Pituitary and hypothalamic physiology
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What are the players in the hypothalamus-pituitary unit?
- Hypothalamus: Anatomic subset of CNS neurons
- Anterior pituitary (adenohypophysis): Epithelial origin, arising from roof of mouth (Rathke’s pouch)
- Posterior pituitary (neurohypophysis): Neural origin. These are actually cells of the CNS whose axons extend down to meet the cells of the anterior pituitary. The bundle of axons = pituitary stalk
What is known as the master regulator/ or central control gland and what dies it do in general terms?
- The pituitary is a central control gland affecting the function of many downstream endocrine glands
- It takes input from higher centers via the hypothalamus
- It provides input to target glands via endocrine signaling
- However, rather than a single gland, it functions more like a central location where many pathways cross, but interact only minimally
How does the pituitary develop? Like what structures does it come from.. Come on woman you know this!!
- anterior pituitary comes from the oral ectoderm. The rathke pouch is made and that is what makes the anterior pituitary
- posterior pituitary comes from the brain tissue mesoderm a mandibular process is made that makes the posterior pituitary
Explain anatomically where the pituitary is located?
- Pituitary sits in the sella turcica (below the sella turcica are the sphenoid sinuses)
- to either side are the cavernous sinus along with the carotid artery
- optic chiasm crosses over the top of the pituitary gland
So what are the cell types that make up the anterior pituitary and what are the hormones that they secrete?
- Cell type-------Hormone--------Stimulates
- Corticotroph- ACTH- Adrenals
- Thyrotrophs- TSH- Thyroid
- Lactotrophs- Prolactin- mammary
- Gonadotrophs- LH/FSH- gonads
- Somatotrophs- GH- Liver and others
So how are the pituitary hormones made?
So all of them start off as a single precursor cell that expresses Rpx.
What is the overall function of the H-P-x system?
the hypothalamus is an anatomical subset of the CNS which provides the integration for higher order signals from the brain to the endocrine system and these signals are passed locally to the anterior pituitary gland which relays the signal in endocrine fashion to target endocrine glands distributed throughout the body. However, each of these systems functions more or less independently of the others.
So the hypothalamus is important, like i get it but how does it know what to do?
Well funny you would ask, it receives neural and hormonal input from multiple sources.
Explain the whole feedback loop system.
- Ok so do you want to know about the short or the long feedback loop? In either case I will explain both.. HA!! Bc I am THAT good!!!
- Short FB loop: when gland A secretes a hormone which works on gland B and the product of gland B goes back and directly feedbacks on gland A.
- Long FB loop: when hormone produces feedback but not directly on the gland that it stimulates it..
- Also it is important to note that a hormone can function as both a long and a short feedback loop.
So how does the hypothalamus release its hormone and how does it get from point A to B??
Wellllllllllllllllllll, ok.. So the hypothalamus releases hormones into the portal system to the pituitary but only those that have the appropriate receptors will respond.. so that is how specificity is achieved.
How many HPx systems are there.
- 3.. well that we know of ya know..
- HP- adrenal
- HP- gonad
- HP- thyroid
- but there are other HP effector systems that are not as clearly defined such as the: growth hormone axis, prolactin axis and the posterior pituitary (i know we hardly talk about that guy)
So hypothalmic hormones.. GO!!! (OMG really do I need to do everything around here?!!? What are they, how are they secreted, what do they do etc woman!!!)
- Gosh so moody!! Ok
- most are small peptides so they are rapidly degraded in serum which makes their measurement super tricky.. Add to that that they are secreted in pulsatile fashion and pretty much a random blood test is like pointless.
- Cool thing is that they can regulate their own release through a short FB loop..
- These hypothalamic hormones stimulate the release and synthesis of anterior pituitary hormones and they also stimulate the growth of anterior pituitary cells. So if there is some hypothalamic hormone missing then that can cause the atrophy of the cells...
- WHEW!! That was a lot!
Hypophysiotropic hormones.. What are they? What do they do?
- They are the hormones secreted by the hypothalamus..
- So here we go..
So we have this patient.. Lets call him Joe that needs to have their pituitary function evaluated.. How do we do this?
Ok so by now I hope you know that a simple blood test is not enough... why? think about it..... ok so hopefully you got this by yourself but if you didn't its bc the pituitary hormones are highly dynamic so random measurements may not provide a good evaluation of function so we NEED to target hormone levels to also be measured if not the pituitary hormone function CANNOT BE EVALUATED.. I will repeat.. Pituitary hormone function can't be evaluated unless target hormone levels are also measured... So in order to assess pituitary function, testing typically relies on exogenously stimulating or suppressing the pituitary gland to make sure that its behaving normally..
Explain the HPA and the feedback regulation.
So Cortisol is the only one involved with short and long loop FB.. Although ACTH causes secretion of DHEA an Aldosterone also these do not provide negative FB to the axis.
So... CRH what is it? Where is it secreted from? half life? what does it do? what stimulates it? what inhibits it?
- Gosh so many questions.. Ok
- What is it?: it is an aa peptide secreted from the hypothalamus
- half-life: long like 1 hr
- What does it do?: It stimulates secretion of ACTH from corticotrophs
- Stimulated by: ADH and angiotensin 2 and also by neural inputs and stress
- Inhibited by: Cortisol and oxytosin
ACTH what is it? Where is it secreted from? what does it do? what inhibits it? Precursor? fun fact?
- Gosh so many questions.. Ok
- Secreted by: corticotrophs of the anterior pituitary in response to CRH
- Precursor: POMC
- What does it do?: stimulates the secretion of cotisol and sex steroids from the adrenal glands and it also stimulates growth of the adrenal cortex.
- It inhibits: CRH release
- Fun fact: It has a diurnal pattern and it is usually highest earliest in the morning
So lets say hypothetically that I have a bunch of POMC around.. First of all what the heck is this and what can it do?
Ok so POMC is a pre-hormone which has ACTH and also gamma and beta MSH and there are also endorphins and enkephalins.. So ok if you have high levels of ACTH this can cause increased release of cortisol, aldosterone, and DHEA.. Also because it has gamma and beta (and alpha also) MSH then the patient will also have excess pigmentation by stimulation of the melanocortin receptors.
So adrenal steroids.. What are they stimulated by? and what is it responsible for?
- So ACTH stimulated the pxn of cortisol form the adrenal cortex and in fact, the pxn of all adrenal steroids is stimulated by ACTH.
- Cortisol is responsible for negative feedback to pituitary and adrenal
So HPG axis explain it... NOW!! GO!!
So as you see here well you see it.. no need to explain.
GnRH.. AKA? What does it do? What inhibits it? Fun fact?
- So it is also known as: LHRH
- it stimulates: LH and FSH from gonadotrphs but the regulation of FSH and LH release depends on the frequency and concentration of GnRH
- -- pulsatile secretion- LH/FSH is released
- -- continuous secretion- NO LH/FSH is released NONE! So when GnRH is secreted continuously it causes suppression of LH/FSH release and gonadal steroidogenesis
- inhibited by: sex hormones and prolactin
- Fun fact: its secretion differs in relation to the life cycle..
So there is a patient that has a small problem there is continuous release of GnRH.. What happens?
Small problem is the understatement of the century.. So this patient will have ni secretion of FSH/LH because GnRH is supposed to be released in a pulsatile form not continuous!!
Gonadotrophins.. What are they? when are they secreted? Fun fact...
- What are they?: LH, and FSH (TSH here for completeness but doesn't really have anything else to do here.. you know like that weird family member)
- Secreted by: gonadotrophs in response to GnRH
- Fun fact: ok.. you have a weird view of fun... So alpha subunits are identical it is the beta subunit which gives it its signaling specificity..
So what do sex steroids and inhibin do?
- Ok so super general..
- LH: this stimulates sex steriodogenesis ya know estrogen, progesterone and testosterone.
- LH stimulated Leydig cells in male and theca cells in female (I know like why couldn't leydig be female idk.. Scientist and making things complicated) And of course, women are more complicated because its not like boom LH and then we get estrogen.. Nope
What would you like to do?
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