The HPG Axis: Hormones of Male Reproduction

GnRH communicates with two specific endocrine cells within the anterior pituitary. These cells release hormones called gonadotropins. Ah - where have we heard that term before? Sounds familiar, right? Oh yes, I remember! Remember what 'GnRH' stands for? 'Gonadotropin-releasing hormone.' See, I told you that remembering its name would be important. The function of GnRH is right there in its name. It releases gonadotropin hormones from the anterior pituitary.

We'll learn more about gonadotropins later, but first let's talk about patterns of GnRH release. You see, GnRH isn't just released all at once, nor is it released all the time. It's actually released in pulses about every 60-90 minutes. Similarly, as GnRH is released in pulses, it creates similar pulses in the gonadotropins that it triggers. So, when GnRH is high, then gonadotropin release is also high, and when GnRH is low, gonadotropin release is low.

Both LH and FSH target specific cells within the testicles. If you're familiar with testicular anatomy, you may recall that the testes have two main divisions. There are the seminiferous tubules where sperm production takes place and then there are the interstitial spaces, or the spaces in between the tubules that are filled with cells and tissues. Now, don't disregard those spaces in between the seminiferous tubules quite yet. You see, even though they aren't making sperm like our tubules are, they are still really important.

The two main divisions of the testes

Say around 5% of a male's testosterone is actually converted to another androgen, a super-testosterone if you will, called DHT or dihydrotestosterone. DHT is what causes all that extra hair growth that males have and enlarges the male's external genitalia - you know, all those things that makes a man, well, a man, hence the term 'super-testosterone.' Now, just wait a second, guys - before you go and start trying to figure out how to get more DHT, I feel like I should warn you: excess DHT in males is also what causes male pattern baldness…just a thought. Sorry, DHT - but now, let's get back to our main androgen, testosterone!

The first job of testosterone is to travel into the seminiferous tubules. Once inside, testosterone and our other gonadotropin, FSH (you didn't forget about that one yet, did you?), both stimulate cells called nurse cells. These are the cells that regulate and promote sperm production.

The second job of testosterone brings us to something called negative feedback. Remember how we said that GnRH is released in pulses and not continuously? That's because it's subject to a process called negative feedback. All hormones in your body need to be regulated somehow. Negative feedback does just what it says. This is when a signal, usually a hormone, is sent from one or more cells and travels back to decrease or stop the release of another hormone.

In this case, when testosterone levels get too high, the body needs a way to decrease its production. So, high testosterone sends a signal from the testes back to the hypothalamus. Once in the hypothalamus, testosterone blocks the GnRH cells.

Now, let's take a moment to think about this. If testosterone blocks the production and release of GnRH, what then happens to LH? Remember, LH release is dependent on the levels of GnRH. So, if GnRH levels are decreased, then so are LH levels, and if LH levels decrease, then less LH is sent to the interstitial cells. If less LH is sent to the interstitial cells, then testosterone levels also decrease.

High testosterone levels can be reduced by the hypothalamus.

When FSH reaches the nurse cells, it triggers them to secrete two products. The first is androgen-binding protein, and it does just what it says - it binds androgens, including testosterone, so that they cannot leave the seminiferous tubules. That way, testosterone stays in the tubules to help sperm production. The second, inhibin, negatively feeds back to the pituitary, where it tells the endocrine cells releasing FSH to decrease FSH levels. This, in turn, decreases stimulation of the nurse cells so that sperm production can be controlled.

FSH stimulates nurse cells to secrete androgen-binding proteins.

Okay, before I let you go, let's go through a quick review. Boy hits puberty, boy's HPG axis kicks into gear, triggering the hypothalamus to produce GnRH. GnRH is released in pulses. It travels to the anterior pituitary, where it releases LH and FSH. LH and FSH both travel to the testes, where LH stimulates testosterone production in the interstitial cells and FSH stimulates sperm production and the release of androgen-binding protein and inhibin.

And don't forget that this whole signaling pathway has to be regulated somehow. I mean, we can't just have all these hormones being produced with no way to control them, right? That's where negative feedback comes in. In this system, testosterone feeds back to the hypothalamus to decrease GnRH, and inhibin feeds back to the pituitary to decrease FSH production.

And that's it - the control of puberty and male reproduction comes down to a handful of hormones that all work together. If you were to take just one of these hormones out, the whole signaling pathway would be messed up. Think about what would happen if LH was blocked. Testosterone wouldn't be produced and it couldn't aid in sperm production. Or, what about FSH? Then, androgen-binding protein wouldn't be released, and so the nurse cells would have no way of keeping testosterone in the tubules.

To be sure you understand the pathway, I would suggest going through each hormone and asking yourself what would happen to the rest of the pathway if each hormone was removed. Or, what about if each hormone was increased? Good luck!