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what is a hormone
a chemical mediator secreted by an endocrine gland into the blood where it is then transported to its target cells
how can a three hormone sequence start
something has to trigger the sequence
how can the three hormone sequence be described as
a domino effect
what is the structure of the pituitary gland
posterior pituitary gland
anterior pituitary gland
structure of posterior pituitary gland
neurohypophysis
predominantly made of nervous tissue
connects by neural pathway
structure of anterior pituitary gland
adenohypophysis
predominantly glandular epithelial tissue
connects by unique vascular link
what are the differences between the 2 pituitary glands
arise from different tissues embryonically
serve different functions
subject to different control mechanisms
release of peptide hormones from the anterior or posterior pituitary
directly controlled by the hypothalamus
what is unique to posterior pituitary gland
does NOT make hormones
hormones are stored and released here
what is the posterior pituitary gland an extension of
extension of the hypothalamus
hypothalamus structure
cell bodies of neurons in hypothalamus in supraoptic and paraventricular nuclei
axons pass through stalk and terminals on capillaries in posterior pituitary
what are the peptide hormones the neuronal cell bodies produce in the hypothalamus
oxytocin
vasopressin
oxytocin main role
contraction of the uterine muscle to help expel infant during childbirth
secretion increased by reflexes originating within birth canal during birth
what does oxytocin promote
promotes ejection of milk from mammary glands during breast feeding
secretion increased by suckling
influences social behaviours
mating/bonding with infant
what is the synthetic oxytocin injection
syntocinon
used to induce labour and prevent postpartum haemorrhage
what is vasopressin also known as
anti-diuretic hormone (ADH)
what does vasopressin enhance
enhances retention of water by nephrons during urine formation
primary regulator of water balance
what does vasopressin V2 receptors binding increase
increases water permeability in distal tubule and collecting ducts leading to increased water reabsorption
what does vasopressin have a role in
minor role in regulating blood pressure
contraction of arteriolar smooth muscle (vessel pressor effect)
what does vasopressin V1 receptor binding increase
vasoconstriction
what could lack of vasopressin production or release lead to
diabetes insipidus
is diabetes insipidus different to
slightly different to type I and type II diabetes
symptoms of lack of vasopressin production or release
polyuria (excessive dilute urine)
polydipsia (extreme thirst)
untreated can lead to shock-like symptoms (hypotension, tachycardia, tachypnea etc.)
what can untreated shock-like symptoms lead to
hypernatremia
what can hypernatremia be treated with
vasopressin
or desmopressing (doesn’t cause vasoconstriction)
anterioir pituitary
synthesises hormones and releases them into bloodstream
what are the 5 cell types in the anterior pituitary gland
somatotropes
thyrotropes
corticotropes
gonadotropes
lactotropes
what hormone do somatotropes secrete
GH (growth hormone)
also known as somatotropin
what hormone do thyrotropes secrete
TSH (thyroid stimulating hormone)
what hormone do corticotropes secrete
ACTH (adrenocorticotrophic hormone)
what hormones do gonadotropes secrete
FSH (follicle stimulating hormone)
LH (luteinising hormone)
what hormone lactotropes secrete
PRL (prolactin)
FSH and LH
travel to gonads and stimulate secretion of estradiol, progesterone, and testosterone
GH
stimulates secretion of IGF-1 from liver and other cells and protein synthesis and carbohydrate and lipid metabolism in many tissues
TSH
stimulates thyroid hormone form thyroid gland
ACTH
stimulates cortisol secretion by adrenal cortex and stimulates adrenal cortex growth
prolactin
enhances milk production and breast development in females
what are the major factors controlling secretion
hypothalamic hormones (releasing and inhibitory hormones)
neural or hormonal inputs to stimulate or inhibit secretion
somatostatin (GHIH) inhibits GH and TSH
dopamine (PIH) inhibits PRL
What are feedback loops
stops hypothalamus from making more hormones once its reached its target
control of anterior pituitary hormones
not secreted at a constant rate
secretion independent of each other
feedback by target-gland hormones
hypothalamic pituitary (hypophyseal) portal system
unique vascular between hypothalamus and anterior pituitary- direct capillary to capillary bed
upon arrival, hypothalamic hormones bind to specific receptors on specific cells in anterior pituitary
what is a GHRH
growth hormone releasing hormone
where do GHRH from the hypothalamus bind to
bind to receptors on somatotroph cells in anterior pituitary, triggering the release of GH
what do GH stimulate the growth and development of
net synthesis of proteins
lengthening of long bones
increase in size and number of cells in soft tissues
does GH directly affect tissues
no
doesn’t directly affect tissues but works by stimulating IGF
what is IGF
insulin-like growth factor
what other factors influence growth
genetics
adequate diet
chronic disease
stressful environment
other growth influencing hormones e.g. thyroid hormone, insulin estrogens’s, and androgens
what is the primary GH deficiency
pituitary defect
what is the secondary GH deficiency
hypothalamic dysfunction
lack of GHRH or IGF or lack of tissue response
why does a GH deficiency lead to short stature
due to reduced skeletal growth and reduced muscle protein synthesis and increased fat deposition
what sort of effects does GH deficiency have in adults
muscle effects
e.g. at risk of heart failure
how can GH deficiencies be treated
somatotropin treatment
recombinant GH
what is an excess of GH often due to
benign tumour of somatotrophs
what does an excess of GH in childhood often result in
gigantism
what does an excess of GH in adulthood often result in
acromegaly
thicker bones and soft tissue proliferation
bone thickening in face and extremities
peripheral nerve disorders as nerves trapped
what is the treatment of excess GH
surgery
somatostatin analogues
IGF inhibitors
what are examples of different drugs controlling GH secretion
somatorelin
somatostatin
somatotrophin
mecasermin
somatotrelin
44 amino acid residue peptide
diagnostic for GH secretion (induces secretion within minutes)
somatostatin
14 amino acid residue peptide produced by hypothalamus
inhibits release of GH, TSH, insulin, and glucagon and most GI hormones
somatotrophin
given for short stature e.g. pituitary dwarfism, turners syndrome etc.
prepared by recombinant DNA technology
also used illicitly by athletes to increase muscle mass
mecasermin
human recombinant IGF-1
treatment of growth failure in children lacking adequate IGF-1
why are some drugs for controlling GH secretion easy to make in a lab
just need to know how to put the number of amino acids needed together
what is ACTH synthesised as part of
synthesised as part pf precursor molecule- proopiomelanocortin (POMC)
what are the 3 molecules POMC is cleaved into
ACTH
endorphin
MSH
what do corticoropes mainly produce from POMC
ACTH
what do keratinocytes produces
alpha-MSH
what do appetite suppressing neurons produce
alpha-MSH to control food intake
what do neurons in the CNS produce
endorphins to suppress pain
what is ACTH released by and what does it stimulate
released by CRH from hypothalamus
stimulates cortisol secretion in the adrenal cortex
where are adrenal glands found
just above the kidneys like little caps
what are the 3 zones of the adrenal cortex
zona glomerulosa- outermost
zona fasciculata- middle
zona reticularis
what is zona glomerulosa responsible for
aldosterone release
what is zona fasiculata responsible for
cortisol and androgens
what is zona reticular responsible for
epinephrine and norepinephrine release
how many steroids are produced from cholesterol
>30 steroids
corticosteroids
what is cholesterol converted into
converted into pregnenelone and then series of enzymatic reactions to different steroid molecules
what are the 3 categories of steroid produced in distinct zones
mineralocorticoids
glucocorticoids
sex hormones
mineralocorticoids
aldosterone
influences electrolyte balance
glucacorticoids
cortisol
major role in glucose
protein and lipid metabolism and response to stress
sex hormones
dihydroepiandrosterone (DHEA)
involved in mail sexual development
aldosterone
major mineralocorticoid
essential for life
acts on distal and collecting tubules
what are the functions of the mineralocorticoids
promotes NA reabsorption in kidney
increases K+ and H+ excretion in urine
Na retention induces water retention, expanding ECF volume
thus increases blood pressure in the long-term due to increased blood volume
what is aldosterone secretion increased by
activation of renin angiotensin aldosterone system (blood volume)
direct stimulation of adrenal cortex by ride in plasma [K]
what is control of aldosterone secretion largely independent of
ACTH and anterior pituitary
cortisol
major glucocorticoid
what role do glucocorticoids have in metabolism
increase blood glucose concentration. at expense of protein ad fat stores
stimulate hepatic gluconeogenesis
inhibits glucose uptake by several tisssues
stimulates protein breakdown in several tissues, especially muscle
stimulates lipolysis in adipose tissue to provide alternative source of free fatty acids to tissue rather than using up glucose
what other roles do glucocorticoids have
permissive actions for other hormones
role in adaptation to stress
anti-inflammatory/immunosuppresie effects
permissive actions for other hormones
e.g. need sufficient cortisol for catecholamines to induce vasoconstriction
lack of cortisol could lead to circulatory shock in stressful situation where you need acute vasoconstriction
role in adaptation to stress
stress increases cortisol secretion
cortisol in fight/flight situation favours providing glucose and amino acids/free fatty acids as immediate source of energy
anti-inflammatory/immunosuppresive effects
inhibits pro-inflammatory cytokines, phagocytosis, neutrophil recruitment, fibroblast inflammation
what is used for the treatment of several inflammatory diseases
corticosteroids
what is diurnal rhythm
your sleep and wake cycles that show cortisol levels during this time
facts about the diurnal rhythm
highest in morning
lowest at night
related to sleep wake cycle
important for interpreting blood samples
influences time of surgery
what types of stress is cortisol involved in
physical stress
physiological/emotional factors
cortisol in physical stress
hypoglycaemia
trauma (injury, surgery, excess heat or cold, pain, infection)
intensive exercise
cortisol in physiological/emotional factors
anxiety
fear
sorrow
what does cortisol in stress do
stimulates protein catabolism and gluconeogenesis
inhibits glucose uptake by tissues
stimulates lipolysis to free fatty acids
inhibits inflammation and specific immune response
inhibits non-essential functions
corticosteroids in therapy
immunosuppressive/anti-inflammatory effects
mineralocorticoid activity and K+ loss
effect on Ca2+-metabolism and bone metabolism
effects on muscle
atrophy of adrenal cortex (treatment must not be stopped suddenly)
what are the types of corticosteroid dysfunction
aldosterone hyper secretion
cortisol hyper secretion (Cushing’s syndrome)
what is the primary or conn’s syndrome aldosterone hyper secretion
hyper secreting adrenal tumour made of aldosterone-secreting cells