Male reproductive hormones Flashcards
Learning Outcomes
*Outline the main hormones and cell types involved in the endocrine regulation of reproductive physiology
*Explain the major aspects of male reproductive physiology & its endocrine control of Spermatogenesis
*Describe the occurrence and causes of male infertility
Gonads
So we’re going to start off this lecture looking at what parts, um,
of the anatomy are important for males and for the production of the male hormones.
So the organs that produce the gametes are known as they the sexual reproductive organs.
And they also secrete hormones. So in males this is the testes that are located here.
And you’ll see that there’s this nice long tube.
The vas deferens that comes all the way through.
Alongside the bladder
And then it comes all the way down and through the prostate.
Now, the prostate is an important organ .
. So in females, this is equivalent to the ovaries.
Okay. And the fallopian tubes. Okay.
So this is where Theyre. Similar in some ways.
Spermatogenesis
When we zoom into the testicles.
These are the most important place. Okay.
The testes are where the hormones are generated.
So what you can see up here is almost like a cross-section through the testes.
And what you see is that they are separated out into almost little sections And these little sections called lobules have a wiggly tube that’s inside.
This is known as a seminiferous tubule. Okay.
And this is where all of the spermatozoa are generated.
So that’s why they are the most important thing.
And actually those seminiferous tubules where spermatogenesis happens to generate spermatozoa.
There are about 2 to 300 of these in a lobule.
Okay. And of course. That means that we have large numbers of these.
When spermatogenesis is taking place, it takes about 65 to 75 days to generate spermatozoa.
So if you’ve seen something that says these go in three month cycles, this is what it means.
Okay. It takes about 65 to 75 days to generate the spermatozoa.
Okay. So this is why these structures are important.
And what you’ll notice is these seminiferous tubules all amalgamate together in the middle here.
And then what will happen is they will be taken out via.
This. Epididymis or ductus epididymis.
Which is going to take them out and then through the prostate and out into, um, the outside world.
Okay. Now the prostate is important partially because it makes fluid that is secreted into the semen.
Okay. It produces a solution that is basic.
The pH is really important to activating the spermatozoa.
So, for example, usually where they’re generated here in the seminiferous tubule it is quite an acidic environment and they’re not very active.
But once there is addition of this more basic solution to the semen, then it activates and allows greater movement of the spermatozoa.
Spermatogenesis production
So in terms of spermatogenesis, what’s happening inside the seminal tubule is that his seminal first tubule is protected by this basement membrane.
It’s protected by that because it’s really important that these cells that are generated here are going to go on and make.
Your offspring. Okay. That means that their genetic information is really precious because that’s what’s going to keep the human race going.
Okay. So this really tight basement membrane around the outside just makes sure that as much as possible, nothing can get in.
Okay. Nothing can hurt that genetic information.
So that basement membranes there. And then what we have are two spermatogonium
that have got a normal amount of DNA they’ve got two n meaning they’ve got a copy from each of their parents of each, chromosome.
These spermatogonium, are stem cells. Okay, so when they divide one of the offspring,
one of the daughter cells stays and replaces that original cell, okay, so that it’s self-replicating.
So there’s always a cell there ready to generate more spermatozoa.
However, the other one is the one that moves further away from the basement membrane, and it moves physically towards the lumen of the seminiferous tubule.
that’s where the basement membrane is.
And the part down at the bottom of the diagram is the lumen of the seminiferous tubule so it’s moving towards the inside of the tube.
When this process happens, there is some differentiation that happens and we generate primary spermicide.
Okay. This primary spermicide has divided by mitosis means it’s got the same amount of DNA.
Okay, so at this point, it’s exactly the same DNA replication happened.
Um, there’s been a small amount of crossing over has happened, and it’s sat here.
Then it undergoes meiosis one, meiosis of course generates two daughter cells. Each with 1n Genetic content, so it separates its two copies into
Two cells with half the amount of DNA. So it’s got one copy each
Of half of the amount of DNA from each of the original parents Okay. And so this means that now is at a point where if it joins with Another gamete from a female individual, for example, that you would generate. A viable diploid cell. Okay. So at this point they’ve each got two chromatids right.
Got two chromatids but one copy of each chromosome.
So at this point then when they go through mitosis again they generate four offspring because it copies exactly the amount of DNA that was in here.
Again to make 4 spermatids.
Now what you’ll notice between the 2 secondary spermatocytes is that there is what we call a cytoplasmic bridge that happens between the two where cell division has happened.
But there’s quite a lot more cytoplasm than it needs, okay.
Because when it goes through this reductive process, it needs to generate the spermatozoa which has very little cytoplasm.
Its main objective is to swim.
Its main objective is not to be large and have lots of cytoplasm.
Okay, so it goes through this reductive process,
and that cytoplasmic bridge enables there to be an equilibrium and to make sure that one cell is not huge and the other cell is tiny.
Now that cytoplasmic bridge is maintained, when they go through replication again to generate the sperm,
it’s and that cytoplasmic bridge slowly gets removed as the cells start to shrink their cytoplasm.
That fluid is taken up by the cells around these spermatozoa that form that nice pink background that we haven’t talked about yet.
Okay. And then we now generate spermatozoa.
And you can see how this requires a lot of differentiation.
They’re completely different. There’s this nice long tail.
They’ve got kind of pointy arrow looking heads in comparison to these big round blobs that are the sperm.
soe that last final step to generate our spermatozoa is a differentiation step a specialisation step.
Now once they are generated those matters will then be released into the seminiferous tubule where they’ll accumulate over time until they’re required.
Okay. So they sit here and then they’re bathed a sort of adjusted semen.
Sertolicells
And so now we look at the cells that are around those spermatozoa as they’re going through spermatogenesis.
Okay. So what we’ve got here is this is our seminiferous tubule.
And within them the spermatozoa that are being generated.
And the cells around the inner border of the seminiferous tubule that contain the spermatozoa are called Sertoli cell.
And they nourish those spermatozoa as they’re being created.
You’ll also notice that there’s this Leydig cell on the outside of that basement membrane.
That’s important for later. And there’s a nice blood cell next to it.
So these sertoli cells through which those spermatozoa are being generated during spermatogenesis.
They’re really important because what they do is not only do they create nutrients that
will keep those spermatozoa able to do metabolic processes and undergo differentiation,
but they also take up that large amount of cytoplasm that we discussed how it was needed to be gotten gotten rid of.
They will take up that cytoplasmic volume.
And they also produce hormones. And we’ll talk a little bit more about what hormones they are in a minute.
But what you’ll see here is that in the second diagram you can see much more specificity, about what is the sertoli cell, it is connected the basement membrane and filled with spermatogenic cells that are undergoing the division process.
And as the spermatogonium separates off from the basement mambrane, it is going to push down between the Sertoli cells.
so these spermatogenic cells are not totally in the Sertoli cells
They’re sort of weaning their way between them.
Because if you remember, our cells are next to each other, but they don’t have to be connected to each other.
now in the right hand side diagram you can see the basement membrane again that we mentioned that’s held together by tight junctions.
Okay. And it’s not possible to, penetrate that.
That’s a really important part of having those tight junctions.
Sertoli cells FUNCTIONS
So in terms of the Sertoli cells,
their function is that they are joined by tight junctions and they’re part of the blood testis barrier.
Okay. And that protects that genetic information.
They nourish the spermatozoa. It’s the spermatids. and the sperm.
And they phagocytose the excess spermatid cytoplasm.
they also produce the fluids that forms part of that semen.
For transport out of the body in terms of their endocrine function.
They produce a hormone called inhibin which we’ll find out what that does in a minute.
And they regulate the effects of testosterone.
And as a result of that, they regulate the production of follicle stimulating hormone (FSH)
Leydig Cells
So now we’re going to look at those leydig cells that I talked about a bit earlier that are on the outside of the barrier.
These are in the spaces between the neighbouring Seminiferous tubules.
Okay. And their main function is the production of testosterone.
And you’ll notice that in this diagram they’re quite close to the blood vessel.
And the reason for that is that although they’re producing testosterone for the seminiferous tubule to enable spermatogenesis to happen,
they’re also producing that testosterone that’s going to circulate the body as well.
Okay. So it’s not just going one place, it’s going everywhere.
But the strongest concentration will be in the testes because they’re right by the source.
Okay. So in terms of what these look like in that diagram, we were looking at just now that these kind of green ones at the top here.
And as you notice it, unlike the sertoli cells, they pretty much have one function, and that one function is to produce testosterone.
Testosterone
Testosterone
Now, what’s special about testosterone? It’s considered to be an androgen, meaning that it has androgenic effects.
Okay. And we’ll talk about what those androgenic effects are in a minute.
For those of you who are doing biochemistry, you probably will have seen a structure looking very similar to this in our lecture slides last week,
where we looked at things that are generated from cholesterol.
Okay. Testosterone is generated from cholesterol.
It has those four ring structures okay.
And it acts by binding to a nuclear receptor, okay.
That nuclear receptor is the androgen receptor.
So now you can see the link not only to any biochemistry that you’ve done but also.
To your molecular biology. We talked about nuclear hormone receptors.
This is one of those. Okay. So.
Testosterone, as we mentioned just now, secreted by the leydig cells.
And what happens is, is that testosterone that I said goes into the bloodstream.
well Very close by to it We’ve got the prostate.
And in the prostate there’s an enzyme called five alpha reductase, which converts the testosterone into dihydrotestosterone.
And you can see the difference in their structure down at the bottom.
There’s not a lot of difference. However, instead of these ring structures on the testosterone which have a carbon-carbon double bond across them.
We’ve now got two hydrogen bonds added on the dihydrotestosterone. So that’s insinuated by this dye hydro part here okay.
So the difference is just removing the carbon-carbon double bond and giving it two hydrogens.
Now the difference between these is that the dihydrotestosterone has a slightly different affinity for the receptor.
So it’s able to activate it much more strongly. So it has the more peripheral effects that you see, that are caused by testosterone
Testosterone physiological effects
So what are those physiological effects?
Well, when, a foetus is being created, and is growing, then this can cause, the descent of the testes.
So when they’re first generated, they’re sort of further up the body incorporated in the body,
but in preparation for birth, where the testes will be at a different temperature to the rest of the body.
There has to be a descent of those testicles to be able to maintain that.
Whereas when they’re in utero, everything’s the same temperature.
Okay. They’re also part of a negative feedback loop that control sperm.
Okay. So testosterone is generated.
And if the concentrations are really high there will be something that goes.
Remember from last year when something is really high and it goes outside the normal range,
there’s something that says reduce the amount of testosterone that’s being produced and then it will drop again.
Okay. And if it drops outside the bottom end then we start turning it back on again.
Okay. So that’s that negative feedback process.
So if we get too many spermatozoa being generated testosterone will reduce.
And so that will enable the reduction in production of spermatozoa.
It also controls beard growth.
Voice deepening. Lots of people going through, um, puberty.
that’s when this process is happening.
Because as the levels of testosterone rise and then fall again,
it has it has these effects on changing the voice box, allowing that voice deepening beard growth as well.
You suddenly go from having no facial hair to having to shave every day.
Okay. All those kinds of thing. And there’s also anabolism, as you start to gain muscle.
Can you think of often the difference between females and males in terms of muscle composition is males have a lot more muscle in their legs, for example, than females will. So it’s thinking about those physical changes that might happen as a result of the rise in testosterone.
Pause and think
Uh, why do you think that hormones become so prominent during puberty?
And what are the events that occur in target cells that cause the effects that we see as a result of that hormone?
So why do you think things become prominent? What’s the cause of these hormones becoming prominent during puberty?
What controls all those hormones that you’ve just been talking about with Professor Johnson?
Hypothalamus? Absolutely. It’s the control centre of everything that goes on in terms of hormones.
Absolutely. So something changes in the hypothalamus.
And what’s the reason why this might happen?
Prepare you for reproduction. Lovely. Okay. So it’s about timing and making sure that everything’s happening in the same time.
There’s no point having developed sexual reproductive hormones if your brain is not ready for this or.
And it’s not also not no point in having some areas of the body ready but not others.
Okay, so it’s about timing everything. So everything’s ready at the same time and prepared.
What are the events that occur in the target cell that cause the effects that we see of this hormone?
So where does this start?
If you’re doing biochemistry or experimental biology, you can quietly slap yourself in a corner if you don’t know the answer to this question.
What has to happen to your hormone. It binds to.
Uh, a receptor? Absolutely. So your hormone has to bind to a receptor.
This starts this whole thing off. Okay.
If that doesn’t happen, then there will be no physiological changes.
So just remember to join those dots. You have done a little bit about receptors and the binding of hormones in this module.
It might not be as detailed as other modules and that’s perfectly fine.
But you can build that information in if you know it.
Spermatozoa
Okay, so if we took our spermatozoa, then because they’re the thing that does the business and gets to the point where we can enable reproduction to occur.
This is what our spermatozoa looks like. And of course, it contains 23 chromosomes rather than 23 pairs.
Okay. And what you’ll notice is that this little green bit around the outside is called the acrosome
And that’s got enzymes that will degrade the surface of the secondary oocye.
To allow fertilisation to happen. Okay.
So this needs to happen to enable that sort of really protective outer surface of the oocyte to enable the head part,
which has got that 23 chromosomes to then fuse with the oocye.
Okay. From the female. What we’ve got in the middle here.
This middle piece.
This middle piece is full of mitochondria.
What’s a mitochondria generate? ATP.
Lovely. So the reason why we’ve got that ATP is because it needs to spin the tail.
It’s the thing that has lots of microtubules in it.
So it literally spins round and propels the spermatozoa.
And so this is really important because the middle piece is where all of those microtubules attach to.
So they’re all working with each other okay.
And they attach to the centrioles right.
The principal and end pieces. So that very tiny bit at the very end.
Form part of the tail. And that’s how it moves along, almost in that sort of whipping motion.
Generally. Um.
These. Go exceptionally fast.
But remember, in comparison to their size, how far they’ve got to go.
Once they enter, the female is the equivalent of several marathons.
Okay, so although they swim fast, they also have to live.
They also live for a very short time, which is why this process is not 100% efficient.
Okay. And in fact. It’s not very efficient at all.
What regulates Spermatogenesis?
So. If we look at what regulates spermatogenesis.
As I mentioned just now, you identified the hypothalamus is really important in this.
And with Professor Johnson you will have talked about the anterior pituitary.
And you would have talked about the thyrotroph cells that secrete TSH or thyroid stimulating hormone.
And you will have talked about the corticotroph cells that are also located here which secrete ACH.
However, we’re going to talk at the moment about these gonadotroph cells that secrete follicle stimulating hormone or FSH, and luteinizing hormone LH.
So what happens here is that in the anterior pituitary, just like you have had previously, the hypothalamus secretes gonadotropin releasing hormone.
Which is going to come down the hypophyseal portal system to the hypophyseal vein, and it’s going to activate those gonadotroph cells to secrete FSH and LH,
which is then going to be transported to the ovaries.
What regulates Spermatogenesis?- hormone
So. The gonadotropin-releasing hormone is controlled by negative feedback.
The more there is a bit, the more FSH and LH there is that’s generated.
The other hormone that can control the release of luteinising hormone and follicle stimulating hormone is inhibin.
Okay. And this is generated in the testicles by the release of testosterone.
So if the levels of testosterone get too high, then inhibin will be secreted to inhibit the release of follicle stimulating hormone.
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Hormonal regulation of Spermatogenesis
So. The gonadotropin-releasing hormone is controlled by negative feedback.
The more there is a bit, the more FSH and LH there is that’s generated.
The other hormone that can control the release of luteinising hormone and follicle stimulating hormone is inhibin.
Okay. And this is generated in the testicles by the release of testosterone.
So if the levels of testosterone get too high, then inhibin will be secreted to inhibit the release of follicle stimulating hormone.
Okay. So it works a little bit like this.
And on your sheet you have got a link to a video that will show you these,
bits that are in this diagram actually twisting and turning as they come down and telling you how everything is organised in time.
So. The hypothalamus is going to secrete gonadotropin releasing hormone.
And that’s going to go through the hypophyseal circulation to the anterior pituitary.
Those gonadotroph cells are going to release FSH and LH.
These are released and packaged in the same Vesicle.
Okay, but they’re not in a 1 to 1 ratio.
So there might be slightly more LH than there is FSH in that vesicle.
Okay. And when they’re released luteinizing hormone is going to stimulate testosterone production from the leydig cells okay.
Those leydig cells remember they’re the ones that are outside the basement membrane.
So is going to increase the amount of testosterone, both in the body and also in the testes.
And you can see the testosterone here in the diagram.
So this represents it going out elsewhere for example through the prostate where it will get converted to dihydrotestosterone which is mainly uh,
responsible for those male pattern development before birth and enlargement of the male sex hormones.
Inside the testes though, they’re going to stimulate.
The sertoli cells are going to support the production of sperm through spermatogenesis okay.
In response to stimulation by testosterone.
The sertoli cells will generate a protein called androgen binding protein or ABP.
ABP is a little bit like a chaperone, and it says you need to stay in the testes and it stops the testosterone from moving straight out of the testes.
That’s needed.
Because if you remember, if you’re doing biochemistry, that testosterone is lipid based so it can move straight through the membrane without any help.
So it would be a little bit like me trying to keep water in a sieve.
If we didn’t have that protein to bind to it and stop it from getting out.
Okay, so the testosterone is kept in the testes at a high concentration by that androgen binding protein.
Okay. Now if the testosterone levels get too high, what can happen is, is that the testosterone will of course enter the general circulation.
And once it reaches a particular threshold, there’s so much of it.
There are receptors that are in the hypothalamus that, once they’re saturated,
will start to reduce the amount of gonadotropin releasing hormone detected in the hypothalamus.
So that will reduce gonadotropin releasing hormone release and that will reduce luteinizing hormone and follicle stimulating hormone.
And that will reduce spermatogenesis from happening and testosterone release.
So it’s a self regulating circle.
Now for spermatogenesis to happen.
It doesn’t just require testosterone. It also requires FSH which.
So follicle stimulating hormone must be present in addition to.
Testosterone. Otherwise, if you don’t have both of those.
Then spermatogenesis won’t occur. Okay.
And so the second way that we can regulate this process is through the reduction of the release of follicle stimulating hormone.
So inhibin that’s generated by the sertoli cells is able to feed back.
That there’s way too much testosterone here in the testes.
Let’s just calm things down a bit.
inhibin can reduce the release of FSH, reduce the amount of spermatogenesis that’s going on, and calm this system down.
So if there are lots of spermatozoa that have been generated and you don’t want any more to continue to happen
That is one of the ways, in combination with testosterone regulation that it would reduce the amount of spermatogenesis happening.
Hormonal regulation of Spermatogenesis GnRH stimulation
Male reproductive system -Summary
Male reproductive system -Summary- outline of main hormones
what are the things that can go wrong
Um, usually the reason why things go wrong can be because there’s a deficiency of the hormone in terms of how much is generated.
It could be that there’s an imbalance of hormones.
So say you’ve got loads of inhibin but your testosterone is normal.
That still would affect spermatogenesis okay.
So it’s the imbalance of hormones. Or perhaps there’s a problem with one of the receptors involved here.
Because whenever we’re talking about a hormone being released it’s got to be recognised by the receptor.
Okay. So there are three main areas where things might go wrong.
