TBL2 Hypothalamus and Pituitary Gland Flashcards
Cells in the neurohypophysis include
- Nerve axons (cell bodies from the hypothalamus)
- Pituicytes (glial-like cells)
________ artery drains the neurohypophysis.
Inferior hypophyseal artery
With relevance to the neurohypohysis, there are two hypothalamic nuclei with cell bodies.
These magnocellular neurons pass through the pituitary stalk and terminate in the neurohypophysis.
- Paraventricular nucleus
2. Supraoptic nucleus
Paraventricular nuclei neurons can terminate at 3 places.
- Neurohypophysis (magnocellular)
- Median eminence (parvocellular) (primary capillary plexus which drains down into secondary capillary plexus through the portal veins => important for adenohypophysis)
- Other parts of the CNS
Presence of _______ in the magnocellular neurons that terminate in the _________
Herring bodies
terminates in the neurohypophysis
Vasopressin synthesis:
Pre-provasopressin that contains ________
=> Pre-prohormone that contains 3 domains
Pre-provasopressin
=> contains signal peptide
Pre-prohormone => contains Vasopressin (AVP), Neurophysin (NP) and Glycopeptide (GP)
Difference between vasopressin and oxytocin synthesis?
- Neurophysin differs slightly
2. Glycopeptide is absent in oxytocin
Vasopressin and oxytocin are made up of ___ amino acids each. (peptide hormone)
9 (6 in a ring)
Vasopressin and oxytocin are initially synthesised as ________, which are then cleaved to form hormones and their _______ proteins, as well as ________ that is also released.
- initially synthesised as prohormones
- cleaved to form hormones and their neurophysin proteins
- glycopeptide protein released for vasopressin as well (absent in oxytocin)
Principal physiological action of vasopressin (ADH) is acting on
principal cells of renal collecting ducts
- increases water reabsorption
- antidiuretic effect
Functions of vasopressin
- increase water reabsorption
- vasoconstriction of arterioles
- stimulates ACTH release (together with CRH)
- neurotransmitter (CNS effect)
- blood clotting factors synthesis (VIII and Von Willbrandt factor)
Vasopressin receptors
V1a
- vasoconstriction of arterioles
- glycogenolysis for hepatocytes
- CNS neurones
V1b (V3)
- ACTH release
V2
- renal water reabsorption
- blood clotting factors
Second messenger system of V1a and V1b receptors for vasopressin
(Gq/Gs/Gi)
- Gq
- linked via G proteins to Phospholipase C (PLC)
- which acts on membrane phospholipids to produce IP3 (inositol triphosphate) and DAG
- which increases cytoplasmic Ca2+ and other intracellular mediators (PKC) which produce cellular response
Second messenger system of V2 receptors (vasopressin)
Gs/Gi/Gq
Gs
- linked via G proteins to adenylyl cyclase, activating it
- forming cAMP
- activates PKA
- in turn activates other mediators to produce cellular response
(Aquaportins)
Vasopressin acts on ___ receptors present on principal cells of the collecting duct to produce ______ and increase water reabsorption.
V2 receptors
produce aquaporins 2
2 main Stimuli for vasopressin release
- Increased plasma osmolarity detected by osmoreceptors
2. Decreased arterial BP detected by baroreceptors
Osmoreceptors (which detect the changes in plasma osmolarity) needs to be in contact with both the circulating blood plasma and the brain.
Therefore, osmoreceptors are outside the ________ in order to be in contact with the blood. When osmoreceptors are stimulated, they will activate the vasopressinergic neurons in the hypothalamus which will secrete AVP to act on the principal cells of the collecting duct.
osmoreceptors must be present outside the blood-brain barrier.
2 main effects of oxytocin
- Breast during lactation => milk ejection
2. Uterus at parturition => delivery of baby
There are two types of diabetes insipidus.
- Central DI - no vasopressin produced
- Nephrogenic DI - tissue insensitivity to vasopressin
=> polyuria, polydipsia
Adenohypophysis is made up of _______ cells.
secretory cells
__________ is present in the median eminence and it receives blood from the superior hypophysial artery.
Second capillary plexus is present in the ________.
Primary capillary plexus
Anterior pituitary
Link between hypothalamus and the adenohypophysis is the __________.
hypothalamus-hypophyseal portal system
primary and secondary capillary plexus, portal veins
__________ capillaries (present in the primary capillary plexus) allows for the passage of molecules through the blood.
Fenestrated capillaries
(neurosecretions from the hypothalamus can pass through the capillary wall and enter the primary plexus to be transported to the secondary capillary plexus in the adenohypophysis through the portal veins)
The adenohypophysial hormones are stored in _________ and are cleaved to form the bioactive hormone and released by _________ when stimulated.
- stored in secretory granules
- released by exocytosis (Ca2+ regulated process)
Growth hormones and prolactin are ________ hormones.
protein hormones
TSH, LH and FSH are ________ hormones.
glycoprotein hormones
a subunit common to all; B subunit is unique
ACTH is a _______ hormone.
polypeptide hormone
- originates from POMC
Growth hormone (produced by adenohypophysis) is regulated by (hormone(s)) released from the hypothalamus.
- GHRH/somatotrophin releasing hormone
2. somatostatin (inhibitory)
Prolactin (produced by adenohypophysos) is regulated by which hormone released from hypothalamus?
- Dopamine (continually inhibitory)
2. Thyrotrophin releasing hormone (TRH)
Thyrotrophin (i.e. TSH produced by adenohypophysis) is regulated by _______ released from hypothalamus?
- TRH
LH and FSH are regulated by ______ and ______ produced by the hypothalamus.
- GnRH
2. GnIH
ACTH is regulated by _______ and _______ produced by the hypothalamus.
- CRH
2. Vasopressin (releasing)
Growth hormones (somatotrophins) work on general body tissues, particularly the _______.
liver
High prolactin levels will lead to:
- Reduced sexual behaviour
- Decreased LH release
- Increased LH receptors
Prolactin is under normal _________ by dopamine under normal circumstances.
normal inhibition by dopamine
=> to stimulate the release of prolactin when suckling occurs, there should be an inhibition of dopamine to reduce the inhibitory effect.
_________ and __________ also have effects on prolactin release.
oestrogen and iodothyronines
How to differentiate between DI patients and normal/polydipsic patients?
Fluid deprivation test for urine osmolality
DI patients will not show an increase in urine osmolarity despite fluid deprivation
How to differentiate between nephrogenic and central DI?
DDAVP administration
- central DI patients will show an increase in urine osmolality, whereas nephrogenic DI will not show any changes in urine osmolality.
The clinical condition where the plasma vasopressin concentration is inappropriate for the existing plasma osmolarity is known as ________.
SIADH
_______ is a peptidergic agonist for V1 receptor.
Terlipressin (arteriole effects)
- useful for oesophageal varices
________ is a peptidergic agonist for V2 receptor.
DDAVP desmopressin (renal effects)
- sustained decrease in urine flow
- sustained increase in urine osmolarity (AD effect)
_______ is used in the treatment of nephrogenic diabetes insipidus.
(no point administering vasopressin analogues due to insensitivity)
Thiazides
- inhibits Na+/Cl- transport across the distal tubule => reduces water reabsorption => diuretic effect
- compensatory increase in Na+ reabsorption in proximal tubule => increased proximal water reabsorption
=> decreased amount of fluid reaching collecting duct -> reduced urine volume
_______ is a non-peptide vasopressin analogue that is a V2 receptor antagonist for treatment of SIADH.
Tolvaptan
_______ (drug) stimulates vasopressin secretion.
Nicotine
Alcohol and ________ (drug) inhibits vasopressin secretion.
Alcohol and glucocorticoids inhibits vasopressin secretion.
________ refers to the decreased production of all anterior pituitary hormones.
Panhypopituitarism
After radiotherapy, there can be a progressive loss of pituitary secretion, often in the following order.
- LH/FSH
- GH
- TSH
- ACTH
- Prolactin
________ refers to the destruction of the anterior lobe of the pituitary gland, leading to panhypopituitarism.
Simmond’s disease
- insidious in onset
- caused by infiltrative processes, pituitary tumours, etc.
________ is a form of panhypopituitarism that is specific in women. It develops acutely following post-partum haemorrhage resulting in pituitary infarction.
Sheehan’s syndrome
__________ is an example of panhypopituitarism that results due to intra-pituitary haemorrhage. Often in patients with pre-existing pituitary tumours which suddenly infarct.
Pituitary apoplexy
Endocrine testing involves two main dynamic types.
- stimulation test - hypofunction
2. suppression test - hyperfunction
_______ tests involve the administration of exogenous trophic hormones (e.g. TRH/LHRH/ACTH) or stimulation of endogenous hormones (e.g. hypoglycemia stimulates GH and cortisol production)
Stimulation
The anterior pituitary is composed of _________ cells derived embryologically from the developing _______.
adenohypophysis
- epithelial secretory cells
- developed from the oral cavity Rathke’s pouch
Local mass effects of pituitary disease include:
- Bitemporal hemianopsia - visual field abnormalities due to the compression of the optic chiasma
- Elevated intracranial pressure
- Cranial nerve palsy
- Pituitary apoplexy (acute haemorrhage of the pituitary neoplasm)
The most common cause of hyperpituitarism is
hormone-producing adenoma arising in the anterior lobe
Pituitary adenomas can be
functional: hormone-producing
non-functional: not producing hormone
silent: hormone production at the tissue level, without clinical manifestations of hormone excess
Non-functioning pituitary adenomas are usually (macro/microadenomas).
macroadenomas
does not produce hormones => detected late => macroadenoma => destruct pituitary parenchyma => hypopituitarism
_________ mutations are one of the most common genomic alterations in pituitary adenomas.
G-protein mutations in the cell surface receptors (e.g. GHRH receptor)
Approximately 40% of __________ adenomas bear GNAS mutations. This abrogates the GTPase activity of Gsa, leading to a constitutively active Gsa, and unchecked cellular proliferation.
somatotroph cell adenomas
GNAS gene: encodes a-subunit of Gs protein
GNAS mutations are observed in 2 main types of pituitary adenomas.
- somatotrophs
2. corticotroph adenomas
_______ adenomas are the most common type of hyperfunctioning pituitary adenoma, followed by _______.
- Lactotroph adenomas (prolactin-secreting)
2. Somatotroph adenomas (GH)
Persistent GH excess stimulates the hepatic secretion of _________, which acts in conjunction with GH to induce overgrowth of bones and muscles.
GH excess can also lead to __________ by inducing insulin resistance.
IGF-1 (insulin-like growth factor 1)
GH excess => diabetes mellitus
Cushings syndrome
adrenal hypersecretion of cortisol
Nelson syndrome
- develops after the removal of adrenals as a treatment for Cushings
- due to the lack of negative feedback inhibitory effect of adrenal corticosteroids on corticotroph microadenoma
_____ synthesis accompanies that of ACTH, thus patients with Cushing syndrome often have hyperpigmented skin.
MSH (derived from the same precursor as ACTH)
Hypopituitarism occur mainly due to the
loss or absence of the anterior pituitary parenchyma
