Diindolylmethane Promotes Healthy Estrogen Metabolism

 

"Safer Estrogen with Phytonutrition"

Zeligs MA

Townsend Letter for Doctors and Patients (1999) April; 189:83-88.

Phytonutrition encompasses the dietary use of micronutrients found in plants. Adequate intake of specific phytochemicals improves health by regulating hormone metabolism and cell behavior. Cruciferous vegetables such as cabbage, cauliflower, and broccoli, posses unique phytochemical constituents able to modify the metabolism of estrogen.

The most important of these phytochemicals with regard to estrogen metabolism is the dietary indole, diindolylmethane. Supplemental use of diindolylmethane provides the basis for nutritional support to enhance the beneficial action and safety of estrogen. An optimal estrogen metabolism has implications for cancer prevention and successful aging in both women and men.

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"Diet and estrogen status: the cruciferous connection"

Zeligs MA.

J of Medicinal Food (1998) Nov 2; 1: 67-82.

Cruciferous vegetables, such as cabbage, cauliflower, and broccoli, have been cultivated since antiquity as medicinal plants. Once ingested, the Cruciferae possess unique phytochemical constituents able to modify the activity of cellular enzymes responsible for carcinogen clearance and estrogen metabolism.

The most active of these phytochemicals with regard to estrogen is the dietary indole, Diindolylmethane (DIM). Understanding the dietary influences of cruciferous phytochemicals on estrogen status provides a basis for nutritional approaches to estrogen-related concerns which accompany aging in women and men.



"Ah receptor binding properties of indole carbinols and induction of hepatic estradiol hydroxylation"

Jellinck PH, Forkert PG, Riddick DS, Okey AB, Michnovicz JJ, Bradlow HL.

Biochem Pharmacol 1993 Mar 9; 45(5):1129-36.

The effect of route of administration on the ability of indole-3-carbinol (13C), an anticarcinogen present in cruciferous vegetables, to induce estradiol 2-hydroxylase (EH) in female rat liver microsomes was investigated and compared to that of its main gastric conversion product, 3,3'-diindolylmethane (DIM). This dimer was more potent than 13C after either oral or intraperitoneal administration and was also a better in vitro inhibitor of EH in control and 13C-induced hepatic microsomes. The induction of both CYP1A1 and 1A2 in about equal amounts by 13C and DIM as well as of CYP2B1/2 was demonstrated using monoclonal antibodies. DIM, isosafrole, beta-naphthoflavone, 3-methylcholanthrene and naringenin added in vitro inhibited EH strongly in induced microsomes but gestodene was a better inhibitor of estrogen 2-hydroxylation in liver microsomes from untreated female rats.

The binding affinities of 13C and DIM to the Ah receptor were compared to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by competition studies, and the IC50 values were shown to be 2.0 x 10(-9) M, 5.0 x 10(-5) M and 2.3 x 10(-3) M for TCDD, DIM and 13C, respectively. The ability of 13C or DIM to cause in vitro transformation of the Ah receptor to a form able to bind to the dioxin-responsive element-3 (DRE3) was compared to that of TCDD and shown to parallel their abilities to compete for binding of [3H]TCDD to the Ah receptor.

These experiments confirm and extend the proposals that dietary indoles induce specific cytochrome P450s in rat liver by a mechanism possibly involving the Ah receptor. The induced monooxygenases, in turn, increase the synthesis of 2-hydroxylated estrogens in the competing pathways of 2- and 16 alpha-hydroxylation which decreases the levels of 16 alpha-hydroxyestrone able to form stable covalent adducts with proteins including the estrogen receptor. Such steroid-protein interaction has been correlated with mammary carcinogenesis.



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