How does Progesterone create a Dopaminergic Response?

Well, this is strange. How did a hormone and a neurotransmitter get into the same sentence? After all, one is in the brain and one is in the body? Heck, when we study anatomy and physiology, we learn about the neurotransmitters (like dopamine, serotonin and acetylcholine) in our neurology classes. After we go through all of that, we close that chapter and move on to the next chapter. The next chapter could very well be hormones, but you only learnt about them once you have closed the chapter on neurotransmitters.
Now we know neurotransmitters are not just limited to the neurons. For example, the ‘neurotransmitter’ serotonin is mostly found in your bowels. In fact, 95% of the serotonin in your body is found in your bowels and only 5% is found in your brain. This is remarkable because for decades, serotonin was a brain chemical targeted by herbs such as Hypericum and drugs like Prozac.

We now know that neurotransmitters like dopamine and progesterone interact. As we will see later the link between these two chemicals are closely related.

The Invitro History of the Progesterone/Dopamine link

The first lines of evidence that progesterone activates dopamine were completed in an in-vitro setting (i.e., in test tubes). Most lines of evidence start with in-vitro testing because there is no harm to humans and the process is relatively quick and easy to perform. In 1984 a paper was released in “Neuroendocrinology”, which is a paper dedicated to the effects of hormones on the brain. The researchers gave differing doses of progesterone to rats, sacrificed the rats and then measured the release of dopamine from their brains. They found that the dopamine release from the corpus striatum was enhanced when the rats were given progesterone. So, the link was established (in rats at least).

The role of Progesterone in the Body

In women with menstrual cycles, progesterone naturally increases and decreases over their 28 day cycle. Put simply, progesterone levels stay relatively low until you ovulate. Once you ovulate, the egg released starts making loads of progesterone to ready the endometrium to accept the fertilised egg so a baby can grow! If the egg is not fertilised, the egg simply dies, stops producing progesterone and the endometrium falls away. Once this endometrium falls away the woman gets her period.

Progesterone in the Human Brain

There is strong evidence that progesterone plays an important role in the human female brain. Progesterone receptors are highly expressed in women’s brains that are involved in emotion, such as the hippocampus and the amygdala. Thus, it makes sense that if there are hormonal receptors there, there is a function of that chemical on that part of the brain and in this case, affects moods via the dopanergic system.

The role of Progesterone on Dopamine

While oestrogen can also regulate dopamine release, progesterone also plays a major role. Progesterone can affect dopamine levels via numerous mechanisms including affecting the release, turnover, receptors and transporters. Progesterone has been found to stimulate dopamine release, while oestrogen has been found to inhibit dopamine actions. So clinically, these opposing actions help to regulate dopamine release, if the woman’s hormones are in check. If the hormones become out of balance, dopamine levels, along with other neurotransmitters can change, leading to mood changes that affect some women during their menstrual cycle.

Detecting Dopamine levels in the Brain

The only direct way of measuring dopamine in the brain is using advanced techniques such as positron emission tomography or a single-photon emission computed tomography. Ok, these are not practical in the real world. However, if you do suspect you have dopamine levels that are out of whack, clinicians have realised that the spontaneous eye blink rate (EBR) is directly related to dopamine levels in women. The more blinks, the more dopamine you have floating around in your brain. In conditions such as Parkinson’s disease, where there is diminished dopamine, blinking is greatly reduced. In hyper-dopamine conditions, such as schizophrenia, spontaneous blinking is accelerated. Of course, blinking is also under conscious control so measuring your blinking yourself is flawed because you can make a conscious decision to blink or not to blink.

The take home message

No longer can we think of progesterone as a sex hormone only, because it, like oestrogen and testosterone for that matter play a significant role in the brain via the modulation of numerous neurotransmitters such as dopamine. As there are many parts of the brain, each part of the brain can be affected differently by the same hormone.
As progesterone and oestrogen fluctuate over 28 days of a menstruating cycle, this leads to quite radical changes in dopamine and other neurotransmitter levels in the brain. The result is altered moods that potentially can be quite devastating to women.
Spontaneous blinking may be one way to determine whether dopamine levels may be altered, but this needs to be assessed by a qualified health care professional to take out the conscious effects we have on our blinking rates.


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