Thursday, January 8, 2015

Hormones: the public announcement system of the brain

[Note: this post is part of the course materials for my upcoming online class, Hormones: from molecules to behavior, with APDT.]

There your dog is, minding his own business, when suddenly another dog attacks him. His brain now has a bunch of physical changes to coordinate very quickly to deal with the emergency: routing energy away from the non-essentials (digestion, reproduction, certain parts of the immune system) and to what his body needs right now (muscle speed and strength). How to get out this message of impending danger to all the body's organs quickly and efficiently?

Human societies sometimes solve this kind of problem with public announcement systems: a public broadcast in an airport to announce a flight change, a Facebook post to announce a change in relationship status, posters around a neighborhood about a lost dog. It’s not the most elegant of solutions. Having a direct connection to everyone you wanted to pass the message to would be better — the passengers on the flight with the changed departure time, your Facebook friends whom you think are particularly cute, the people who actually saw your lost dog running by. But in the absence of being able to call all these people directly, we just get the message out there and hope that the people who didn’t need it won’t be too annoyed, and the ones who do need it will respond appropriately.

Hormones are a similar low-elegance, high-efficiency answer to the same problem. In the case of your dog who is being attacked by another dog, his brain orders the release of stress hormones. Hormones are tiny molecules which can be carried by the bloodstream throughout the body. The message to each of the organs which see the hormones floating by is the same — get ready to deal with danger — but the response of each organ is different. In the case of stress hormones, the body alters its metabolism to prepare to use a lot of energy in fighting or running, the digestion slows, and the immune system is suppressed, among many other consequences.

Note that the brain is quite capable of sending direct messages without using hormones. The peripheral nervous system is a whole complicated network of nerves connecting the brain to individual parts of the body, so if a message needs to be sent directly and privately, it can be. But just as sending a hundred individual hand-addressed wedding invitations is annoying and time-consuming, sometimes the public broadcast approach is just easier.

I’ll go into more detail in future posts about how the brain causes hormones to be released, because it’s different for different systems. In short, the brain sends an executive order, and a hormone is released into the bloodstream. Just like pouring gallons of dye into a river on St. Patrick’s Day, there’s plenty to go around, even miles downstream, or, in this case, all the way to the most distant parts of the body.

The hormone message is carried through the bloodstream throughout the body, washing up against cells from every organ. This is where the story moves from macroscopic — things large enough to see with human eyes, like blood moving through vessels — to microscopic: molecules of hormone and individual cells. You’d be able to see a dog’s cell through a microscope, but not a molecule of hormone, so we’re entirely in the realm of our imagination here.

There is all kinds of stuff in a dog's (or a human's) blood. Not just molecules of cortisol. Molecules of other hormones — I’m personally particularly interested in the ones that are associated with behavior, like cortisol and oxytocin and vasopressin, but there are hormones that have nothing to do with behavior: insulin and glucagon for managing metabolism, lutenizing hormone (LH) and follicle-stimulating hormone (FSH) for reproduction, insulin-like growth factor for growth, and so on. And there are other things besides hormones — cells for the immune system (white blood cells), cells for carrying oxygen (red blood cells), antibodies, little proteins called cytokines released by individual cells to communicate with each other about the stuff cells care about (inflammation, infection, and so on), things that cells eat like sugar and free fatty acids — the list goes on and on. The bloodstream is a superhighway packed with traffic.

Cells need to be able to process all this stuff appropriately. In the case of hormones, they do it with receptors. A receptor is like a keyhole, tuned to exactly one key; the key is called a “ligand.” In the case of a receptor for cortisol (for which the technical name is glucocorticoid receptor), the ligand or key is cortisol. There is a very short list of molecules which will fit into this receptor like keys into a lock, and cortisol is on that list. Insulin might bump up against it as it is going about its way doing insulin things, but it won’t bind with the receptor: it won’t fit into the keyhole.

When cortisol bumps up against this receptor, on the other hand, it does bind. In technical terminology, it is the ligand for the receptor. The receptor is like a little robot which, when it gets its ligand of cortisol, suddenly activates, as if the key in the lock enables its switch to be flipped to “on.” It turns on and goes and does its preprogrammed job, interacting with many other little robots which are receiving other signals.

Somehow, in the chaos of a zillion little machines each doing a very simple job, some very complex biological processes get performed inside cells. It’s this complex interaction that explains why different kinds cells react differently to the same hormonal message. Remember that the muscles need to do one thing when they see cortisol and the intestines need to do something different: this is because their receptors are working in very different cell types, with different environments, and different cells may have more or fewer receptors. Of course there are some cells which don't much care about this particular message, and these cells don't have receptors for cortisol, allowing them to ignore it.

I’ll talk more about what glucocorticoid receptors do in a later post, but it's not all that important to understand this kind of minutia. The story at a high level is that the brain identifies a situation that requires action; it orders the release of a hormone to send a public broadcast message to the rest of the body; cells in the body which have specific receptors for this hormone get the message, and their receptors activate in response to binding to molecules of the hormone and perform the necessary work to respond to the message. The system is simple, but somehow allows for the bewildering complexity of the animal body.

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