0:00 hello and welcome to the second part of
0:01 the endocrine physiology chapter of
0:04 costanzo's physiology textbook
0:06 in this video we are going to go over
0:08 the hypothalamic pituitary axis
0:10 which is essentially the mastermind
0:12 that's able to control the majority of
0:15 our endocrine systems
0:16 it consists of the hypothalamus which is
0:18 clearly up in the brain which we covered
0:20 in the neurology portion
0:22 and then also the pituitary gland that
0:23 kind of sits just underneath it
0:25 the pituitary gland is made up of two
0:28 separate glands
0:30 or two separate lobes the posterior lobe
0:33 which is called
0:34 also the neural hypothesis mainly
0:36 because it's made out of neuron cells
0:39 and secretes neuropeptides and then we
0:42 have the anterior lobe
0:44 which is also called the adeno
0:45 hypothesis which is actually made out of
0:48 endocrine cells
0:49 themselves so you can see it over here
0:52 figure 9.9 here
0:54 where we have the posterior lobe made
0:56 out of neurons and you can see that the
0:58 cell body
0:58 of the neuron is actually located within
1:01 the hypothalamus
1:02 and then also the anterior lobe made out
1:05 of endocrine cells
1:07 which is connected with the hypothalamus
1:09 with a bloodstream its own hypothalamic
1:11 hypophyseal portal vessels so this is
1:14 essentially the venous system
1:16 to the hypothalamus so then the anterior
1:19 lobe of the pituitary gland receives
1:21 high concentrations
1:23 of the hormones from the hypothalamus
1:25 that does not enter the systemic
1:26 circulation
1:28 and that directs which hormones should
1:30 be released from
1:31 the anterior pituitary gland once either
1:34 the posterior or anterior pituitary
1:36 gland is stimulated to release a certain
1:37 type of hormone
1:38 that just gets released into the
1:40 systemic circulation
1:41 now the posterior pituitary gland only
1:44 secretes
1:44 two neuropeptide hormones adh
1:47 and oxytocin adh is primarily associated
1:51 with the supraoptic nuclei within the
1:53 hypothalamus
1:54 whereas oxytocin is primarily associated
1:57 with the paraventricular nuclei in the
1:59 hypothalamus
2:01 so how this works is that the hormone is
2:03 actually synthesized in the cell body of
2:05 the neuron within the hypothalamus
2:08 and then actually gets transported to
2:10 then sit in vesicles
2:11 right at the end of the neuron and the
2:13 dendrites waiting to be stimulated to be
2:16 released when told so
2:18 by the hypothalamus whether that's adh
2:20 or oxytocin we'll go into more details
2:23 about those two different hormones
2:25 later on in this video and to start with
2:27 we'll talk about the
2:28 anterior pituitary gland hormones
2:30 because we have six
2:31 major hormones here and each are
2:33 secreted by their own
2:35 cell type ending in troph for example
2:38 we have thyroid stimulating hormone or
2:40 tsh released from
2:41 thyrotropes we have acth
2:45 released from corticotropes we've got
2:47 growth hormone released from
2:48 somatotropes
2:50 prolactin from the lactotrophs and then
2:52 lastly follicular stimulating hormone
2:54 and luteinizing hormone
2:56 fsh and lh secreted by gonadotrophs so
2:59 these
2:59 tropes a particular endocrine cells
3:01 within the anterior pituitary gland that
3:03 secretes its own endocrine hormone
3:06 when stimulated too from the release of
3:09 a releasing hormone from the
3:10 hypothalamus
3:12 so hypothalamus secretes a releasing
3:14 hormone in response to a stimuli that
3:16 releasing hormone
3:18 tells the stimulating hormones from the
3:20 pituitary gland to be released which
3:22 then get released into the systemic
3:23 circulation
3:24 and then these stimulating hormones go
3:26 to their target endocrine glands within
3:28 the body
3:29 to then stimulate the release of the
3:31 hormone that they want to release
3:33 so for instance when it comes to thyroid
3:34 hormone which we'll go in in another
3:36 video
3:37 the hypothalamus releases thyroid
3:39 releasing hormone which then tells the
3:41 anterior pituitary gland to release
3:43 thyroid stimulating hormone and the
3:45 thyroid stimulating hormone tells the
3:47 thyroid gland to release
3:49 thyroid hormone so that's the basics
3:51 behind the
3:52 hypothalamic territory axis so going
3:55 through
3:55 some of the particular hormones released
3:57 from the anterior pituitary gland
3:59 specifically now
4:01 just briefly tsh fsh and lh are all
4:04 glycoproteins it goes into a little bit
4:06 of detail about their actual molecular
4:08 structure which i don't think is as
4:09 important but essentially they are all a
4:11 similar type of protein a glycoprotein
4:14 tsh we will go into more details in the
4:16 thyroid hormone video which will be
4:18 coming up shortly
4:19 and then fsh and lh will be in the
4:21 reproductive tract is
4:22 acth or adrenocorticotrophy hormone
4:26 is released from the anterior pituitary
4:28 gland to
4:29 increase the secretion of our adrenal
4:32 cortical hormones from the adrenal gland
4:34 we will go into much more details about
4:36 that actually in the adrenal video
4:38 coming up i know
4:39 this seems ridiculous that we're going
4:40 to go over these in more detail later
4:42 but these are the major hormones that we
4:44 will be covering in much more detail
4:46 in a later video so acth is slightly
4:49 different to these other ones and how it
4:51 is formed within the anterior pituitary
4:53 gland you can see that
4:54 ac th actually comes from originally
4:56 this molecule called pomc
4:58 or pro opio melanocortin the main point
5:01 here
5:02 is that although we get acth getting
5:03 produced we do have these
5:05 other and the fragments of acth that can
5:08 also have a minor effect and more
5:10 importantly if we have a high production
5:12 of acth we will get increased of these
5:14 other fragments
5:15 and more important clinically is the
5:18 production of
5:19 the melanocytes stimulating hormones the
5:21 msh hormones
5:23 so these hormones will actually cause
5:25 skin pigmentation so then that will
5:27 cause
5:27 clinical signs in the presence of
5:30 excessive acth or end up with
5:32 increased skin pigmentation so we'll go
5:34 into growth hormone in more detail
5:36 now so growth hormone is also released
5:38 from the anterior pituitary remember
5:40 from the somatotropes
5:42 the growth hormone as the name implies
5:44 is important for growth
5:46 so it does that by altering our protein
5:48 carbohydrate and fat metabolism
5:50 it gets stimulated to be released from
5:52 the anterior pituitary gland
5:54 due to growth hormone releasing hormone
5:57 from the
5:58 hypothalamus and that occurs in a
6:00 pulsatile way every
6:02 roughly two hours and also has some
6:05 other stimulatory
6:06 factors as well all noted in table 9.4
6:09 here
6:09 in addition to its inhibitory factors
6:11 the best way to think about this
6:13 is that anything that will be inhibiting
6:16 growth so let's say you don't have
6:17 enough nutrients
6:18 then your growth hormone will be
6:20 stimulated to increase those nutrients
6:22 in your body
6:22 so growth hormone is trying to provide
6:24 an environment for you to grow
6:26 so if you have decreased glucose
6:28 decreased free fatty acids
6:30 you're fasting or you're exercising
6:32 you're under stress then you're going to
6:33 release growth hormones to try and
6:35 provide an environment for you to
6:36 actually grow
6:37 obviously when you're going through
6:39 puberty you have higher growth hormone
6:40 during those times as well growth
6:42 hormone will then steadily decrease as
6:44 you get older now our inhibitory factors
6:46 are going to be the opposite of those so
6:48 if we have high glucose high free fatty
6:50 acids then we already
6:51 kind of have an environment for growth
6:53 so you don't need to release your growth
6:54 hormone
6:55 obesity reduces it some metastatin
6:58 remember that's our stop hormone from
7:00 our gi chapter somatostatin
7:02 also plays a role with inhibiting our
7:04 growth hormone effects as well
7:06 growth hormone itself actually inhibits
7:08 itself there are negative feedback
7:10 mechanism and then circling back to
7:11 somatostatin
7:12 this is an example of a gi protein
7:15 coupled receptor remember we talked
7:17 about the gs
7:18 protein receptors which cause an
7:20 increase in cyclic amp
7:22 gi proteins are inhibitory g proteins
7:25 they reduce the level of
7:26 cyclic amp by inhibiting the admiral
7:28 cyclase enzyme
7:30 so somatostatin the stopping hormone
7:32 which inhibits growth hormone does so
7:34 by interacting with a gi protein
7:38 as a receptor so figure 9.11 here
7:41 tells us how growth hormone has a
7:43 negative feedback on itself
7:45 the first thing to point out here is
7:46 that when growth hormone actually has
7:48 its effect on the target tissue
7:50 it gets broken down into these
7:51 somatometers or igf's
7:54 these igfs then actually have an
7:56 inhibitory role
7:57 on the release of further growth hormone
7:59 by having a direct effect on
8:01 inhibiting our anterior pituitary gland
8:04 but then also
8:05 by having a stimulatory effect on the
8:07 hypothalamus to release somatostatin
8:10 remember somatostatin our stopping
8:11 hormone inhibits also the anterior
8:13 pituitary gland
8:15 so that's one way the growth hormone has
8:17 negative feedback on itself
8:19 when it's broken down the byproducts
8:21 have an inhibitory effect growth hormone
8:23 itself
8:24 also has an inhibitory effect on itself
8:26 by
8:27 increasing the release of somatostatin
8:28 from the hypothalamus so
8:30 increased growth hormone will actually
8:32 self-regulate itself
8:33 and the last mechanism out of the three
8:36 is
8:36 growth hormone releasing hormone
8:38 actually having an inhibitory effect
8:40 on the hypothalamus itself so although
8:42 it's released from the hypothalamus as
8:44 soon as that increases in concentration
8:46 it's going to tell itself to stop
8:48 secreting itself
8:49 essentially so the growth hormone that
8:51 negative feedback mechanism has these
8:53 three different
8:54 feedback systems somatometers growth
8:57 hormone and growth hormone releasing
8:59 hormone
8:59 so how does growth hormone actually have
9:02 an effect
9:03 on the body we know it's used to promote
9:05 growth but what is it actually doing
9:07 well we have three main effects here to
9:09 remember number one
9:11 is being diabetogenic or having an
9:13 insulin resistant
9:15 effect it blocks the effects of insulin
9:17 which is trying to reduce your glucose
9:19 levels in your body or in your blood
9:21 so by blocking or making insulin
9:23 resistant you increase the amount of
9:25 glucose in your bloodstream
9:27 and then it also increases lipolysis and
9:29 adipose tissues
9:30 basically what this is doing is
9:32 increasing our energy stores and our
9:34 plasma
9:35 so then our body has a lot of energy to
9:37 be able to grow
9:38 so we're increasing energy availability
9:41 by antagonizing insulin in an effect for
9:43 an easy way to think about that first
9:45 effect our second effect
9:47 is increasing growth by stimulating
9:50 protein synthesis and organ growth so
9:52 we're increasing the uptake of amino
9:54 acids into
9:55 our cells and we're increasing the
9:57 stimulation of protein development this
9:59 will increase
10:00 lean body mass and organ size our third
10:03 effect
10:04 is an increased in linear growth so
10:06 before puberty before your growth
10:09 plates have used it will increase the
10:11 production of bone within your growth
10:13 plate so then you're able to grow you
10:15 know this is why during your growth
10:16 spurt your
10:17 high growth hormone but then if you're
10:19 already finished your growth it will
10:21 actually
10:21 increase our periosteal bone growth so
10:24 kind of the
10:24 edges of our bones so we have this
10:27 influence on bone growth
10:28 more dramatic obviously before puberty
10:31 that brings
10:32 us to when we have an issue with our
10:34 growth hormone
10:35 if we have deficiency then that's going
10:37 to lead into dwarfism which is treated
10:40 with
10:40 growth hormone with excess what you're
10:42 going to see depends on when this occurs
10:44 if it's before puberty
10:46 then you end up with gigantism because
10:48 you're actually
10:49 increasing your long bone growth after
10:52 puberty
10:52 when linear growth is complete then you
10:55 end up with just
10:55 larger features so larger facial
10:57 features larger hands
10:59 increased organ size insulin resistance
11:02 glucose intolerance etc from that
11:04 excessive growth hormone so that is
11:06 growth hormone in a nutshell
11:08 next up is prolactin now prolactin is
11:11 responsible for milk
11:12 production so producing milk not letting
11:15 it down that's oxytocin
11:16 but milk production and the development
11:19 of the breasts
11:20 so obviously we're going to have an
11:21 increased secretion of prolactin during
11:24 pregnancy and lactation
11:25 now the thing with prolactin secretion
11:28 from the anterior pituitary gland which
11:30 works on the breasts
11:31 is that on the day-to-day it's getting
11:33 inhibited from dopamine release from the
11:35 hypothalamus
11:36 up until pregnancy or lactation that's
11:39 when that gets overridden and we
11:41 start to increase trh release trh
11:44 stimulates the release of prolactin and
11:46 prolactin nature has an
11:47 inhibitory effect on itself for its own
11:50 negative feedback by increasing the
11:51 level of dopamine
11:53 so the stimuli for prolactin release
11:56 is suckling that's the main stimulation
11:59 so
11:59 obviously that's a need for lactation
12:01 after pregnancy
12:02 then you're going to increase milk
12:04 production there is also another time
12:06 for
12:07 prolactin release which is that puberty
12:09 for breast development but otherwise
12:11 it only gets released during lactation
12:13 in order to produce milk for the baby
12:15 any pathophysiology of prolactin
12:17 includes deficiency where obviously you
12:19 fail to lactate and then
12:21 excess which can occur due to some kind
12:23 of prolactin producing tumor which can
12:25 lead to infertility because prolactin
12:28 does inhibit ovulation and also
12:30 galactoria or excessive milk production
12:32 so moving on to
12:33 our posterior lobe hormones now remember
12:35 we talked about adhd and oxytocin
12:38 as our two posterior pituitary gland
12:40 hormones produced
12:41 and synthesized by the cells within the
12:44 hypothalamus in the neuron
12:46 but then that neuron extends all the way
12:48 down into that posterior pituitary gland
12:50 where it sits waiting to be
12:52 stimulated to be released so adh
12:55 is the first one that we'll focus on
12:57 here this gets secreted
12:59 whenever we have a depolarization of
13:01 that nerve
13:02 that the adh is sitting in that
13:04 stimulates calcium and to enter the
13:06 terminal and causes exocytosis
13:08 of the adh and also the oxytocin when we
13:11 get to talking about oxytocin
13:13 now we've already talked about adh in
13:15 our renal chapter remember adh is
13:17 involved with controlling our oils
13:19 predominantly and then also an influence
13:21 on controlling our blood pressure
13:24 now our hypothalamus will sense if our
13:27 osmolarity will change
13:28 if there is an increase in osmolarity
13:30 then that stimulates increased
13:32 adh secretion adh goes to the kidneys
13:36 and then tells the kidneys to increase
13:38 the reabsorption of water
13:40 it's able to do that by actually
13:42 interacting with a v2 receptor which is
13:44 a gs
13:45 protein to increase cyclic amp in the
13:48 principal cell of the
13:50 late distal tubule and cortical tubules
13:52 that will ultimately end up with the
13:54 phosphorylation of
13:55 aquaporin two proteins that insert
13:57 themselves into the membranes
13:59 aquaporin ii results in increased
14:02 permeability of those principal cells to
14:04 water so now that terminal nephron can
14:06 actually absorb water when it was
14:07 previously impermeable
14:09 so the absorbing of water from the
14:11 nephron reduces the osmolarity in our
14:13 plasma
14:14 and helps to restore our osmolarity now
14:16 if we also need to increase the water
14:18 reabsorption from our kidneys because of
14:19 hypotension
14:21 then that will occur because our dairy
14:23 receptors within our carotid artery and
14:26 aortic arch
14:27 will sense a low blood pressure that
14:28 will transmit a signal via the vagus
14:31 nerve to the hypothalamus
14:33 and then that will tell the hypothalamus
14:34 to stimulate the release of adh to
14:36 increase water reabsorption to help to
14:38 increase our blood volume again
14:40 and blood pressure now adh also has
14:42 another influence to help with blood
14:44 pressure
14:45 through contraction of our vascular
14:46 smooth muscle via the v1 receptor so v1
14:50 for vascular smooth muscle contraction
14:52 v2 for aquaporin 2
14:54 and increasing water reabsorption from
14:57 the kidneys
14:58 now interestingly the v1 receptor for
15:00 the vascular smooth muscle
15:02 actually utilizes the ip3 calcium
15:04 secondary messenger system
15:06 versus the v2 receptor which utilizes
15:08 the cyclic amp
15:09 secondary messenger system so when it
15:11 comes to disorders of
15:12 adh we have central diabetes insipidus
15:15 and nephrogenic diabetes
15:17 insipidus diabetes insipidus just means
15:20 very watery urine or very dilute urine
15:22 now
15:23 that occurs because we have an
15:25 inappropriate response to adh either
15:28 because we don't have
15:29 enough adh such as in central diabetes
15:32 insipidus where there is no secretion of
15:34 adh
15:34 from the posterior pituitary gland at
15:37 all which needs to be treated by
15:38 giving an adh analogue like ddavp or
15:42 nephrogenic diabetes insipidus where the
15:44 principal cells are actually
15:45 unresponsive to adh altogether
15:48 now these will not respond to adh
15:51 analogues and will actually require a
15:53 different type of treatment like
15:54 thiazide diuretics to help to reduce our
15:57 sodium reabsorption to increase our
15:59 osmolarity of our urine and also reduce
16:02 the gfr to reduce the amount of water
16:04 that's getting excreted so diabetes
16:06 insipidus means dilute
16:08 urine due to inappropriate adh either
16:10 due to
16:11 reduced secretion and low levels in
16:14 central
16:15 or not responding to adh in the kidneys
16:17 which is nephrogenic
16:18 diabetes insipidus we do have syndrome
16:20 of inappropriate adh
16:22 siadh which means adh is getting
16:25 secreted from an anomalous site
16:27 like a cancer within the lungs this will
16:30 dilute our body fluids by
16:32 actually hyper concentrating our urine
16:34 because now adh is sucking all the water
16:37 out of our nephrons and that gets
16:38 treated by an
16:39 adh antagonist the last hormone we'll
16:42 talk about coming from the posterior
16:43 pituitary gland
16:44 is oxytocin which is the milk let down
16:47 hormone so prolactin
16:49 stimulates milk production oxytocin then
16:52 tells that milk to be let down or
16:54 ejected
16:55 so the stimulus for that is obviously
16:57 going to be suckling or we do have some
16:58 other stimulatory factors like the sight
17:00 sound or smell of an infant
17:02 and it is also released with dilation of
17:04 the cervix during pregnancy it actually
17:06 helps with uterine contractions this is
17:08 one of those positive feedback
17:10 mechanisms during pregnancy
17:12 it is inhibited from opioids but other
17:14 than that that'll conclude
17:16 our video for today in the next video
17:18 we'll go over
17:19 our thyroid hormones in our thyroid
17:21 gland feel free to drop a comment
17:23 otherwise we'll see in the next video
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