hypothalamus-pituitary axis Flashcards
what are the different nuclei of the hypothalamus?
o PV – paraventricular o A – anterior o S – supraoptic o DM – dorsamedial o VM – ventromedial o ARC – arcuate o P – posterior o M – mamillary body
what does the hypothalamus regulate?
pituitary function, feeding (appetite and satiety), stress response, water balance, sleep-wake cycle, thermoregulation, emotions
where is the pituitary gland?
sits in the sella turcica of the sphenoid bone
surrounded by the cavernous sinus
what hormones does the anterior pituitary release and what do they act on?
o GH all tissues o TSH thyroid o LH and FSH testis and ovary o Prolactin breast o ACTH adrenal
what hormones does the posterior pituitary release and what do they act on?
o Oxytocin uterus
o ADH kidneys
what artery has capillaries in the median eminence?
supraphyseal artery
what artery do hormones from the posterior pituitary travel through?
inferior hypophyseal artery
what nerves would a pituitary tumour affect?
nerves II, IV, VI, V1 or V2
what can pituitary tumours cause?
pituitary gigantism and pituitary apoplexy
where does the anterior pituitary grow from?
ectoderm that grows from the roof of the mouth (Rathke’s pouch).
o Upwards movement from the oral cavity
where does the posterior pituitary grow from?
forms from the diencephalon of the brain
what regulates development?
transcription factors
what transcription factor is important in pituitary development?
Pit1
what does a missing/mutated Pit1 cause?
o Growth hormone – short
o TSH – lack of thyroid function (hypothyroidism)
o Prolactin – doesn’t give clinical relevance in young ages
• Causes; cretinism, mental retardation, severe dwarfism
what regulates the GH axis?
growth hormone releasing hormone from the hypothalamus
what regulates the TSH axis?
TSH hormone from the hypothalamus
what inhibits the TSH axis?
somatostatin
what does TSH stimulate?
the thyroid gland to make T3 and T4
what regulates the prolactin axis?
dopamine
what regulates the ACTH axis?
stimulated by CRH (hypothalamus) + AVP (posterior pituitary hormone)
what does kisspeptin do?
kisspeptin stimulates GnRH –> LH and FSH
describe what happens in primary underactivity
damage to the target organ (e.g. thyroid organ is taken out or an autoimmune response attacks it).
o Increased pituitary + hypothalamus hormone but decreased target hormone.
o Defect of the thyroid organs
o Patient with high prolactin should have thyroid tested
describe what happens in secondary underactivity?
pituitary damage problem stimulating target organ.
o Increased hypothalamus stimulatory hormone, decreased pituitary (appears normal – lower range) and target hormone
explain primary overactivity
o Too much target hormone which decreases pituitary hormone and decreases the hypothalamic stimulatory hormone
give examples of causes of primary overactivity
e.g. thyroid toxic nodule or adrenal tumour making too much cortisol
explain secondary overactivity
Pituitary tumour makes too much pituitary hormone
o Target organ grows
o More target hormone more pituitary hormone less hypothalamus stimulatory hormone
what stimulates GH?
GHRH and ghrelin
what inhibits GH?
somatostatin
what does GH stimulate?
insulin-like growth factor production
what does IGF stimulate and inhibit?
o Inhibits GF and GFHRH via negative feedback.
o Stimulates secretion of SS.
what can a GHRH receptor mutation cause?
dwarfism
what is acromegaly?
too much growth hormone
how is acromegaly?
treated with mutant GH molecule that can only bind one part of the receptor. Acts as a competitive inhibitor.
what are the roles of GHRH?
- Stimulatory hormone
- Promotes GH cell clusters for coordinated responses between GH cells
- Increase GH cell number – Not enough GHRH = small pituitary
- Increase GH synthesis by activating Pit1 transcription factor
- Stimulates GH release.
what type of receptor is the GHRH receptor?
GPCR
explain how a GPCR reacts when a hormone binds
- When a hormone binds to the receptor, alpha subunit binds the receptor.
- At the same time, GDP attached to the alpha subunit is phosphorylated to GTP
- Alpha subunit dissociates from the G protein and binds to AC – activated and makes cAMP
- cAMP activity is increased increases PKA levels
- Cellular response
what is the Gsp oncogene and what conditions is it seen in?
mutate alpha subunit which cannot hydrolyse GTP to GDP constant activation of AC
o Seen in 40% of somatotroph tumours (people with acromegaly)
what causes mccune albright syndrome?
• Mosaic mutation in GNAS gene – not inherited
o R201 mutation
• Spontaneous mutation in the embryo.
o Prevents downregulation of cAMP in GCPRs
what does mccune-albright syndrome result in?
o Acromegaly o Fibrous dysplasia o Hyper functioning endocrine organs (hyperthyroid goitre) o Precocious puberty (GnRH-independent) o Hyperthyroid goitre o Adrenal hyperplasia o Somatotroph hyperplasia o Bone deformities. o Skin discolorations (often to café au lait color).
which gender is mccune-albright syndrome more common in?
females
how many receptors can somatostatin act on?
5
what does ACTH do?
• ACTH stimulates cortisol production from the adrenal gland.
o Inhibits CRH, ADH, ACTH via negative feedback.
what causes Cushing’s disease
too much cortisol
what causes Addison’s disease
too little cortisol
describe the circadian rhythm of cortisol
- Pulsatile secretion like growth hormone
- Undetectable levels during the night
- Levels start to rise at about 3am.
- Peak in the morning between 6-9am.
- Levels decline throughout the day.
what happens to cortisol levels when you have disrupted sleep?
cortisol levels get high
what are the 2 types of cushings syndrome?
ACTH independent
ACT dependent
what is the most common cause of ACTH independent Cushings syndrome?
steroid therapy
adrenal tumour may be the cause
what are the ACTH levels like in ACTH dependent Cushings syndrome?
Levels are raised primarily
what are the symptoms of cushings syndrome?
o Weight gain, muscle weakness and skin changes.
