MEH - Hypothalamic Pituitary Axis Flashcards
Why isn’t the post pituitary a true gland?
As it releases hormones that have been synthesised by the hypothalamus not synthesised itself
What hormones does the hypothalamus make (6+2)?
Oxytocin
ADH
TRH GHRH GHIH - somatostatin PIH - Dopamine GnRH - stimulates FSH/LH CRH
What is a tropic vs trophic hormone?
Tropic hormones have other endocrine glands as their target organ. Hypothalamus and anterior pituitary secrete tropic hormones.
Trophic hormones are growth hormones - ones that affect hyperplasia/hypertrophy
Where are oxytocin and ADH made and how do they travel to the posterior pituitary?
Both made in supraoptic and paraventricular nuclei of hypothalamus and travel to posterior pituitary by nerve cell axons. Post pituitary then releases them into the blood to act directly on target tissues
Are the anterior and pituitary similar or separate entities? Where are they derived from embryologically? Which is directly connected to the hypothalamus?
Embryologically distinct
Ant pituitary - from primate gut tissue
Post pituitary - from primitive brain tissue
Post pituitary is physically connected to the hypothalamus
What 6 hormones does the Ant pituitary secrete?
TSH Growth Hormone FSH LH ACTH Prolactin (inhibited by PIH stimulated by TRH)
Explain how the anterior pituitary is autocrine, paracrine endocrine and neurocrine
Auto and paracrine - ant pituitary hormones affect self and neighbouring cells
Neurocrine - from hypothalamus
Endocrine - via blood to target tissues
What is the stalk of the pituitary called? What pathology can occur here?
Infundibulum
Tumours
What is the hypothalamus known as the link between?
Neural and endocrine
How do hormones travel from the hypothalamus to the anterior pituitary?
Via nerves in the hypothalamus to the median eminence (blood vessels at base of brain) then via hypopophyseal portal system (blood vessels) to the anterior pituitary
What is the median eminence used for?
Storage of hormones before travelling to ant pituitary
What is the role of negative feedback in the body?
To maintain homeostasis - to keep levels of chemicals in the body within physiological ranges
What are 8 functions of hormones that have come from the hypothalamus and pituitary gland?
Body growth Sex hormones - Reproduction Stress response Milk production Lactation Puberty Adrenal gland function Thyroid gland function Water homeostasis (ADH)
What does GHRH stimulate and where (2)?
Goes to liver (and skeletal muscle) which is stimulated to produce IGFs. IGFs stimulate growth (main action is via IGFs)
GHRH also stimulated growth directly in many tissues
Where do LH and FSH target?
Ovaries and testes - sex hormone production
How does the short and long negative feedback work?
Long loops are anything from hormone 3 (e.g. cortisol) so cortisol negatively feeds back to ACTH and CRH
Short loops are from hormone 2 to hormone 1
What is the most important hormone for post natal growth?
Growth hormone
Where is growth hormone produced? Stimulated by what? Inhibited by?
Anterior pituitary
Stimulated by hypothalamus GHRH
Inhibited by somatostatin (GHIH)
What kind of hormone is growth hormone?
Protein hormone - signal peptide cleaved before proper folding
Why can’t diabetics take oral insulin?
Because insulin is a growth hormone and so stomach proteases would degrade insulin and it wouldn’t work
Which two tissues can produce IGFs in response to GH?
Liver and skeletal muscle
What is the role of GH and IGFs in childhood and teenage years?
GH - stimulates long bone growth (length and width prior to epiphyseal closure. width after epiphyseal closure)
IGFs - stimulate both bone and cartilage growth
What is the role of GH and IGFs in adults (4)?
Maintains muscle and bone mass
Promote healing and tissue repair
Modulating metabolism and body composition
What controls GH secretion?
Hypothalamus –> GHRH GHIH (Somatostatin)
Apart from GH and IGFs what 4 other hormones can influence (stimulate or inhibit) growth?
Insulin - via IGF receptors
Oestrogen - decrease somatic growth and promote closure of epiphyseal growth plates
Androgens - acceleterate pubertal growth
Thyroid hormones - CNS development and GH secretion
What kind of rhythm is growth hormone release under? What 5 other things can INCREASE GH release apart from GHRH from hypothalamus?
Diurnal rhythm Sleep - surge of GH Decreased glucose or fatty acids Exercise Stress (trauma/surgery/fever) Fasting
What three things can have a negative effect on GH release?
REM sleep
Obesity
Increase in glucose/fatty acids
What is the feedback mechanism for GH?
2 negative long loops - IGFs acting negatively on GH and GHRH
1 positive long loop - IGFs acting to stimulate somatostatin from hypothalamus
1 short loop - GH acting to stimulate somatostatin
What can happen in childhood growth hormone deficiency? What kind of signs would you see? How do you treat?
Pituitary dwarfism Proportionate type of dwarfism Complete or partial Both respond to recombinant GH therapy Delayed or not sexual development during teen years and height below 3rd percentile on standard growth charts
What does growth hormone excess lead to in children? Adults?
Children - gigantism
Adults - acromegaly
Gigantism is rare but what is it often caused by?
Pituitary adenoma
What does acromegaly mean?
Large extremities - Hands, feet, lower jaw
How does GH exert it’s effect on cells?
Directly - via JAK kinases - intracellular kinases associated with TK receptor. Activates signalling pathway - one of which activates transcription factor activation and IGF production.
Indirectly - via IGFs - Insulin receptor, hybrid receptor (insulin and IGF1), IGF1R and IGF2 receptor (foetal)
What effects do insulin and IGF1 have on metabolic effects/mitogenic effects? Via what receptors (3)?
Insulin via insulin receptor main effect is metabolic but also some effect on mitogenic
Insulin and IGFR both act on a hybrid receptor - mainly mitogenic effect but some metabolic effects
IGF1 acts on IGF1R mainly mitogenic but some metabolic effects
What kind of receptors are insulin receptors/hybrid/IGF1?
Are GH receptors the same?
Tyrosine kinase
GH same - tyrosine kinase
What happens to IGF2 in adults? Does it activate tyrosine kinase too?
No tyrosine kinase activity
It’s receptor targets it for lysosomal degradation
Name 3 hormones that inhibit growth
Somatostatin (GHIH)
Glucocorticoids (cortisol)
Oestrogen
What are the main actions of IGFRs via tyrosine kinases?
Hypertrophy
Hyperplasia
Increased rate of protein synthesis
Increased lipolysis in adipose
