Teachable moment in classrooms:

  1. endocrine system chapter – concept of hormones interacting with receptors in order to change cell behavior
  2. brain chapter – anatomy and function of hypothalamus
  3. metabolism chapter – role of hypothalamus in thermoregulation

The news item:  Recently the following news report appeared online:

FDA approves nonhormonadrug to treat hot flashes and night sweats

The new drug, fezolinetant, could be a “game-changer” for women who don’t want to take hormone replacement therapy or who have been treated for hormone-sensitive cancers.

The article states that a new pharmaceutical called Veozah was approved for use to combat hot flashes in women undergoing menopause. The article states that while estrogen supplementation is the most effective treatment for hot flashes, breast cancer survivors can not take estrogen, and for those women now there is an alternative; Veozah was effective in 48% of the patients. The article also states that Veozah blocks a receptor in the brain.

So, Why Do I Care??  There are 4 million breast cancer survivors who can now take advantage of this treatment. Hot flashes can lower one’s quality of life to the degree that holding down a job, or socializing is difficult.

Plain English, Please!!!  First, let’s talk about what are “hot flashes”. Hot flash is a brief feeling of being overheated even when the environment has a normal temperature.  During hot flashes the body creates sweating and vasodilation, the normal responses to true overheating. Because there is no real overheating of the body, hot flashes are considered instances of abnormal temperature regulation. Commonly, hot flashes happen in menopause when estrogen levels decrease in women.

Second, let’s talk about how our bodies normally respond to overheating.  Our core body temperature is maintained at 100 oF by a biological thermostat. Picture the thermostat in our homes: when the house is over-heating, the temperature sensors in that plastic box on the wall detect it, a control center in the box turns on the air conditioning unit. In our body the temperature sensors (thermoreceptors) and the control center are located in the hypothalamus, and our air-conditioning is sweating and vasodilation in the skin. The hypothalamus starts to act only when core body temperature rises at least 0.5 oF. The temperature sensitivity of the hypothalamus can be adjusted by small molecules in the blood; for example, during a fever interleukins and bacterial products can instruct the hypothalamus to tolerate higher than normal core body temperature.

Third, let’s talk about how Veozah acts. During hot flashes a small peptide called neurokinin 3 increases the sensitivity of the hypothalamus in a way that it starts to react to very small rises in the core body temperature. The sensitized hypothalamus starts the sweating and vasodilation responses when there is no truly significant rise in core body temperature. Neurokinin 3, just like any water-soluble hormone, acts on neurons through cell surface receptors. The hormone binds to a receptor, like a baseball is caught in baseball mitt.  Then the receptor instructs the cell about how to change cellular action. The molecules in the drug Veozah fill the baseball mitt (stick to the receptor) and prevent the catching of the baseball (binding of neurokinin 3 to the receptor). When that happens the neurons of the hypothalamus are not sensitized, they retain their tolerance of small temperature rises, and do not start a hot flash reaction.