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hypothalamus-pituitary axis Flashcards

1
Q

what are the different nuclei of the hypothalamus?

A 
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
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2
Q

what does the hypothalamus regulate?

A

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

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3
Q

where is the pituitary gland?

A

sits in the sella turcica of the sphenoid bone

surrounded by the cavernous sinus

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4
Q

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

A 
o	GH  all tissues
o	TSH  thyroid
o	LH and FSH  testis and ovary
o	Prolactin  breast
o	ACTH  adrenal
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5
Q

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

A

o Oxytocin  uterus

o ADH  kidneys

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6
Q

what artery has capillaries in the median eminence?

A

supraphyseal artery

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7
Q

what artery do hormones from the posterior pituitary travel through?

A

inferior hypophyseal artery

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8
Q

what nerves would a pituitary tumour affect?

A

nerves II, IV, VI, V1 or V2

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9
Q

what can pituitary tumours cause?

A

pituitary gigantism and pituitary apoplexy

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10
Q

where does the anterior pituitary grow from?

A

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

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11
Q

where does the posterior pituitary grow from?

A

forms from the diencephalon of the brain

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12
Q

what regulates development?

A

transcription factors

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13
Q

what transcription factor is important in pituitary development?

A

Pit1

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14
Q

what does a missing/mutated Pit1 cause?

A

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

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15
Q

what regulates the GH axis?

A

growth hormone releasing hormone from the hypothalamus

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16
Q

what regulates the TSH axis?

A

TSH hormone from the hypothalamus

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17
Q

what inhibits the TSH axis?

A

somatostatin

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18
Q

what does TSH stimulate?

A

the thyroid gland to make T3 and T4

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19
Q

what regulates the prolactin axis?

A

dopamine

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20
Q

what regulates the ACTH axis?

A

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

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21
Q

what does kisspeptin do?

A

kisspeptin stimulates GnRH –> LH and FSH

22
Q

describe what happens in primary underactivity

A

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

23
Q

describe what happens in secondary underactivity?

A

pituitary damage  problem stimulating target organ.

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

24
Q

explain primary overactivity

A

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

25
Q

give examples of causes of primary overactivity

A

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

26
Q

explain secondary overactivity

A

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

27
Q

what stimulates GH?

A

GHRH and ghrelin

28
Q

what inhibits GH?

A

somatostatin

29
Q

what does GH stimulate?

A

insulin-like growth factor production

30
Q

what does IGF stimulate and inhibit?

A

o Inhibits GF and GFHRH via negative feedback.

o Stimulates secretion of SS.

31
Q

what can a GHRH receptor mutation cause?

A

dwarfism

32
Q

what is acromegaly?

A

too much growth hormone

33
Q

how is acromegaly?

A

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

34
Q

what are the roles of GHRH?

A
  • 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.
35
Q

what type of receptor is the GHRH receptor?

A

GPCR

36
Q

explain how a GPCR reacts when a hormone binds

A
  • 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
37
Q

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

A

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

38
Q

what causes mccune albright syndrome?

A

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

39
Q

what does mccune-albright syndrome result in?

A 
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).
40
Q

which gender is mccune-albright syndrome more common in?

A

females

41
Q

how many receptors can somatostatin act on?

A

5

42
Q

what does ACTH do?

A

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

43
Q

what causes Cushing’s disease

A

too much cortisol

44
Q

what causes Addison’s disease

A

too little cortisol

45
Q

describe the circadian rhythm of cortisol

A
  • 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.
46
Q

what happens to cortisol levels when you have disrupted sleep?

A

cortisol levels get high

47
Q

what are the 2 types of cushings syndrome?

A

ACTH independent

ACT dependent

48
Q

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

A

steroid therapy

adrenal tumour may be the cause

49
Q

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

A

Levels are raised primarily

50
Q

what are the symptoms of cushings syndrome?

A

o Weight gain, muscle weakness and skin changes.

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