Teaching
Case 6: Shape Matters

Session Objectives

Students will be able to:
  • Describe the structure of estradiol and the similarities it shares with many other estrogenic compounds
  • Explain how the estrogen receptor binds these compounds
  • Compare the two forms of the estrogen receptor and the compounds they bind best
In this class students consider the shapes of several estrogen mimics, and attempt to explain why cells respond to them as estrogens. Read this passage out loud, or ask for a volunteer to do so.

Estrogen is a confusing molecule. It makes male birds sing, it prevents heart disease, and it causes girls to enter puberty. But the multiple effects of estrogen are not its only mystery. Many different molecules, synthetic or produced by plants, fungi, or animals, can create an estrogenic response. What is it about these diverse molecules that allows them to mimic estrogen? What do they have in common? Based on these structural similarities and what you learned about the mechanisms of hormone reception, what can you tell about receptor systems from these molecules?

Divide the class into 5 groups, giving each two model sets and one of the chemicals above to build, while giving them these instructions

In groups you will use kits to construct a physical model of one of these molecules. If you don’t remember your organic chemistry and have trouble turning the drawing into a model, that’s okay, just ask for help.
When all the groups have finished making their molecule, we will compare them and try to find what they all have in common, and then try to infer the characteristics of the receptors from their similarities and differences.

18beta-estradiol
CAPTION: 17-β Estradiol is the primary female hormone (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine

DES
CAPTION: Diethylstilbestrol (DES) is a synthetic chemical that is strongly estrogenic and has been used in humans and livestock (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine


genistein
CAPTION: Genistein is an isoflavone found in high concentrations in soybeans and soy products like tofu and soymilk (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine


DDT
CAPTION: DDT was widely used as an insecticide, and is now used in parts of the world to prevent mosquito-borne malaria. (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine

ethinyl estradiol
CAPTION: Ethinyl Estradiol is the most common orally-active form of synthetic estrogen (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine

Lead and manage a discussion of these questions. Having an expert on ER binding helps! The students should answer the questions as the discussion proceeds.


  • What structure(s) do all these molecules have in common?
  • What can we deduce about the receptors from this?
  • What part(s) of these molecules have in common?
  • What can we deduce about the receptors from this?
  • Given what you learned about hormone reception last week, do you think these chemicals effect cells in the same ways, or might they all be estrogenic, but through different pathways?

Explain your thinking.

A short presentation on the structure and workings of the ER should take place here. The students should answer the questions as the discussion proceeds.

You will now be introduced to the structure of the Estrogen Receptors (ER) and how they work.

Case Assignment
  1. What are the two kinds of ER? How do they differ?
  2. What is the basic structure of the ER? What part binds the ligand?
  3. What does this tell you about what kinds of molecules in might bind?

References
  • Henley, DV, and Korach, KS. 2006. Endocrine-disrupting chemicals use distinct mechanisms of action to modulate endocrine system function. Endocrinology 147(6): S25-S32
  • Dodds, E.C., and Lawson, W. 1938. Molecular Structure in Relation to Oestrogenic activity. Compounds without a Phenathrene Nucleus. Proceedings of the Royal Society of London. Series B, Biological Sciences 125(839):222-32