized extensively by hepatic microsomal enzymes; therefore, we examined the possibility that testosterone and estradiol biotransformations, as assessed with radiolabeled tracer methods, could be influenced by dietary macronutrients. Normal males were fed a high-protein diet for 2 weeks, followed by a high-carbohydrate diet for an additional 2 weeks. The Δ4-5α-reduction of testosterone was considerably diminished, while the cytochrome P-450-dependent hydroxylation of estradiol at the C2 position was substantially enhanced during ingestion of the high-protein diet as compared with the high-carbohydrate diet. These results indicate that dietary macronutrients can significantly alter major metabolic pathways for testosterone and estradiol in man. The mechanism by which reciprocal changes in the Δ4-5α-reduction of testosterone and the cytochrome P-450-mediated oxidation of estradiol are produced by diet is not known. Similar changes in steroid Δ4-5α-reduction and cytochrome P-450-dependent chemical oxidations have been observed in circumstances in which the mixed-function oxidase system in liver is induced by agents such as phenobarbital, hexachlorobenzene, dioxin, and polyhalogenated biphenyls. Thus, the alterations in steroid hormone metabolism produced by dietary macronutrients in man mimic those that can be produced by drugs and environmental chemicals.",
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T2 - Induction of reciprocal changes on the Δ4-5α-reduction of testosterone and the cytochrome P-450-dependent oxidation of estradiol dietary macronutrients in man

AU - Kappas, A.

AU - Anderson, Karl

AU - Conney, A. H.

AU - Pantuck, E. J.

AU - Fishman, J.

AU - Bradlow, H. L.

PY - 1983

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