• Describe how hormones find their target cells
• Explain the difference between classical and fast-signaling mechanisms for estrogen action on cells
• Define explain why estrogen levels might not be high in and individual experiencing environmental feminization
  

He sat in the waiting room, 50 years old, in a dark suit with a pale blue tie. His gray hair was parted on one side, combed back in the feathered fashion of the early 1980’s, thicker than on the head of many men his age. A little overweight, he shifted in the hard fabric chair, and tried to focus his mind on the silly magazine article in front of him. He was nervous, or perhaps embarrassed was a more appropriate term. When he brought his complaints to his own physician it was one thing, but to speak of such personal things to a group of strangers would be quite uncomfortable. As a mortician he was used to uncomfortable conversations, but the ones he had learned to navigate had to do with death and grief, not libido, or an overly thin beard. Over the last decade, in addition to a declining sex drive and the need to shave less often, his testicles had gotten smaller, and he seemed to be growing breasts. It had been most obvious recently, just before and since his bypass surgery, but it was gradual, so it was hard to tell if it was really happening, and if it was just growing old. His wife’s growing distaste for him was part of the reason he decided to bring it up with the doctor. How could anyone consider a man who’s loins had produced 7 children lacking in virility? He hadn’t really expected his physician, who he’d been seeing for 30 years almost, to take him seriously. Then he had been sent to these specialists, and his discomfort turned to humiliation.

In 1982 a man who worked as a mortician was referred to the endocrinologists at Massachusetts General Hospital. His physical exam showed bilateral gynecomastia (enlarged and tender breasts on both sides), and testicles less than half of normal size. His lab results showed very low levels of both testosterone and estrogen, but otherwise normal levels of other hormones and iron, and no liver malfunctions. Also normal were x-rays and CT scans of his pituitary and hypothalamus.
He had no prior history of endocrine problems, but disclosed that he conducted embalmings, and did not use gloves as recommended when applying embalming cream to bodies.

He was admitted for further tests, and then a treatment of weekly intramuscular testosterone enanthate injections was prescribed. This was partially effective. Three years later, he had remarried experiencing fertility problems. His testicle size and sperm count had increased to normal levels, and he reported that he had stopped embalming over a year before. Testosterone injections were discontinued and in a month his wife had conceived.

Lead and manage this discussion. Compare this case to the one in Case of the Cross-Dressing Carp. Would it be possible for that young man to have shown his symptoms and not had high estrogen levels?

Discussion Questions:

What do you think was causing his symptoms? What evidence can you cite to back your claims?

If something was in his body and circulating, it caused problems in only some tissues. This is true of all hormones--they circulate throughout the body but only affect some tissues? Why would that happen, how could it happen? Why do some cells receive the signal and respond, while others do not?

1. What determines if cells respond to a signal or not?
2. Describe nuclear receptors and how they work.
3. Describe the fast-signaling pathway and how it works.
4. What are some important differences between the two mechanisms?

• Henley, DV, Korach, KS. 2006. Endocrine-disrupting chemicals use distinct mechanisms of action to modulate endocrine system function. Endocrinology 147(6):S25-S32
• Moore, JT, et al. 2006. The Nuclear Receptor Superfamily and Drug Discovery. ChemMedChem 1:504-23
• Wehling, M, and Losel, R. 2006. Non-genomic steroid hormone effects: Membrane or intracellular receptors? Journal of Steroid Biochemistry and Molecular Biology 102:180-3
• Evans, R. 2005. The nuclear receptor superfamily: a Rosetta Stone for physiology. Molecular Endocrinology 19:1429-38
• Losel, R. et al. 2003. Nongenomic steroid action, controversies, questions, and answers. Physiological Review 83:965-1016.
• Finkelstein, Joel, et al. 1988. The Mortician’s Mystery: gynecomastia and reversible hypogonadotropic hypogonadism in an embalmer. New England Journal of Medicine. 318:961-5.