Hello, we are going to start talking about the male reproductive system. Keep in mind that what we are going to be focusing on is the Hypothalamus-Pituitary-Gonad Axis. So, a lot of this is going to be familiar to you from the endocrine system. In this slide, we have a view through the testes, which is the male gonad that's going to form sperm. And here, you can see a section though a seminiferous tubule that has the epithelial cells of the seminiferous tubule. Sertoli cells, which we'll be talking about as well as many different types of differentiating sperm cells. Here and in the lumen of the tubule, you can see this black kind of flakes, which are nuclei of forming sperm. Before we start talking specifically about the male system, we're going to talk about general principles. One is sexual differentiation. So, how do you become a male or female? That requires, actually, several steps. Unfortunately, several steps that can go wrong. During embryogenesis, germ cells are starting to form in males and females. Whether the primordial germ cells start to form sperm versus egg is going to be determined by the chromosomal sex. An XX forms a female and XY forms a male. AOn the Y chromosome, the expression of a gene called SRY is required to form a testes. Once the decision of having a testes versus an ovary is determined based on XX versus XY, then that will be the gonadal sex. Sometimes the gonadal sex does not match the chromosomal sex. For the instance, if the SRY gene is mutated on the Y chromosome, then an ovary will form even though the person has a chromosomal male sex of XY. They can have a gonadal sex that is female. Once you've established which gonads you're going to have, the gonad is the source of sex hormone, which determines your phenotypic sex. Basically, what do you appear to be. That requires that the gonad is producing the proper hormone and that you have the proper receptors for the hormone in order to have the correct phenotypic sex based on the gonadal sex, and then based on the chromosomal sex. So an example of this is that you need the SRY gene, so that you can form a testes. You also need the testosterone receptor in order to appear to be a male. Whether or not you have the normal testes, you still need to be able to form testosterone and to express the testosterone receptor to appear as a male. There's many steps that are required in order to form properly in terms of gender. We're going to now move to talking about that hypothalamic–pituitary–gonadal axis. We're going to call it the common axis because it's amazing how similar it is between males and females where we're going to have production of gonadotropin releasing hormone from the hypothalamus. And you know from Dr. Jakoi, that release is going to have to be pulatile, so that we don't down regulate the GnRH receptors in the pituitary. We're going to form GnRH in the hypothalamus. That's going to cause production of two different hormones in the pituitary: Luteinizing hormone and follicle-stimulating hormone. Follicle-stimulating hormone when it's released by the pituitary is going to act on the Sertoli cells. The ones that are contacting the sperm, and that will cause them to promote the formation of the sperm. Sertoli cell will also form inhibin, which then will negatively regulate FSH production. LH will act on cells that are outside of the seminiferous tubules. LH acts on cell that aren't indirect contact with sperm called Leydig cells. It will cause Leydig cells to produce testosterone, which will be required for forming sperm and will also act in a negative feedback manner on the pituitary and the hypothalamus. We'll talk about when we get the female reproductive system how similar that is in a female, as well. Inhibin is going to affect FSH secretion. The sex hormone, whether you're male or female, are going to regulate GnRH, LH and FSH production. Let's focus on this left portion of this diagram for right now. The male half of it is where this previous axis that I've already shown was confusing, because the GnRH neurons themselves do not have receptors for testosterone, estrogen or progesterone. But yet, it was known that testosterone negatively regulated GnRH production. Somewhat recently, it's been shown why that is or how this system can still work. It's because there is a second set of neurons that are the ones that actually have the hormone receptors. These are called Kisspeptin neurons because they make a neurotransmitter called kisspeptin, which binds GRP54 receptors on the GnRH neurons. In the male, when testosterone is formed, testosterone binds the kisspeptin neurons and causes a decrease in kisspeptin release, which then causes a decrease in GnRH release by those neurons in the hypothalamus. So, the kisspeptin neurons explain why testosterone has its effects even though GnRH neurons do not have testosterone receptors. We'll talk about this system in the female. This system is also going to be important during puberty. Kids express very low levels of sex hormones, like testosterone and estrogen. Yet that small amount of estrogen or testosterone results in very low GnRH production. This is because at this time, the hypothalamus and presumably, the kisspeptin neurons are very sensitive to the sex hormones. However, as the puberty approaches, somehow and it's not completely understood how, the neurons in the hypothalamus become less and less sensitive to the sex hormones. So that, that same level of testosterone will allow more GnRH to be produced, which will then cause more testosterone to be produced and that will continue. The hypothalamus becomes less and less sensitive to sex hormones until we get to the adult amount of sensitivity. And so, that's what changes during puberty to allow you to have the adult axis of hypothalamus-pituitary-gonad. We've talked really only about cases that are very similar between males and females where we're going to have the formation of germ cells and the synthesis of sex hormones. These are going to happen in the male and female gonad. We're going to have secretion of GnRH from the hypothalamus, which is going to control FSH and LH from the pituitary, again, both in males and females. That FSH and LH are going to be what's responsible for producing the germ cells of the male and female, and the sex steroids, and then the sex steroid will feedback negatively through kisspeptin neurons on FSH, and LH. There'll be a one exception in the female that we'll talk about. So the sex steroids are going to be required for fertility, for the formation of gonads, but also for appearing as a male or female for the secondary sexual characteristics.
