Endocrine Disruption

Actions : Disposal :: Metabolic Changes
  1. CYPs: Making and Breaking
  2. Turning Bad to Worse
  3. Thyroid hormone production and disposal
  4. References

Call them the body’s production and clean up crew. Without them, we would have more trash – old messenger molecules and foreign, possibly dangerous, compounds - circulating through our bodies. With them, we can make essential steroid hormones and break down unneeded or harmful substances. Sometimes, though, these workers can turn the outsiders into more dangerous - even endocrine disrupting - substances.

CYPs: Making and Breaking

These specialized enzymes are called cytochrome P450s (CYPs (sips for short)). Like all enzymes, CYPs are specialized proteins that catalyze - jumpstart and increase the speed of - chemical reactions without being changed during the process.

The wide variety of CYPs help along the production and breakdown of all natural steroid hormones, such as the sex hormones estrogens, androgens, and progestins. During clean up, CYPs degrade the steroids they help create and take apart many other natural and synthetic fat derived (fat loving or lipophilic) compounds, including fatty acids, retinoids (vitamin A), bile acids, plant chemicals, and certain drugs and other foreign molecules.

CYPs, then, help maintain natural steroid hormone balance by producing and degrading the messengers as well as removing unwanted and possibly harmful substances.

To dispose of the unwanted substances, some CYP enzymes transform steroids and the lipophilic "foreigners” - those not produced in the body - into molecules that dissolve more easily in water and can be excreted in urine. These CYPs are always in the liver, kidney, and intestine at low levels. When foreign molecules in the blood enter liver cells, sensors in the cell switch on CYP production. The CYPs attack the foreigners and change their structure so they can be excreted.

Turning Bad to Worse

Unfortunately, these changes can make some molecules more dangerous. After being altered, the molecules can sometimes attach better to hormone transport proteins and receptors, so a compound that had no effect suddenly becomes an endocrine disrupter (ED). For example, some PCBs are transformed into strong competitors for thyroid transport proteins, displacing thyroid hormone and severely destabilizing thyroid hormone balance in the body.

Revved up CYP action due to foreign invaders can negatively affect hormone balance in another way. Some of the CYPs that break down foreign molecules are indiscriminant and also break down the body’s natural steroid hormones. This seems like a no win situation: either remove the foreign chemical and alter natural hormone balance or maintain hormone balance and keep the foreign chemical. However, the body’s feedback mechanisms that senses and regulates natural steroid hormone levels usually compensates by making more hormone to stabilize the body’s hormone levels.

Thyroid hormone production and disposal

Thyroid hormones - mainly thyroxine and triiodothyronine (T3) - regulate metabolism and are essential for tissue growth, development, and function. The hormones are made in the thyroid gland during a complex process that involves adding iodine atoms to the amino acid tyrosine. Pairs of linked, iodinated tyrosines are clipped from a long chain of amino acids to form thyroxine. The thyroid gland secretes thyroxine into the bloodstream where thyroid transport proteins carry it to target cells. In the target cells, deiodinase enzymes remove an iodine atom from thyroxine converting it to the active hormone triiodothyronine (T3).

To turn off the signal, deiodinase enzymes strip iodine molecules from the tyrosines. Enzymes in the liver and kidney further modify the inactive hormones by adding sulfate and sugar groups to make them more water soluble and easily excreted in the bile.

A delicate balance of thyroid hormones ensures health: producing too much (hyperthyroidism) or too little (hypothyroidism) shifts the status quo causing problems such as weight loss and irritability (hyperthyroidism) or sudden weight gain and sluggishness (hypothyroidism).

Foods, EDs, and other factors can affect this balance. For example, eating extremely large amounts of certain vegetables and fruits can cause goiter, an over-sized thyroid gland. These foods, including cabbage, Brussels sprouts, cauliflower, turnips, sweet potatoes, sorghum, apricots, cherries, and almonds, contain high concentrations of sugar-like molecules called cyanogenic glucosides and thioglucosides. Digestion converts these substances into cyanide-containing molecules that block iodine from being added to tyrosine. The net effect is severely decreased thyroid hormone levels. Eventually, the thyroid gland enlarges from trying to produce enough thyroid hormone. Eating normal amounts of these cyanide-generating foods helps prevent many cancers.

Some PCBs and their breakdown products deliver a double-whammy to thyroid hormone balance. These chemicals boost the number of sugar-adding enzymes in the liver, which can increase hormone excretion, and also out compete natural thyroid hormone for binding to transport proteins leaving the hormone without an escort. In essence, sugar is added to the free-floating thyroid hormone, and it is excreted. Thyroid hormone levels then drop, and the thyroid gland can balloon into a goiter. Enlarged thyroid glands have been observed in wildlife, such as herring gulls and rainbow trout living in the Great Lakes region (Leatherland and Sonstegard 1980; Moccia et al. 1986).

  • Leatherland JF and Sonstegard RA. 1980. Seasonal changes in thyroid hyperplasia, serum thyroid hormone and lipid concentrations, and pituitary gland structure in Lake Ontario coho salmon, Onchorhynchus kisutch Walbaum and a comparison with coho salmon from Lakes Michigan and Erie. J Fish Biol 16:539-562.
  • Moccia RD, Fox GA, and Britton A. 1986. A quantitative assessment of thyroid histopathology of herring gulls (Larus argentaltus) from the Great Lakes and a hypothesis on the causal role of environmental contaminants. J Wildlife Diseases 22:60-70.