How do estrogens work?

If you have an inquiring mind you may wonder how it is that estrogens, or any other hormone or drug for that matter, actually do the things they do in the body. I find this aspect of medicine fascinating and admire the dedicated researchers who spend hours trying to elucidate the biochemical processes that make our bodies work.

Estrogen and our other sex hormones are derived from the cholesterol molecule – which chemically consists of 4 carbon-based hexagonal rings that are joined together like hula hoops. The body’s enzymes then add and remove other molecules like nitrogen and hydrogen to convert it into a unique hormone.  Cholesterol exists in essentially all life forms and plays many roles.  It is the main constituent of cell walls and membranes in animals and plants.  That is why most of the commercial estrogen compounds can be made from plant products.

Our ovaries convert compounds made from cholesterol into estrogen and release it into the circulatory system. There it floats around in the blood along with millions of other agents – ranging from simple sodium chloride (salt) molecules to complex proteins.  All of these elements flow into our tiniest vessels, the capillaries, where they come in contact with the billions of cells in our body.

Each of our cells is coated with dozens of receptors.  These receptors have specific properties that attract only certain molecules and proteins whose geometric conformation is a match – like a lock and key. Once an estrogen molecule inserts itself into its receptor the show begins.  Depending on the type of cell being activated, various physiologic events can be triggered.  In some cases, the estrogen-receptor interaction triggers the cell to release certain chemicals that can have some specific effects – such as those that fight inflammation.  In other cases the interaction sets off a cascade of chemical events inside that cell that ultimately affect the DNA – turning on or off genes that make proteins.

This is where things get very complex and you need a PhD in biochemistry to truly understand the next steps. So I will take some poetic license and try to describe things in simplified terms. Let’s start with the changes that occur with puberty.  When this time arrives, estrogen, progesterone and testosterone levels go up dramatically.  Estrogen and progesterone interact with the ducts and glandular cells in the breast and stimulate them to grow and mature.  Thus the breasts enlarge and become capable of producing milk.  Testosterone hooks up with receptors on dormant hair follicles and stimulates hair growth under the arms and in the pubic area.

Estrogen and progesterone play an important role in maintaining strong bones. They do this by interacting with the receptors on specific cells that are responsible for keeping the bone building and breakdown process in balance. At the time of menopause, when the hormone levels go down, the bone breakdown cells are unleashed and there is a net loss of bone mass and this is what leads to bone thinning and osteoporosis.

We are learning a great deal about the role estrogen plays in our cardiovascular system. There are a number of things that estrogen does that protects women from heart disease. The inside of our arteries are coated with estrogen receptors.  It has been shown that circulating estrogen stimulates the release of a chemical called nitrous oxide.  This agent can quickly dilate the artery which allows more blood flow.  It has been shown that high levels of nitrous oxide improve blood pressure and also protect the lining of our arteries from damage.  This decreases the risk of plaque buildup – which is the gunk that can block our arteries and lead to heart attacks and strokes.

It has also long been known that women tend to have higher levels of HDL, the “good” cholesterol, and lower levels of “bad” cholesterol, the LDL. This cholesterol pattern is associated with a decreased risk of developing hardening of the arteries. Estrogen is responsible for much of this by promoting the liver to remove the bad types of cholesterol, as well as stimulating the production of the good types.

More and more research papers are being published on the important role estrogen plays in our bodies and how it accomplishes this. As a woman, these findings impress me that we need to be aware of these estrogen-based functions so that we better understand what can happen to us when estrogen disappears at menopause.