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Physiology of Endocrine System (DEFINITIONS (Exocrine Glands = Secrete…
Physiology of Endocrine System
DEFINITIONS
Exocrine Glands
= Secrete through a duct
Endocrine Hormone
= Blood borne, acts at distant sites
Endocrine Gland
= secrete into the blood
Paracrine Hormone
= Acts on adjacent cells
Endocrinology
= The study of hormones, their gland of origin, their receptors, the intracellular signalling pathways and their associated diseases
Autocrine Hormone
= Feedback on the same cell that secreted the hormone
Endocrine system functions:
Rapid adaptive changes
Chronic maintenance of metabolic environment
Communication
Integration of whole body physiology
Types of Hormone
Peptides
Released in burtsts
Hydrophilic - so water soluble
Stored in secretory granules
Cleared by enzymes
Example: Insulin
Synthesis: pre-pro hormone > pro hormone
Packaging: Pro hormone > Hormone
Storage: Hormone
Secretion: Hormone
Cannot diffuse through membrane, so they must attach to a receptor and activate a secondary messenger
Insulin binds to receptor. Phosphorylation occurs. Tyrosine kinase is activated (this is the second messenger). Cascade of effects occurs e.g. glucose uptake and anabolic reactions
Amines
Adrenaline is broken down by COMT (catechol-O-methyl transferase) into metanephrine
Noradrenaline is broken down by COMT into normetanephrine
Phenylalanine > L-Tyrosine > L-Dopa > Dopamine > Noradrenaline > Adrenaline
Adrenaline binding to
alpha adrenoreceptor
s leads to:
Vasoconstriction
Bowel muscle contraction
Sweating
Anxiety
Example: Adrenaline + Noradrenaline
Adrenaline binding to
beta adrenoreceptor
leads to:
Vasodilation
Increased heart heart
Increased force of contractility
Relaxation of bronchial smooth muscle
Fat Soluble
Long half life
Protein bound
Diffuse into cell
Slow clearance
Steroids, thyroid hormone
Iodothyronines
T3 = Triiodothyronine - more active, half life of 1 day
T4 = Thyroxine - less active, but more produced, half life of 5-7 days
Not water soluble - 99% are protein bound
Iodine + tyrosine on thyroglobulin > Iodothyrosines > T3 + T4, stored in colloid
Thyroid hormones - bind to receptors on nucleus of cell
TSH stimulates T3 and T4 to be cleaved from thyroglobulin
T4 is a reservoir for T3
Water Soluble
Short half life
Unbound
Bind to surface receptor
Fast clearance
Peptides, monoamines
Cholesterol Derivatives
Vitamin D
Binds to nucleus and stimulates mRNA production
Transported by vitamin D binding protein
Fat soluble
Adrenocortical + Gonadal Steroids
Some pass into nucleus to induce response e.g. oestrogen
Some bind to cytoplasm receptor, and then enter nucleus to induce transcription of mRNA e.g. cortisol
95% are protein bound
Steroid hormones are inactivated in the liver by reduction and oxidation or conjugation to glucoronide and sulphate groups
Bind to receptors in cytoplasm of cell
Control of Hormonal Secretions
Control of Hormone Action
Hormone receptor induction
- induction of LH receptors by FSH in follicle
Hormone receptor down regulation
- hormone is secreted in large quantities
Hormone metabolism
- increased metabolism reduces function
Synergism
- combined effects of two hormones amplified e.g. glucagon + adrenaline
Antagonism
- One hormone opposes another hormone e.g. glucagon antagonises insulin
Hormone Secretion Patterns
Pulsatile e.g. insulin
Circadian rhythm e.g. GH, TSH
Continuous e.g. prolactin
Release inhibiting factors e.g. somatostatin inhibits release of GH
Pituitary Gland
Anterior Pituitary
Dopamine > Ant. Pituitary > Decreased prolactin (prolactin stimulates breasts to produce milk)
GHRH = growth hormone releasing hormone > Ant. Pituitary > Growth Hormone > Liver > IGF-1 = insulin like growth factor 1 which increases cartilage formation, skeletal growth + protein synthesis
GH stimulates glucogenesis and inhibits insulin, increasing blood glucose levels
Somatostatin inhibits the release of GH
GH stimulates growth and protein synthesis
TRH = Thyrotropin releasing hormone > Ant. Pituitary > TSH = Thyroid stimulating hormone > Thyroid > T3 + T4
Thyroid hormone increases cardiac output and heart rate
No thyroid hormone = SLOW, too much thyroid hormone = FAST
Thyroid hormone controls rate of metabolic reactions and stimulates carbohydrate + fat metabolism
GRH = gonadotropin releasing hormone > Ant. Pituitary > LH + FSH > Gonads > Oestrogen + Testosterone
LH stimulates release of egg and progesterone release which thickens uterine wall
LH causes testosterone release from leydig cells
FSH stimulates oestrogen release - positive feedback stimulates LH release
Hypothalamus secretes hormones and blood which reach the anterior pituitary via hypothalamo-hypophyseal portal veins.
CRH = corticotropin releasing hormone > Ant. Pituitary > ACTH = adrenocorticotropic hormone > Adrenal glands > Glucocorticoids e.g. cortisol
ACTH stimulates release of sex hormones (androgens) from zona reticularis
ACTH stimulates release of adrenaline from adrenal medulla
ACTH stimulates adrenal cortex to release cortisol from zona fasiculata. Cortisol has anti-inflammatory effects
ACTH also stimulates release of aldosterone from zona glomerulosa but only a minor stimulation
Stimulated by CNS
Hypothalamus secreting a hormone to the ant. pituitary allows for negative feedback and amplification of a signal
Anatomy
Lies inferior to optic chiasm - so pituitary tumours can cause vision problems e.g. hemianopia
Connected to hypothalamus via infundibulum
Sits in pituitary fossa
Composed of anterior and posterior glands
Lies just below hypothalamus
Posterior Pituitary
ADH
Acts on smooth muscle cells to constrict blood vessels, increasing blood pressure. Also binds to aquaporins to reputake water
ADH is released in response to: Decreased blood volume, trauma, stress, increased osmotic pressure of blood
Stimulates ACTH release to increase aldosterone release and further increase fluid retention
ADH = anti pee, fluid retention, maintains blood volume
Synthesised in supraoptic nucleus of hypothalamus
Oxytocin
Oxytocin stimulates contraction of uterine smooth muscle until baby is born
Promotes onset of labour
When mammary glands are stimulated, oxytocin is released to release milk
Important for ejection of milk in breast feeding
Formed of neuronal tissue with glial cells
ADH and oxytocin have a very short half life so are regulated frequently
Hormone production is all done by the hypothalamus - STORED in posterior pituitary. Posterior pituitary does not produce any of its own hormones
Pituitary Dysfunction
Hormone excess -
prolactin - increased milk production, reduced fertility, amenorrhoea
ACTH - too much cortisol
GH - acromegaly, thick greasy sweaty skin
Hormone deficiency - cortisol deficiency can be fatal
Tumour mass effects - leads to fits, vision defects, headaches. This is due to the tumour pressing on surrounding structures
Pituitary dysfunction presents in three ways