Hypothalamus, pituitary and growth hormone Flashcards
What processes does the hypothalamic pituitary axis modulate?
- growth
- milk secretion
- lactation
- adrenal gland function
- thryoid gland function
- puberty
- water homeostasis
- reproduction
Where does the anterior pituitary gland develop from in embryoloigcal development?
primitive gut tissue
Where does the posterior pituitary gland develop from in embryoloigcal development?
neuroectoderm
Where does the pituitary gland sit?
in a pocket of bone in the skull called the sella turcica
What hormones are released from the posterior pituitary gland on neuronal stimulation from the hypothalamus
- oxytocin
- ADH
Where are ADH and oxytocin initially produced from?
the supraoptic and paraventricular nuclei of the hypothalamus.
They then travel down nerve axons to the posterior pituitary where they’re released into blood
What effects do ADH and oxytocin have?
ADH: stimulates increased water absorbtion by kidneys
Oxytocin: stimulates release of milk on suckling reflex and contracts uterus during birth
Describe the path of hormones released by the anterior pituitary
- hormones from hypothalamus travel down axons to the median eminence (primary capillary plexus) in the pituitary stalk where they’re released into the portal system
- They travel through portal system to the anterior pituitary where they activate or inhibit release of other hormones from target cells
- these other hormones are passes into the general circulation
Which 6 hormones are produced by the hypothalamus and travel to the anterior pituitary?
- Remember PTC tripple G
- Prolactin release- inhibiting hormone (PIH)
- Thyrotropin releasing hormone (TRH)
- Corticotrophin releasing hormone (CRH)
- growth hormone releasing hormone (GHRH)
- growth hormone inhibiting hormone (GHIH or somatostatin)
- gonadrotrophin releasing hormone (GnRH)
What stimulates release of prolactin release inhibiting hormone?
dopamine
What 6 hormones are released from the anterior pituitary gland and what stimulates (or inhibits) their release?
- PTA GLF
- Prolactin (inhibited by PIH, stimulated by TRH)
- TSH (stimulated by TRH)
- Adenocorticotropic hormone (by CRH)
- Growth hormone (stimulated by GHRH, inhibited by GHIH)
- LH (stimulated by GnRH)
- FSH ( stimulated by GnRH)
What does TSH do?
- stimulates secretion of thyroid hormone from thyroid gland
- increases metabolic rate
What does Adrenocorticotrophic hormone (ACTH) do?
- stimulates secretion of hormones (mainly cortisol) from the adrenal glands as part of the long term stress response
- cortisol stimulates gluconeogenesis and other metabolic actions
- also increase BP by increasing fluid retention
What does prolactin do in the body?
- stimulates mammary glands to develop and also milk secretion
What does LH do?
- travels to gonads
- stimulates ovulation and sex hormone release
What does FSH do?
- travels to gonads and stimulates gamete production
Describe the negative feedback in the hypothalamic- pituitary- adrenal axis?
- CRH causes ACTH release which causes cortisol release
- cortisol inhibits release of CRH and ACTH when its levels become suffienctly high
What does growth hormone release cause in liver and muscle? What effects does this have in adults?
- insulin- like growth factor release
- GH and IGF help maintain muscle and bone mass and promote healing and repair as well as modulate metabolism and body composition
Why are growth hormone and insulin like growth factor important in children and teens?
- GH promote long bone growth
- length ways before epiphyseal growth plates fuse
- width ways after they fuse
- IGF stimulate both bone and cartilage growth
Why is growth hormone not orally active?
because it is a 191 amino acid long poly peptide which would be broken down by proteases in the stomach
What things increase growth hormone release?
- onset of deep sleep
- stress (trauma, surgery, fever)
- exercise
- decrease in glucose of fatty acids
- fasting
What things decrease growth hormone release?
- REM sleep
- high glucose or fatty acids
- obesity
What substance are produced in the brain during stress and sleep which stimulate GH release?
- serotonin, a- adrenergy- stess
- dopamine- sleep
- lead to increased GHRH by hypothalamus and decreased GHIH (somatostain) release by hypothalamus
- lead to increased GH release from pituitary
What substances are produced in the body which inhibit GH release which ARE NOT a part of negative feedback
- B- adrenergy
- Glucose
- FFA
Describe the short and long loop negative feedbacks of GH release
- short loop: high levels GRHR will inhibit the hypothalamus from secreting more GHRH
Long loops: - GH will inhibit GHRH release
- insulin like growth hormone (AKA somatomedin) will inhibit GH and GRHR release
What is the result of growth hormone deficiency in children?
- pituitary dwarfism
- a proportionate dwarfism, can be caused by partial or complete loss of GH
- leads to slow growth and delayed sexual development
How can pituitary dwarfism be treated?
GH therapy
What does excess GH from birth and excess GH of adult onset cause?
- if from birth= giantism
- if aquired as adult= acromegaly
What type of receptors do growth hormones bind to, what effects do they have?
- janus kinases
- increase transcription of IGF
What type of IGF is present mainly in adults and foetuses?
in adults: IGF1
in foetuses: IGF2
WHat receptors do IGF exert their effect on?
IGF receptors (distinct from GH receptors) and hybrid receptors
What effect does activation of a hybrid of IGF1 receptor have?
- partial metabolic effects (mainly by insulin only receptors)
- mainly mitogenic effects: hypertrophy, hyperplasia, increase protein synthesis increase lipolysis in adipose tissue
What is the cause of most pituitary disorders?
tumours - mostly benign
What effect will a benign pituitary tumour have?
- decreased secretion , vision loss, headaches
- very few will caused hypersecretion
What can be tested for in blood to check thryoid, gonadal and prolactin axis??
thyroid: fT4, TSH
gonadal: LH, FSH, testosterone, oestradiol
Prolactin: serum prolactin
How is the HPA (adrenal) axis tested for to test its funcitoning correctly?
need to test cortisol but this changes lots through day so do dynamic test:
- give insulin to pt and check that ACTH goes up as it should
- Give steroids (dexamethasone) and check that ACTH goes down
How can GH axis be tested for to ensure its functioning correctly?
- give insulin and check GH/ GHRH increases
- give glucose and check that GH decreases
What else can be done to check for signs of pituitary tumour?
- MRI
- vision test- they may have bi- temporal impingement of optic nerves causing loss of vision on outside half of eye (tunnel vision)
which hormones will increase and which hormones will decrease in a non functional pituitary tumour?
- blocks hormones moving from hypothalamus to pituitary
- ADH, GH, LSH, FSH, TSH, ACTH all decrease
- prolactin increase (under negative control)
Which hormones are unlikley and more likely to become deficient in a non functioning pituitary tumour?
- TSH, LH and FSH unlikely to become deficient (but does happen)
- GH, ACTH, ADH likely to decrease
- prolactin likely to increase but not more than 5,000
What will be the effect to the pt of a non functioning pituitary tumour?
- GH deficient first- leads to lower QoL, depression, shortness in children
- headaches, tunnel/ double vision, nausia experienced due to impingement on brain
- gonadotrophin sometimes deficient= loss of periods, loss of pubic hair, low libido, man boobs
- TSH deficient leads to hypothyroidism
- ACTH deficient leads to tiresness, dizziness, low BP, low sodium
- ADH low leading to increased urination and need to drink (often as a result of the inflammation from surgical removal)
- prolactin high but less than 5,000 leads to erectile dysfunction, hardened breast tissue, light, irregular periods, hypogonadism
How is a non funcitonal pituitary tumour treated?
surgical removal
What is most common cause of prolactin increase over 5,000 and what are symptoms?
prolactinoma:
- amenorrhea
- hypogonadism (underactive overies and testis)
- galactorhea (milk discharge from nipples)
- hardened breast tissue
- erectile dysfunction
other than prolactinoma what else can cause hyperprolactinaemia?
- pregnancy
- severe stress
- exersize
- drugs like antiphycotics and antidepressants
- sarcoidosis
How is hyperprolactinaemia (including due to prolactinoma) treated?
- dopamine receptor agonists- leads to more dopamine so more inhibition of prolactin
- eg. cabergoline
What is the common cause and consequence of GH excess?
GH secreting tumours
- usually lead to acromegaly
What are symptoms of acromegaly?
- vision loss and headaches common (these tumours usually big)
- nose broadens, jaw widens,facial features become more coarse, lips becomes thicker, hands and feet enlarge
- excessive sweating
- premature CVS death
- increased colonic tumour risk
- hypertension and diabetes
- thyroid cancer
- sleep aponea
- back pain, kyphosis
- skin tags
- often comes with hyperprolactinaemia and hypopituitarism
What is diabetes insipidus?
- excessive urination and need to drink due to ADH deficient
- eg in hypopituitarism, head injuries ect
What is the result of ACTH excess?
cushings syndrome
How can acromegaly be treated?
- surgical removal or adenoma
- radiation therapy
- high levels of dopamine agonists
- synthetic somatostain (GHIH)
- GH receptor antagonists like pegvisomant
