What is it called when two of more hormones interact the combined effect on the target often exceeds the additive effect of each hormone separately?

• Endocrine Disrupting Chemicals
• The Hormones
  • Androgens
  • Corticoids
  • Estrogens
  • Progestins
  • Thyroid
• Actions
  • Docking: Receptor Binding
  • Delivery: Transport Proteins
  • Disposal: Metabolic Changes
  • Dynamics: Interactions
• Wildlife Effects
• Human Effects
• Sources
• Phytoestrogens
• Gathering Evidence
• What Does ED Mean?
• Endocrine System
  • Hormone Glands
  • Target Cells
  • Types of Hormones
  • Feedback Loops
• Glossary

1. Natural Hormone Production Varies
2. Transport Protein Levels Change
3. Potencies Differ
4. Dose Matters
5. Mixtures Might
6. References
   

Obviously, we are all different. Girls differ from boys. Infants differ from children who differ from adults. Individually, our looks, actions, preferences, and physical health vary.

Yet, we are also alike. We all rely on and share, with each other and most other vertebrate animals, similar genetic, hormone, and other signaling systems that control development, growth, and body maintenance and repair.

In this dichotomy, the physiological similarities are the reason why endocrine disrupters (EDs) can interfere with signaling systems in both people and animals. It’s the differences, guided by genetics and shaped by environment, that influence how EDs may ultimately interact with those systems and possibly affect an individual’s or species’ health and development.

Natural Hormone Production Varies

Natural hormone production varies with gender, age, and reproductive cycles. For instance, women produce more estrogen than men, estrogen is abundant during fetal development of both sexes, and post-menopausal women have very little estrogen. On the other hand, men produce more testosterone than women. Levels rage during puberty and decrease beginning in mid-life. In both sexes, but more commonly in women, thyroid hormone levels may also start decreasing in mid-life. Thus, endocrine disruptors may have different influences (mimicking or canceling out natural hormone effects) depending on existing hormone levels, which are dictated by age and gender.

Transport Protein Levels Change

Some hormone transport proteins in plasma are highly selective, transporting only steroid or only thyroid hormones. These highly selective transport proteins include sex hormone binding globulin (SHBG), which carries estradiol and testosterone; corticosteroid binding globulin (CBG), which carries glucocorticoids; and thyroid binding globulin (TBG) and transthyretin (TTR), both of which carry thyroid hormones. All vertebrates except birds have SHBG; only four-legged vertebrates have CBG; only some mammals, including humans, have TBG; and all vertebrates use TTR.

Other hormone transport proteins are relatively non-selective, transporting almost any lipophilic molecule that enters the bloodstream, including steroid and thyroid hormones, plant-derived flavonoids, retinoids (vitamin A), fatty acids, and antibiotics. Albumin is a relatively non-selective transport protein found in all vertebrates. As the most abundant plasma protein, albumin's blood concentration often far exceeds even the flavonoids that flood the bloodstream after fruits and vegetables are eaten. Although albumin is not strongly attracted to particular molecules, there is so much of it in the blood that it simply mops up and shuttles stray fat soluble molecules.

Potencies Differ

Natural hormones are more potent than any of the known synthetic and plant-derived hormone interlopers except drugs such as diethylstilbestrol (DES) and ethinyl estradiol, the drug in birth control pills. This means the foreign compounds are not as strong and higher doses may be needed to produce similar results as natural hormones. Although some wildlife are continually exposed during different life stages to very high levels of pollutants that can affect health and reproduction, it is still not clear whether exposure in these amounts occurs on a normal basis in humans.

Dose Matters

Phytoestrogens, the natural plant compounds capable of acting like estrogen hormones, may produce opposite effects depending upon dose. At very high amounts, some cause infertility in farm animals and wildlife. Lower doses seem to protect against breast and reproductive cancers in humans.

Mixtures Might

Combinations of certain synthetic and natural hormones may have additive, synergistic, or antagonistic effects (Bergeron et al. 1994, 1999; Thorpe et al. 2003). For instance, estrogens in a mix may become more potent by simply adding their individual effects together. Of particular concern is synergistic effects, where each estrogen may be harmless in similar concentrations by itself, but when mixed with other hormones, may produce more effect than predicted from its individual concentration. Synthetic estrogens may also antagonize each other's effects. That is, a weakly anti-estrogenic compound may cancel out a weakly estrogenic compound and produce no effect (Safe 1995).

References

• Bergeron JM, Crews D, and McLachlan JA. 1994. PCBs as environmental estrogens: Turtle sex determination as a biomarker of environmental contamination. Environmental Health Perspectives 102:780-781.
• Bergeron J, Willingham E, Osborn C, Rhen T, and Crews D. 1999. Developmental synergism of steroidal estrogens in sex determination. Environmental Health Perspectives 107:93-97.
• Jury H, Zacharewski T, and Hammond G. 2000. Interactions between human plasma sex hormone-binding globulin and xenobiotic ligands. J. Steroid Biochem. Mol. Biol. 75:167-176.
• Safe S. 1995. Environmental and dietary estrogens and human health. Environmental Health Perspectives 103:346-51.
• Thorpe K, Cummings R, Hutchinson T, Scholze M, Brighty G, Sumpter J, and Tyler C. 2003. Relative potencies and combination effects of steroidal estrogens in fish. Environmental Science and Technology 37:1142-1149.