ESTROGEN | Phase 2
Once produced, estrogen moves through the blood and exerts its influence in the body by binding to estrogen receptors (ERs). ERs are important since they are also known to bind to DNA and control gene expression.
There are two types of estrogen receptors encoded by two separate genes:
ER alpha (ESR1) - found in the highest concentration in the endometrium, ovaries, and hypothalamus (in the brain). ESR1 increases the action of the attached estrogen
ER beta (ESR2) - found in highest concentration in the ovaries, kidneys, brain, bone, heart, lungs, intestinal mucosa and endothelial cells. ESR2 weakens the action of the attached estrogen.
After phase I conversion, estrogen metabolites pass through phase II detoxification where they are neutralized and prepared for excretion via urine and bile.
The 4 main estrogen detoxification enzymes are:
COMT (Methylation): the COMT enzyme turns 2OH and 4OH into the neutral compounds, 2-meOH, and 4-meOH respectively via a process called methylation. Methylation is a major mechanism for preventing the potentially harmful effects of estrogen in the body.
GSTs (Glutathione Transferases): the GSTs are vital phase II detoxification enzymes responsible for providing protection against toxins by neutralising free radicals in the body with the help of the powerful antioxidant, glutathione.
SULT (Sulphation): estrogen metabolites are also deactivated via sulphotransferase enzymes
UGT (Glucuronidation): the UGT enzymes render estrogen more water-soluble and ready for excretion via the bile to the small intestine
Knowing which of your phase II pathways might be sluggish or in need of extra support is important to prevent your exposure to the toxic estrogen metabolites that have been linked to estrogen-positive breast cancer.