Heather has taught reproductive biology and has researched neuro, repro and endocrinology. She has a PhD in Zoology/Biology.
Female HPG Axis
Here we are, girls - the age of puberty! Okay, now everybody get in line. Who's first? Are you ready to leave your childhood behind and enter the world of womanhood? It may be a bit awkward at first, but don't worry, you'll get used to it. Now remember, don't squeeze your pimples; you'll just leave scars. Don't wear too much makeup, and don't forget about PMS - try not to let the mood changes get the best of you!
Do you ever wonder where all those changes you go through in puberty come from? Well, you see, you have this pathway in your body called the HPG axis. That stands for hypothalamic-pituitary-gonadal axis. It starts in your brain, where the hypothalamus and the pituitary are located, and it allows your brain to communicate with your ovaries using molecules called hormones.
Hormones are like messengers. They carry signals or instructions from one structure to the next via the body's bloodstream. And they usually work with other hormones in the body to pass along those instructions. And puberty, well, that's the time of life when the HPG axis gets activated. You see, before that, the pathway is there, but it hasn't really been turned on yet. Once you hit puberty, though, your HPG axis is now active and ready to go.
Go where, you ask? Well, it helps propel you from the realm of childhood through puberty and into womanhood! Basically, it prepares your body for reproduction. Without an HPG axis, you wouldn't be able to produce gametes, or eggs, that are necessary for reproduction.
So, how does it all work? Well, let's start at the top, the head honcho of the group - that's the brain! Within your brain, you have an area called the hypothalamus. It's an area of your brain important for many things, including regulating reproduction. The hypothalamus is located at the bottom, middle portion of your brain, directly above another structure known as the pituitary. The pituitary is another portion of the brain important in hormone regulation and numerous signal pathways within the body.
The two main functions of the hypothalamus (with regards to reproduction) both involve the same neurohormone (that's just another way of saying a hormone that's made in the brain). That hormone is called gonadotropin-releasing hormone, or GnRH for short. GnRH from the hypothalamus is responsible for both the initiation of puberty and for the regulation of hormones involved in female reproduction.
Now, remember how we said hormones don't usually work alone? Well, GnRH is just the first hormone in a series in the HPG pathway. You see, GnRH is made in neurons in the hypothalamus, and once produced, GnRH is released into a series of capillaries in the brain called the hypophyseal-portal system. This is a network of blood vessels that connects the hypothalamus to the anterior pituitary, allowing them to communicate with each other.
Once GnRH gets to the pituitary, it diffuses out of the blood and into endocrine cells located in the anterior pituitary. The anterior pituitary is the front half of the pituitary, and it contains a number of endocrine cells. Endocrine cells secrete hormones into the body's bloodstream. These hormones can travel all over the body, but we're just going to focus on those that travel to the ovaries.
GnRH communicates with endocrine cells that release hormones called gonadotropins. Okay, let's take a moment to think back to what GnRH stands for: gonadotropin-releasing hormone, right? The function of GnRH is right there in its name. It releases gonadotropin hormones from the anterior pituitary.
So, now that we understand what GnRH does, let's look at how. Importantly, GnRH levels fluctuate as the female progresses through her monthly ovarian and menstrual cycles. That's because the gonadotropins - called LH and FSH - are only needed during certain parts of the ovarian cycle (that's the cycle that ovaries go through). So, as GnRH levels change, so do the levels of gonadotropins that it triggers. When GnRH is high, then gonadotropin release is high, and when GnRH is low, gonadotropin release is also low.
So, what are these gonadotropins I keep talking about? There are two of them, actually - luteinizing hormone (or LH for short) and follicle-stimulating hormone (or FSH for short). Each of these hormones has a specific role in female reproduction.
When GnRH diffuses out of the capillary system and into the anterior pituitary, it causes both LH and FSH to be released into the body's bloodstream. Both of these hormones travel down to the ovaries, where they control different parts of the ovarian cycle. The ovarian cycle is just a series of changes in the ovaries that occur on a monthly cycle basis. This cycle is split into two halves, the follicular phase and the luteal phase, with ovulation (which is the release of a mature egg) being right in the middle of the two.
Let's start with FSH first. FSH has a couple of functions:
- FSH is important in the follicular phase of the ovarian cycle, where it stimulates the growth and maturation of follicles in the ovary. A follicle is a group of cells surrounding an immature egg.
- FSH also stimulates the production of the hormone inhibin, whose job is to regulate FSH production.
- FSH indirectly stimulates the production of the steroid hormone estrogen.
Estrogen is released by cells in the developing follicle and has many functions, some of which include:
- Aiding in egg development and maturity
- Stimulating breast development
- Regulating female sexual behavior
- Regulating signaling in the HPG axis
Now, before we can move on to the next step in our HPG pathway, we have to talk about our other gonadotropin. So, file this FSH information away in the back of your mind while we talk a little bit about LH. Then we'll see how everything fits together.
LH is also released from the anterior pituitary in response to GnRH, just like FSH is. However, LH isn't needed until the last stages of the follicular phase of the ovarian cycle. For that reason, most of the LH release is inhibited by low levels of estrogen until the egg has finished maturing.
Once the egg has reached maturity, it produces high levels of estrogen. These high levels now travel up to the hypothalamus, where they stimulate a surge of GnRH. GnRH then causes LH to be released from the pituitary, allowing it to travel to the ovaries, where it triggers ovulation (or release of the mature egg from the ovary).
Here are a few functions of LH:
- LH triggers the completion of meiosis 1 in the developing oocyte, allowing it to reach maturity.
- A surge in LH at the end of the follicular phase triggers ovulation, the rupturing of the follicle wall allowing the mature egg to be released from the ovary.
- Following ovulation, LH aids in the formation of the corpus luteum, a structure that forms from the now-empty follicle and secretes the hormone progesterone.
Progesterone is what helps prepare the uterus for pregnancy. It also feeds back to the hypothalamus to stop, or block, the production of GnRH and GnRH release.
Okay, so now that we have the functions of each gonadotropin and the hormones that they release down, let's look at how all these different hormones interact.
Let's start back at the beginning. First up, GnRH from the hypothalamus travels down to the anterior pituitary. This is where it triggers the release of both LH and FSH from the pituitary. Okay, that's the easy part. The tricky part is what comes next.
See, FSH causes the release of two hormones: estrogen and inhibin. Each of these hormones has a job in our pathway as well. Estrogen is released when FSH stimulates follicle development, and inhibin is released a little later on when FSH is no longer needed.
Meanwhile, while FSH is working, LH isn't needed yet. So, even though GnRH is stimulating LH, only low levels of LH actually reach the ovary. The rest are blocked; they're being prevented from leaving the pituitary by estrogen from the immature follicle. When the follicle and its egg reach maturity, three things happen:
- Inhibin now inhibits FSH because it's no longer needed.
- It creates a large surge in estrogen. This surge goes directly to the hypothalamus, where it creates a surge in GnRH. This surge in GnRH triggers a surge in LH, releasing it from the pituitary.
- The surge in LH triggers the ovulation of the mature egg.
Following the surge in LH, its levels decrease after ovulation. The lower levels of LH help to convert the follicle, whose egg was ovulated, to its next form - the corpus luteum. The corpus luteum will be responsible for the production of progesterone. Once progesterone levels get high enough, they travel back to the brain to tell it to stop producing GnRH, thus bringing an end to our cycle. Once GnRH production stops, the release of all our other hormones decreases as well. Lower GnRH equals lower FSH and LH, which in turn equals lower estrogen and lower progesterone.
Now, if progesterone is inhibiting GnRH from being produced and released, what do you think will happen when progesterone levels drop? Well, without progesterone, there's nothing to prevent GnRH from being released again, right? So, then our GnRH levels start to rise again and the cycle starts all over!
Whew! See, I told you it got a little tricky, but, hopefully you were able to keep up. It might make it easier if you took some time to draw out the pathway on your own. But before that, we'll do one last quick review.
Our female HPG axis involves three main structures: the hypothalamus, the anterior pituitary and the female gonads (the ovaries). Each of these structures receives signals from the others and sends signals back in return. These signals are in the form of hormones, and they communicate their messages by traveling through the bloodstream.
Our first messenger, GnRH, comes from the hypothalamus. It travels to the anterior pituitary, where it triggers the release of LH and FSH. LH and FSH travel to the ovaries, where FSH stimulates follicle maturation, estrogen and inhibin production. This creates steadily increasing levels of estrogen during the follicular phase of the ovarian cycle.
At lower levels, estrogen inhibits LH release while the egg is still maturing. But, once the egg is mature, higher levels of estrogen are produced, and these stimulate a surge in both GnRH and LH. This surge in LH triggers ovulation. You see, when the egg reaches maturity, inhibin feeds back to the pituitary to decrease FSH release. Then, the surge in LH is allowed to stimulate ovulation of the mature egg. After ovulation, LH aids in the formation of the corpus luteum and progesterone production. Progesterone from the corpus luteum then feeds back to the hypothalamus and inhibits the release of GnRH, ending the cycle.
And that's it! I know it's a lot to take in, but if you go back and draw out each step or phase of the pathway, it will really help you in understanding how everything connects. Good luck.
After viewing this video, you'll be able to:
- List the structures and hormones involved in the HPG axis
- Describe how the hormones work together in the HPG axis and explain its overall cycle
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