Ghrelin: The Hunger and Lung Development Games

Writing about hormones is hard because anything I say will be incomplete by necessity.  I can only do so much research,  and will undoubtedly miss something.  More worryingly, there’s a lot nobody knows about our endocrine system, and all available overviews tend to overstate our level of certainty.  I will be ecstatic if in 10 years this entry turns out to be 60% true.  But we go to war with the facts we have, so:

Ghrelin is best known as… well if you’re me it’s “proof calories in/calories out is bullshit“, but it’s more commonly known as “the hunger hormone”.  The simple story is that cells in your stomach produce ghrelin in response to perceived space in the stomach (which may be one way gastic bypass surgery leads to decrease in food consumption: your stomach reports fullness almost immediately).  Your hypothalamus detects this and informs the brain, which interprets it as hunger, which should lead you to get food.

But nothing in the human body does just one thing.  For one, ghrelin is produced in other areas of the body.  Pancreas, intestines (sure, they have information about current digestion status), placenta (okay, the fetus needs a way to direct you to eat more), gonads, adrenal cortex, pituitary gland (well those are pretty general hormone production factories), kidneys (for…water…consumption?), and lungs (the hell)?

Ghrelin encourages storage of calories as fat, which could mean that eating more (to suppress ghrelin production)  would help you avoid fat gain or even allow fat loss.  But (one form of) ghrelin also triggers production of human growth hormone (in fact, that’s where the name comes from: Growth Hormone RELease INducing factor), which encourages burning fat and building muscle.  The important lesson here is that if someone every tells you “Do X lose weight because hormone Y does Z”, you should laugh at them, even if Y and Z are correct, because Y does 4 million other things, some of which are the opposite of Z.  Ghrelin’s presence in the lungs might be a mechanism to trigger HGH to trigger fetal lung development.  Or maybe not.  We don’t know.

Still in the realm of possibility, high ghrelin levels delay puberty and discourages ovulation.   This is a reasonable second job for the hunger hormone to have because transforming a zygote into a baby is an epic amount of work and you want to be well fed.   I seriously wonder about the effects on ghrelin on libido: given that humans have sex for both reproduction and social bonding,** I could see the effect going either way.

Ghrelin appears to have some mood effects.  When I first read this I assumed high ghrelin -> stress and depression, which would be a convenient way of explaining why I was so jumpy before my hypochlorhydria was treated.  Turns out, nope, ghrelin is an anti-depressant* , which may be one mechanism reinforcing anorexia.  But ghrelin also makes pleasant activities (eating, but also drugs, and it’s at least in the same brain neighborhood as sex) more rewarding.  It also has a bunch of effects on learning and memory and stress-based learning, mostly apparently positive.  This is the opposite of what I would have predicted, given how I and people I know act when hungry.

Lastly, ghrelin inhibits inflammation. To the point it may be useful as a treatment for autoimmune diseases like rheumatoid arthritis and multiple sclerosis.   This concerns and confuses me, possibly even more than growth hormone effects. Hunger and long term calorie deficits are associated with increased susceptibility to disease (as your body prioritizes short term goals over long term health), so maybe this is a happy accident?  But no, ghrelin promotes development of at least one kind of white blood cell.  The anti-inflammatory effect may explain why people often don’t want to eat while injured- your body lowers ghrelin levels to allow healing to occur, and the loss of appetite is a side effect.  But that’s highly speculative, the truth is we just don’t know.

For all that, ghrelin is one of the simplest hormones I’ve studied.  It has one obvious primary job, and several of its lessen effects seem at least related to that job.  We know where it is produced and a good chunk of how it achieves its (known) effects.  More fundamental hormones like progesterone, testosterone, or oxytocin are infinitely more complicated.  So this post is a little bit about the science of hunger, and a lot about how the human body is complicated and people with simple answers are liars.

*Should you be laughing at me right now?  Maybe.  The study in question shows actual behavior change, not a potential mechanism of behavior change (that’s this paper), but it is just one study.  Perhaps compromise on chuckling.

**What about pleasure, you ask?  Irrelevant from an evolutionary standpoint.  We feel pleasure because there is some actual useful purpose served.