hypothalamus-pituitary axis

Question 1

what are the different nuclei of the hypothalamus?

Answer 1

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

Question 2

what does the hypothalamus regulate?

Answer 2

pituitary function, feeding (appetite and satiety), stress response, water balance, sleep-wake cycle, thermoregulation, emotions

Question 3

where is the pituitary gland?

Answer 3

sits in the sella turcica of the sphenoid bone

surrounded by the cavernous sinus

Question 4

what hormones does the anterior pituitary release and what do they act on?

Answer 4

o	GH  all tissues
o	TSH  thyroid
o	LH and FSH  testis and ovary
o	Prolactin  breast
o	ACTH  adrenal

Question 5

what hormones does the posterior pituitary release and what do they act on?

Answer 5

o Oxytocin  uterus

o ADH  kidneys

Question 6

what artery has capillaries in the median eminence?

Answer 6

supraphyseal artery

Question 7

what artery do hormones from the posterior pituitary travel through?

Answer 7

inferior hypophyseal artery

Question 8

what nerves would a pituitary tumour affect?

Answer 8

nerves II, IV, VI, V1 or V2

Question 9

what can pituitary tumours cause?

Answer 9

pituitary gigantism and pituitary apoplexy

Question 10

where does the anterior pituitary grow from?

Answer 10

ectoderm that grows from the roof of the mouth (Rathke’s pouch).
o Upwards movement from the oral cavity

Question 11

where does the posterior pituitary grow from?

Answer 11

forms from the diencephalon of the brain

Question 12

what regulates development?

Answer 12

transcription factors

Question 13

what transcription factor is important in pituitary development?

Answer 13

Pit1

Question 14

what does a missing/mutated Pit1 cause?

Answer 14

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

Question 15

what regulates the GH axis?

Answer 15

growth hormone releasing hormone from the hypothalamus

Question 16

what regulates the TSH axis?

Answer 16

TSH hormone from the hypothalamus

Question 17

what inhibits the TSH axis?

Answer 17

somatostatin

Question 18

what does TSH stimulate?

Answer 18

the thyroid gland to make T3 and T4

Question 19

what regulates the prolactin axis?

Answer 19

dopamine

Question 20

what regulates the ACTH axis?

Answer 20

stimulated by CRH (hypothalamus) + AVP (posterior pituitary hormone)

Question 21

what does kisspeptin do?

Answer 21

kisspeptin stimulates GnRH –> LH and FSH

Question 22

describe what happens in primary underactivity

Answer 22

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

Question 23

describe what happens in secondary underactivity?

Answer 23

pituitary damage  problem stimulating target organ.

o Increased hypothalamus stimulatory hormone, decreased pituitary (appears normal – lower range) and target hormone

Question 24

explain primary overactivity

Answer 24

o Too much target hormone which decreases pituitary hormone and decreases the hypothalamic stimulatory hormone

Question 25

give examples of causes of primary overactivity

Answer 25

e.g. thyroid toxic nodule or adrenal tumour making too much cortisol

Question 26

explain secondary overactivity

Answer 26

Pituitary tumour makes too much pituitary hormone o Target organ grows o More target hormone  more pituitary hormone  less hypothalamus stimulatory hormone

Question 27

what stimulates GH?

Answer 27

GHRH and ghrelin

Question 28

what inhibits GH?

Answer 28

somatostatin

Question 29

what does GH stimulate?

Answer 29

insulin-like growth factor production

Question 30

what does IGF stimulate and inhibit?

Answer 30

o Inhibits GF and GFHRH via negative feedback. | o Stimulates secretion of SS.

Question 31

what can a GHRH receptor mutation cause?

Answer 31

dwarfism

Question 32

what is acromegaly?

Answer 32

too much growth hormone

Question 33

how is acromegaly?

Answer 33

treated with mutant GH molecule that can only bind one part of the receptor. Acts as a competitive inhibitor.

Question 34

what are the roles of GHRH?

Answer 34

* 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.

Question 35

what type of receptor is the GHRH receptor?

Answer 35

GPCR

Question 36

explain how a GPCR reacts when a hormone binds

Answer 36

* 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

Question 37

what is the Gsp oncogene and what conditions is it seen in?

Answer 37

mutate alpha subunit which cannot hydrolyse GTP to GDP  constant activation of AC o Seen in 40% of somatotroph tumours (people with acromegaly)

Question 38

what causes mccune albright syndrome?

Answer 38

• Mosaic mutation in GNAS gene – not inherited o R201 mutation • Spontaneous mutation in the embryo. o Prevents downregulation of cAMP in GCPRs

Question 39

what does mccune-albright syndrome result in?

Answer 39

``` 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). ```

Question 40

which gender is mccune-albright syndrome more common in?

Answer 40

females

Question 41

how many receptors can somatostatin act on?

Answer 41

5

Question 42

what does ACTH do?

Answer 42

• ACTH stimulates cortisol production from the adrenal gland. o Inhibits CRH, ADH, ACTH via negative feedback.

Question 43

what causes Cushing's disease

Answer 43

too much cortisol

Question 44

what causes Addison's disease

Answer 44

too little cortisol

Question 45

describe the circadian rhythm of cortisol

Answer 45

* 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.

Question 46

what happens to cortisol levels when you have disrupted sleep?

Answer 46

cortisol levels get high

Question 47

what are the 2 types of cushings syndrome?

Answer 47

ACTH independent | ACT dependent

Question 48

what is the most common cause of ACTH independent Cushings syndrome?

Answer 48

steroid therapy | adrenal tumour may be the cause

Question 49

what are the ACTH levels like in ACTH dependent Cushings syndrome?

Answer 49

Levels are raised primarily

Question 50

what are the symptoms of cushings syndrome?

Answer 50

o Weight gain, muscle weakness and skin changes.