Pituitary

Question 1

What are possible causes of disease?

Answer 1

VITAMIN CDEF Vascular Inflammation/Infection Trauma Auto-Immune Metabolic Iatrogenic/Idiopathic (doctor-causing/unknown) Neoplastic Congenital Degenerative Endocrine/Environmental Functional (means psychological)

Question 2

Where is the pituitary gland found?

Answer 2

Below the Hypothalamus.

Question 3

What surrounds the pituitary gland?

Answer 3

Sella Turcica (a bony-like saddle).

Question 4

What is the structure of the pituitary gland? (x2 names for each)

Answer 4

Anterior lobe (Adenohypophysis) Posterior lobe (Neurohypophysis)

Question 5

What is the anatomical difference between the adenohypophysis and neurohypophysis? (x2)

Answer 5

Adeno: secretory, needs a circulation, grown up embryonically from the roof of the mouth (different tissue of origin) i.e. dorsal growth of buccal activity. The differentiated cells contain secretory granules. Neuro: does not require circulation in the same respect to carry out function. grown down embryonically from neural tissue. i.e. ventral growth from the developing hypothalamus.

Question 6

What is the structure of the anterior pituitary?

Answer 6

Hypothalamic nuclei: are a collection of neuronal cell bodies – each ‘nuclei’ describe specific functions. Pars tuberalis: surrounds the pituitary stalk with a highly vascularized sheath. Pars distalis: the major secretor section of the anterior pituitary lobe. Region of median eminence: one of the seven areas of the brain devoid of a blood–brain barrier, so can communication directly with blood circulation.

Question 7

How is the hypothalamic-hypophysial portal circulation structured? Why does it have it?

Answer 7

Circulation required to transport the hormones directly from the pituitary to the rest of the body. Median Eminence 2nd capillary bed found in anterior lobe. fenestrations allows for neurosecretions to enter blood stream and get into pituitary.

Question 8

How is the circulation in the anterior lobe supplied?

Answer 8

Circulation supplied by the superior hypophysial artery.

Question 9

Through what does the circulation in the anterior lobe leave? (x2 parts of the anatomy)

Answer 9

Goes out past the Cavernous sinus via jugular veins.

Question 10

How is the anterior lobe of the pituitary gland regulated?

Answer 10

Regulated by the hypothalamus immediately above.

Question 11

How does the hypothalamus communicate with the anterior pituitary gland?

Answer 11

Hypothalamic nuclei produce neuro-secretions (the name given to its hormones), which are pumped out into the axon. Some of these axons terminate at the primary capillary plexus at the median eminence. It is here that the neuro-secretions travel down the axon and enter circulation.

Question 12

Describe the mechanism of anterior pituitary gland secretion, including the mechanism that the hypothalamus controls it.

Answer 12

1. HYPOTHALAMIC NEUROSECRETION: Neuro-secretions are released into hypothalamo-hypophysial portal system. They are taken up by the primary capillary plexus through its fenestrations. 2. Hormones travel in the blood down the long portal veins to the secondary capillary plexus (found in anterior lobe). 3. HYPOTHALAMIC NEUROSECRETION: Some of the hormone leaks out of the secondary capillary plexus where they influence the anterior pituitary gland. 4. Relevant pituitary cell RELEASES ITS ADENOHYPOPHYSIAL HORMONE into general circulation.

Question 13

What are the hypothalamic nuclei?

Answer 13

Collection of neuronal cell bodies in the hypothalamus! OF Hypothalamic neurones.

Question 14

What is the mechanism of anterior pituitary secretion and hypothalamus control called?

Answer 14

Hypothalamo-adenohypophysial axis.

Question 15

What are the five cell types in the anterior pituitary gland?

Answer 15

SOMATOTROPHS LACTOTROPHS THYROTROPHS GONADOTROPHS CORTICOTOPHS

Question 16

What are the 6 hormones secreted by the anterior pituitary gland (and their cell type)?

Answer 16

SOMATOTROPHS: GROWTH HORMONE (also known as Somatotrophin) LACTOTROPHS: Prolactin THYROTROPHS: Thyroid Stimulating Hormone (TSH, aka Thyrotrophin) GONADOTROPHS: Luteinising Hormone (LH) AND Follicle Stimulating Hormone (FSH) CORTICOTOPHS: Adrenocorticotrophic hormone (ACTH, aka Corticotrophin)

Question 17

How are the adenohypophysial hormones generally produced for secretion by pituitary?

Answer 17

1. PRECURSOR molecule called Prohormones. 2. Enzymatic cleavage of prohormone to yield the bioactive hormone molecule. 3. Adenohypophysial hormones stored in secretory granules. 4. Released by exocytosis.

Question 18

Example of Corticotrophin (ACTH) (in relation to synthesis from prohormone)? How is it synthesised (this is an anterior pituitary gland hormone)?

Answer 18

Prohormone = POMC (ProOpioMelanoCorticotrophin).
After enzyme cleavage = CORTICOTROPHIN + Pro-yMSH + βLPH.

Question 19

How large are each of the anterior hormones and what category do they fit into (Proteins, glycoproteins, polypeptide)?

Answer 19

[NOT NEEDED AS KNOWLEDGE – BUT WASN’T SURE ABOUT LEAVING IT OUT EITHER]. PROTEIN: Growth hormone 191aa Prolactin 199aa GLYCOPROTEINS: consisting of an alpha and beta subunit (92aa alpha common to both) TSH: beta-subunit 110aa LH and FSH: beta-subunit for both = 115aa POLYPEPTIDE: ACTH 39aa

Question 20

List the hypothalamic hormones for each adenopophyseal hormone. (x2, x2, x1, x1, x2)

Answer 20

Somatotrophin: Growth Hormone Releasing Hormone (GHRH) STIMULATES Somatostatin (SS) INHIBITS (somatostatin isn’t produced in the pituitary, it’s produced in the hypothalamus. Growth Hormone therefore has an on/off switch. Prolactin: only hormone that’s under negative control i.e. it’s being inhibited all the time. DOPAMINE: Prolactin increases when dopamine levels fall. Thyrotrophin releasing hormone: also helps increase prolactin but much less significant. Thyroid Stimulating Hormone: Thyrotropin releasing hormone (TRH). LH and FSH: Gonadotrophin releasing hormone (GnRH) ACTH: Corticotrophin releasing hormone (CRH – main one) and Vasopressin (SOME stimulation).

Question 21

What does each of the anterior pituitary gland’s hormones do?

Answer 21

GROWTH HORMONE: Affects all body tissues. Stimulates growth, cell reproduction, and cell regeneration, particularly in the liver. Impacts children most – obviously. PROLACTIN: enables females to lactate (affects breasts) THYROTOPHIN: stimulates thyroid hormone secretion. GONADTROPHINS (LH and FSH): stimulates testosterone and sperm production respectively. Involved in the menstrual cycle. Acts therefore, on the testes and ovaries. CORTICOTROPHIN: regulates certain adrenal gland secretion and affects the adrenal CORTEX.

Question 22

How does the feedback loop operate in the action of Prolactin and Dopamine? How is the feedback loop labelled? (x2) What is the loop called?

Answer 22

Dopamine suppresses prolactin. Small levels of prolactin allows for some lactation. Suckling = neuronal response transmitted to the dopaminergic neurones in the brain = less dopamine = more prolactin = more milk. Action of prolactin on the breast is an example of the EFFERENT ENDOCRINE PATHWAY in the feedback loop, and the breast’s response is an example of AFFERENT NEURAL PATHWAY. Feedback loop is called the neuro-endocrine reflex arc.

Question 23

How does the actions of Growth Hormone become apparent? (x2 ways)

Answer 23

DIRECTLY: binding to receptors on bone and muscle for example. INDIRECTLY: binds to receptors on liver and tells it to make IGF I (and IGF II) which are Somatomedins (growth mediators). Skeletal and muscle tissue (as examples) will have IGF I (and IGF II) RECEPTORS, which respond to these mediators with growth and development.

Question 24

What are the effects of the growth hormone? (x5, x2 pathological).

Answer 24

Stimulate protein synthesis. Increase glucose production (can develop diabetes). Stimulates fat breakdown. Increase cartilaginous and bone growth. All this growth can predispose to malignancy in excess.

Question 25

What affects the secretion of GHRH/Somatostatin in the hypothalamus? (x6) Hypoglycaemia in detail.

Answer 25

ALL THAT ARE LISTED STIMULATES GHRH (which then means more Growth Hormone). Certain amino acids e.g. arginine, fasting (induces hypoglycaemia), exercise, oestrogens, stress, sleep. Hypoglycaemia (in a study) would be induced by injecting insulin. Stress on body = surge in growth hormone.

Question 26

What affects the secretion of Growth Hormone? (x2)

Answer 26

Hypothalamus – GHRH and SS. Ghrelin (hormone from stomach) increase Growth Hormone.

Question 27

What is the structure of the posterior pituitary gland, including hypothalamus? (and differences with anterior pituitary)

Answer 27

Hypothalamic neurones extend across median eminence, directly to the posterior gland. In anterior system, hormones reach destination via the hypophyseal portal vessel. LEARN THE VESSEL NAMES FOR EACH!

Question 28

How does communication between the hypothalamus and posterior pituitary work? Difference with anterior?

Answer 28

Don’t secrete hormones into median eminence (which moves into anterior). Neuro-secretions are instead released directly into the posterior pituitary blood supply because neurones project to the posterior.

Question 29

Where are the cell bodies (hypothalamic nuclei) for the neurones that interact with the anterior and posterior pituitary found? (x2)

Answer 29

Different parts of the hypothalamus. Originate in supraoptic (just posterior) and paraventricular nuclei (posterior and anterior).

Question 30

What are the names of the neurones that interact with the posterior pituitary? Describe them.

Answer 30

They are MAGNOCELLULAR neurones. Magnocellular neurones originate in the paraventricular OR supraoptic nuclei, and characterised by termination in the neurohypophysis. • Cell body (or the nuclei) contains machinery for posterior pituitary hormone production e.g. vasopressin/oxytocin. • These hormones move down the axon and are stored in Herring bodies. • They can travel down the axon to posterior pituitary where they are released into circulation.

Question 31

What is the name of the neurones that interact with the anterior pituitary? Describe it.

Answer 31

Parvocellular neurones. Originate in the paraventricular nuclei. Terminate in the median eminence or in other parts of the brain.

Question 32

What are supraoptic neurones and how do they work?

Answer 32

Supraoptic neurones leave supraoptic nuclei, pass through median eminence, and have Herring bodies across the axon. The neurones are all magnocellular.

Question 33

What are the sub-types of magnocellular neurones?

Answer 33

Sub-type named by the hormone it secretes. VASOPRESSINERGIC or OXYTOCINERGIC.

Question 34

What are paraventricular neurones and how do they work? Sub-types? (x3)

Answer 34

Paraventricular neurones originate in paraventricular nuclei.

Magnocellular AND parvocellular neurones extend from these nuclei (unlike just magnocellular in the supraoptic nuclei).

• Majority are magnocellular and pass down to the neurohypophysis i.e. hormones secreted in cell body, stored in Herring bodies, secreted at termination.
• Parvocellular neurones pass to other parts of the brain OR neurones terminate in the median eminence and affect the anterior pituitary.
• For all, sub-types are either VASOPRESSINIERGIC or OXYTOCINERGIC plus more depending on the hormone it releases.

Question 35

This is not a question, just an example of how the hypothalamic nuclei work for greater understanding.

Answer 35

Paraventricular neurones to the median eminence secrete either Vasopressin or CRH. They are released at the same time, at the same location (median eminence), and they pass down the portal system to the anterior pituitary. However, they go down separate neurones to get to the median eminence.

Question 36

What is Vasopressin also called?

Answer 36

ADH or AGV (arginine vasopressin)

Question 37

What hormones are secreted by the posterior pituitary gland? (x2)

Answer 37

Vasopressin Oxytocin

Question 38

How do the two posterior hormones differ in chemical structure? (x3 points). What do structural differences mean for function?

Answer 38

Peptides of 9 amino acids. Both have disulphide link which hold structure together. Differ by two amino acids, highlighted in red. Means that Oxytocin and Vasopressin can mimic some of its effects because of structural similarity, even though there are different receptors for these both hormones.

Question 39

How is Vasopressin synthesised? What are the pre- and pro- bits made of?

Answer 39

WHAT THEY ARE MADE OF – LOOK AT PHOTO

Most hormones begin as prohormones. Vasopressin begins as a pre-provasopressin – transcribed in the nucleus. SP (signal peptide) directs pre-prohormone where it needs to go. Lost once directed towards the axon. Now it is a prohormone. Provasopressin passes down the axon to the end of the neurone. It is kept as a prohormone because neurophysin maintains Vasopressin’s stability while it is stored in the Herrings body. Otherwise, might diffuse out of the body and neurone where it can be degraded by enzymes. At end of neurone, it gets cleaved to the active hormone. Neurophysin also secreted into blood stream. We don’t know what glycopeptide does.

Question 40

How does Oxytocin differ in its synthesis? (x2)

Answer 40

SAME MECHANISM AS VASOPRESSIN. Neurophysin differs slightly. Glycopeptide is absent.

Question 41

What are the two major receptors for vasopressin?

Answer 41

V1 and V2 receptors.

Question 42

What is the mechanism of action of V1 receptors?

Answer 42

V1 receptors linked via G proteins to phospholipase C which acts on membrane phospholipids to produce IP3. This increases cytoplasmic Ca2+ concentration and other intracellular mediators (PKC) – Ca2+ is a second messenger system.

Question 43

What is the mechanism of action of V2 receptors?

Answer 43

!!!

Question 44

What are the effects of each receptor of Vasopressin (and therefore Vasopressin) (x3, x1, x1).

Answer 44

V1a: Arterial smooth muscle – vasoconstriction, glycogenolysis in hepatocytes, and behavioural effects from CNS neurones. V1b: corticotrophs to increase ACTH production. V2: collecting duct cells – increase water reabsorption.

Question 45

What is the water reabsorption effect called?

Answer 45

Antidiuretic effect.

Question 46

What does vasopressin translate to?

Answer 46

Constriction of vessels.

Question 47

Describe what happens physiologically for the effects of increased water absorption to occur i.e. after receptor stimulation.

Answer 47

Aquaporins e have already been produced and are stored in aggraphores on the side of the tubule cell in contact with the basolateral membrane (in contact with blood side). Receptor stimulation upregulates aquaporin stimulation and movement of aggraphores to the apical membrane (lumen side), and AQP2 molecules inserted into membrane. So water moves across cell into blood plasma. AQP 3 and AQP 4 are found on the basolateral side which allows movement of water into blood plasma – not affected in the same way.

Question 48

What are the effects of oxytocin? (x2 classes, x3 for each)

Answer 48

Major – therapeutic effects: Uterus contraction during delivery. Effects myometrial cells. Therefore induces labour. Mammary gland – myoepithelial cells produce milk so oxytocin causes these cells to contract which promotes milk ejection. Minor – unwanted effects: because so like Vasopressin: Cardiovascular system – vasoconstriction. Important as this affects umbilical arteries and veins which helps transition between baby relying on unbilical chord and not when born. Increase water absorption. Both not as effectively as water absorption. CNS – maternal behaviour e.g. protect child and social interaction to seek out support. “Tend and befriend”. This doesn’t happen in men because testosterone inhibits oxytocin so behaviour not particularly exhibited.

Question 49

What does oxytocin do which results in uterus contraction? (x3)

Answer 49

Promotes rhythmic contraction. Increased cyclooxygenase production which increases prostaglandins. Prostaglandins break down collagen that keeps baby in-utero. Dilates cervix.

Question 50

What hormones does oxytocin work with? (x2 + x1)

Answer 50

Oestrogen enhances. Progesterone suppresses. (Testosterone suppresses.)

Question 51

When is uterus sensitive to oxytocin?

Answer 51

Towards end of pregnancy because of increased oestrogen levels which up-regulates oxytocin receptor synthesis.

Question 52

How is vasopressin controlled? (x2)

Answer 52

OSMOLALITY:
If plasma osmolality goes up (increased salt) – osmolality higher in blood than osmoreceptors in the hypothalamus – fluid therefore leaves the osmoreceptors which results in shrinkage – this stimulates neurone to fire and activates vasopressin secretion from neurones at the posterior pituitary.
Vasopressin in the kidney promotes water reabsorption, so plasma osmolality goes down.

BLOOD PRESSURE:
Blood pressure falls – baroreceptors around the body are stimulated by increased BP, so fire rate of receptors goes down – results in inhibitory effect on Vasopressin which results in INCREASED VASOCONSTRICTION, increases the resistance in the cardiovascular system which results in increased BP.

Question 53

Why are there two mechanisms of controlling vasopressin levels?

Answer 53

Because vasopressin has two effects.

Question 54

How is oxytocin controlled? Using example of suckling baby.

Answer 54

Neuroendocrine reflex arc mechanism (endocrine effect stimulated by an afferent nerve, and efferent nerves INDEPENDENT OF THE BRAIN (hence reflex arc) delivering a response). Babies start suckling. Nerves around nipples stimulates afferent neurones. Stimulates direct (because avoids brain) efferent effect which leads to oxytocin production. Released in the posterior pituitary and acts on myoepithelial cell in breast (REFLEX) = milk ejection.

Question 55

What happens when each neuropophysial hormones is lacking?

Answer 55

OXYTOCIN: not a major issue. Can be replaced by other hormones e.g. vasopressin mimics. VASOPRESSION: leads to diabetes insipidus. Not actually diabetes but named this way because has similar symptoms and back in the old days, they couldn’t make the differentiation e.g. drinks lots of water (polydipsia, polyuria and urine very dilute).

Question 56

What happens when too much vasopressin?

Answer 56

Syndrome of inappropriate ADH. E.g. this occurs in tumours.

Question 57

What are the two types of diabetes insipidus?

Answer 57

Central (or CRANIAL) and NEPHROGENIC.

Question 58

What is cranial diabetes insipidus?

Answer 58

When vasopressin is not being produced by the pituitary.

Question 59

What is nephrogenic insipidus?

Answer 59

Can produce vasopressin but the kidneys and end organs don’t respond to it very well.

Question 60

What is cause of central diabetes insipidus? (x3)

Answer 60

Some tumours. Head trauma. Auto-immune destruction of the neurones.

Question 61

What is the cause of nephrogenic diabetes insipidus? (x1)

Answer 61

Drug induced which reduces kidney sensitivity.

Question 62

How can you differentiate between cranial and nephrogenic diabetes insipidus clinically?

Answer 62

Patient can be given ADH (Vasopressin) exogenously. If patient responds to this, patient has cranial diabetes insipidus. If patient doesn’t respond, there’s a problem with the kidney recognising it, and the patient has nephrogenic diabetes insipidus (HARDER TO TREAT because cranial can be treated by ADH administration).

Question 63

What happens with diabetes insipidus and why do you get the symptoms?

Answer 63

AS NORMAL: Dehydrated – plasma osmolality goes up, more vasopressin produced. BUT, kidneys do not respond or brain does not secrete/produce it. Means there’s no endocrine response and no water reabsorption. So, can be very dangerous. Increased osmolality also stimulates thirst, hence thirst symptoms – but means getting up in the night.

Question 64

What may be the endocrinological causes of short stature? (x6)

Answer 64

Growth Hormone deficiency Growth Hormone receptor recognition Lack of thyroid hormone Testosterone (but need to consider age) Excess steroid production (Cushing’s Syndrome) Vitamin D deficiency.

Question 65

Do hormones have only one specific receptor?

Answer 65

Not in all cases. Some have many specific receptors – this allows them to have wide ranging effects.