hormones Flashcards
Explain endocrine system and hormone action
Endocrine system Organs that secrete a hormone into the blood are called endocrine glands. Release ‘chemical messengers’
hormone action:
molecular level: Regulation of: Gene transcription, Protein Synthesis & degradation, Enzyme activity, Protein conformation
Protein:protein interactions
cellular level: Regulation of: Cell division, Differentiation, Death (apoptosis), Motility, Secretion, Nutrient Uptake
whole body: Regulation and integration of:Ionic and fluid balance, Energy Balance(metabolism), Coping with the environment, Growth and development, Reproduction
Chemical nature and mechanism of action of hormones
chemical nature of hormones:
Steroid hormones
Cholesterol derivatives
e.g., Testosterone, Oestrogen,
Cortisol
Peptide hormones
e.g., Growth hormone, Oxytocin,
Parathyroid hormone
Amino acid derived hormones
e.g., Thyroid hormones
& catelcholamines
mechanism of action of hormones:
steroid hormones:
composition=cholesterol
location of receptor=cytosol or nucleus
mechanism of action=bind DNA/modify transcription
speed=slower
longevity=more permanent
examples=testosterone, oestrogen
peptide hormones:
composition=amino acids
location of receptor=cell surface
mechanism of action=2nd messengers
speed=rapid
longevity=temporary
examples=ADH, growth hormone
Endocrine-negative feedback
*The hypothalamus receives sensory inputs
*Detect challenges in both the internal and external environments
*Negative feedback
*Some positive feedback loops (eg. oxytocin and parturition)
The nervous system and endocrine system are tightly integrated
Negative feedback= is seen when the output of a pathway inhibits inputs to the pathway
(PITUITARY GLAND) Location & structure
Pituitary gland - A small structure at the base of the brain which releases hormones that, in turn, controls the activity of the body’s other hormone glands
((Optic chiasm (optic nerves crossing)
Pituitary lies inferior (below) to the hypothalamus with the optic chiasm between))
Anterior lobe (pars distalis)((always below optic chiasm))
Portal blood vessels connect pituitary and hypothalamic capillary beds
Posterior lobe (pars nervosa)
Nerve fibres originate in the hypothalamus and transport hormones to posterior pituitary
(PITUITARY GLAND) posterior lobe
*Cell bodies: Paraventricular nucleus & Supraoptic nucleus
*Both nuclei produce both hormones.
*Both produced from the same pro-hormone
Release 2 hormones:
Oxytocin :
Controls milk release from lactating breast
Controls uterine contraction at onset of labour
Interaction of oxytocin with its receptors raises the level of intracellular calcium in the myoepithelial cells of the mammary gland.
Vasopressin(Anti-diuretic hormone, ADH):
Acts on kidneys to re absorb water-regulates blood osmolarity and urine output
Increased plasma osmolarity eg hemorrhage/dehydration stimulates osmoreceptors in hypothalamus
(PITUITARY GLAND) anterior lobe
‘Regulator’ of the endocrine system
Secretes 6 different hormones
Most of which regulate the secretions of other endocrine organs (tropic hormones):
*Growth Hormone ->bone, skeletal muscle, liver
*Prolactin -> mammary glands
*Adenocorticotropic hormone (ACTH) ->adrenal glands
*Thyroid stimulating hormone (TSH) ->thyroid gland
*Follicle stimulating hormone (FSH) ->ovaries/testes
Luteinising hormone (LH) ->ovaries/testes
(PITUITARY GLAND)anterior pituitary- Relationship with the hypothalamus
Hormones from the hypothalamus control release of anterior pituitary hormones/secretory activity of the anterior pituitary
GnRH-stimulates FSH+LH
GHRH-stimulates growth hormone
SS-inhibits growth hormone
TRH-stimulates TSH
DA(dopamine)-stimulates prolactin
CRH-stimulates ACTH
(PITUITARY GLAND) The role of growth hormone (GH)
Synthesised and stored in somatotrophs
Principle targets bone and skeletal muscle
Stimulates growth in children and adolescents but continues to exert important effects throughout adult life
direct metabolic affect of GH:
Anabolic
Glucose sparing with an anti-insulin action; protects against hypoglycaemia
liver:
- Increases gluconeogenesis
- Increases protein synthesis
- Stimulates IGF production
Muscle:
- Decreases glucose uptake
- Stimulates aa uptake/protein synthesis
- Inhibits protein breakdown
= Increased muscle mass
Adipose tissue:
- Decreases glucose uptake
- Increases lipolysis
= Decrease in fat deposits
(PITUITARY GLAND)Disease states associated with GH
GH excess (gigantism)
*Gigantism refers to abnormally high linear growth due to excessive action of IGF while the epiphyseal growth plates are open during (children)
*Normal body proportions as soft tissues are also affected
GH excess: Acromegaly
- Increased growth hormone later in life after fusion of epiphyses (growth plates)
ACROMEGALY:
-course facial features
-enlarged hands and feet
-protruding jaw and separation of teeth
-enlarged tongue and thickened lips
-deep voice
-Cardiomegaly
-diabetes
GH insufficiency in children:
- ‘Pituitary dwarfism’
- Slow growth rate below 3rd centile on age/height or bone chart
- Normal body proportions
- Poor muscle development, excess subcutaneous fat
(THYROID GLAND)Position and structure
Fully developed by week 12 of gestation
Responsive to TSH at 22 weeks
Capable of producing T3/T4 at 14 weeks
Thyroid hormones crucial for subsequent fetal growth and development
Discrete organ, adheres to the trachea.
2 large (asymmetrical) flat lobes connected by isthmus
Regulated by the hypothalamus and pituitary
*Functional unit = Follicle (200-300μm in diameter)
*1000’s in each gland!
Each follicle consists of a layer of follicular cells (simple cuboidal epithelial) surrounding a colloid-filled cavity
(THYROID GLAND)Structure and synthesis of triiodothyronine (T3) and thyroxine (T4)
Triiodothyronine (T3) and thyroxine (T4)
The thyroid secretes about 80-100 ug of T4, but only 5ug of T3 per day.
However, T3 has a much greater biological activity (about 10 X) than T4.
T4 and T3 contain four and three atoms of iodine per molecule, respectively
Hormone class
Amino acid derived
Tyrosine
Iodinated
<0.5% of T3 & T4 present in ‘free form’
In plasma, bound to:
1) Thyroxine-binding globulin
2) Albumin
(THYROID GLAND)Thyroid hormone synthesis
Triiodothyronine (T3) and thyroxine (T4)
Synthesis requires 2 principle raw materials:
- Tyrosines
Provided by thyroglobulin
Secreted by follicular cells into lumen of follicle as colloid - Iodine
Iodine is essential requirement (min 75ug per day)
Iodide is pumped into follicular cells against concentration gradient (40x blood concentration)
Dietary iodide is oxidized to iodine
advantages of this system:
The thyroid gland is capable of storing many weeks worth of thyroid hormone (coupled to thyroglobulin)
If no iodine is available for this period, thyroid hormone secretion will be maintained
(THYROID GLAND) Major physiological effects of T3 & T4
90% of thyroid hormone released is T4
T3 has a much greater biological activity
Enzymatic conversion of T4 into T3 in peripheral tissues (liver, kidneys & skeletal muscle)
Thyroid hormone binds to intracellular receptors
Complex with thyroid response elements (TRE) that bind DNA & influence gene expression
T3–THR complex binds to thyroid response elements (TREs) within DNA
→ stimulates transcription/translation of a number of proteins
↑ Cellular metabolism
↑ Cellular oxygen consumption
↑ Cellular glucose
↑ Circulation and respiration
Promote nervous system and skeletal development
Clinically, these hormones help maintain normal:
* Energy levels
* Weight
* Thermoregulation
* Heart rate
* GI motility
Mood
Cardiovascular
➢Increased cardiac output
➢Increased heart rate and contractility
Increases basal metabolic rate
➢Important in temperature regulation &
adaptation to cold environments
➢O2 consumption and heat production
➢Increases mobilization & utilisation of
glucose, fat, protein
Bone growth
➢Synergy with growth hormone
➢CNS development & function
➢Thyroid hormone deficiencies can result in mental impairment and short stature
Respiratory effects
Skeletal muscle function
Regulation of reproductive function
Synergy with catecholamines
(THYROID GLAND) regulation of thyroid hormone secretion
Hypothalmic-pituitary axis: Negative feedback
TSH stimulates every aspect of thyroid function including:
Promoting the release of thyroid hormones into blood stream
Increasing the activity of the iodide pump and iodination of tyrosine to increase production of thyroid hormones
(THYROID GLAND) Disease states-hypothyroidism
Hypothyroid
* Underactive thyroid
In general metabolic rate decreases and weight gain
Symptoms:
* Dry, cold skin
* Sensitivity to cold
* Weight gain despite loss of appetite
* Impaired memory
* Mental dullness
Lethargy
Clinical exam:
* Reduced metabolic rate
* Reduced cardiac output
Diagnosis:
* Low plasma levels of ‘free’ T3 and T4
Treatment
Thyroxine. Dose determined by TSH monitoring
Causes:
* Iodine deficiency ->endemic goitre
* Autoimmune disease ->Hashimoto’s thyroiditis
Iodine deficiency (endemic goitre)
●Insufficient dietary iodine
●Insufficient amounts of T3 & T4
●Abnormally high TSH
●Abnormal growth of the thyroid due to the trophic effects of TSH
Hashimotos disease
*Antibodies against thyroglobulin or thyroid peroxidase
*Interferes with thyroid hormone synthesis
*Antibodies also against TSH receptor
Prevents stimulation of T3 & T4 release
Most common cause of hypothyroidism
Congenital hypothyroidism:
Thyroid hormones are essential for normal brain development & growth
*Cretinism – 1 in 4000 births
*Intellectual disability
*Short disproportionate body
*Thick tongue and neck
* Lack of gland or incorrect hormone biosynthesis
Intellectual disability if treatment later than 3 months
(THYROID GLAND) Disease states-hyperthyroidism
Hyperthyroid
* Overactive thyroid
In general metabolic rate increases and weight loss
Symptoms:
* Loss of weight
* Excessive sweating/intolerance to heat
* Palpitations and an irregular heartbeat
* Anxiety and nervousness
* Exopthalamus
Clinical exam:
* Raised metabolic rate & oxygen consumption
* Increased heart rate
Hypertension
Treatment:
* Surgical removal of all or part of the thyroid
* Ingestion of radioactive iodine that selectively destroys the most active thyroid cells
Drugs that Interfere with the gland’s ability to make T3/T4
Cause: Graves’ disease
* Abnormal antibodies that mimic TSH
* Activates TSH receptor inducing T3/T4 release
* Characterised by goitre, exopthalmos and lid retraction
Muscle weakness, heart palpitations, irritability
(ADRENAL GLANDS)Position and structure of both the outer cortex and inner medulla
A pair – lie above the kidneys
Each gland enclosed in a fibrous capsule surrounded by fat
Each gland equivalent to 2 endocrine glands
Inner: Adrenal Medulla
Outer: Adrenal cortex (->Under hormone control)
Function independently but share a common blood supply and play a role in response to stress
6-10g
Rich blood supply – adrenal arteries arise directly from the aorta
Blood flows through the cortex and drains into the medulla
layers of adrenal glands:(out -> in)
within cortex:
capsule
zona glomerulosa
-mineralcorticoids(aldosterone)->salt
zona fasciculata
-glucocorticoids(cortisol)->sugar
zona reticularis
-gondocorticoids(androgens)->sex
within medulla:
adrenal medulla
Adrenal medulla:
●Modified part of the SYMPATHETIC NERVOUS SYSTEM
●Enlarged and specialised sympathetic ganglion
●Secrete catecholamine hormones:
ADRENALINE (epinephrine)
NORADRENALINE (norepinephrine)
●Medulla is chiefly composed of chromaffin cells
●Specialised postganglionic neurons
●Preganglionic = Splanchnic nerve fibres
●Neurotransmitter is acetylcholine
●80% of the medulla secretions is ADRENALINE (epinephrine)
●20% is NORADRENALINE (norepinephrine)
(ADRENAL GLANDS) The major effects of Adrenaline
● Catecholamine release occurs as part of a general sympathetic stimulation
● Important in the FIGHT OR FLIGHT response (fear, anger, stress, excitement etc….)
● Prepares the body for ACUTE STRESS
Cardiovascular effects
*Increases Heart rate and stroke volume
*Increase in blood pressure (systolic)
*Vasodilation of coronary and skeletal muscle blood vessels
*Vasoconstriction of blood vessels to ‘non-essential’ tissues (GIT, skin, kidneys)
*Bronchodilation
Metabolic effects
*Increases the amount of energy for immediate use
*Liver converts glycogen to glucose
*Metabolic rate increases
Blood flow changes, reducing digestive system activity and urine output
(ADRENAL GLANDS)The major effects of adrenal Androgens
action:
●Insignificant amounts of testosterone
●Adrenal glands produce Dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione.
●Testosterone (& Oestrogen) precursors
●Converted to testosterone in peripheral tissues
●Compared to testosterone, DHEA and DHEA-S bind less efficiently to the androgen receptors (weak steroids)
●Controlled by ACTH (anterior pituitary)
effects in males:
●In males, the contribution of testosterone derived from the adrenal glands pales to insignificance in comparison to the normal output of testosterone from the testes
●Role not fully understood
➢Male secondary characteristics
➢Aggression in young boys
● Either over-secretion or under-secretion of adrenal androgens usually does not have any noticeable consequences in males.
effects in females:
●The ovaries make testosterone, but most of it is immediately converted to oestrogen
●In females, the adrenal glands are the primary source of testosterone
●Secrete half the total androgenic requirement
●Responsible for growth of pubic and axillary hair and sex drive
●Kick start puberty
●Maintain muscle and bone mass
excess production of adrenal androgen:
* Overproduction of ACTH, adrenal tumor, Cushing’s syndrome
* Masculinisation of females
* Acne, hirsutism, irregular periods, breast shrinkage…..
* Play a role in polycystic ovary syndrome (PCOS)
Patients with PCOS have adrenal androgen excess
dehydroepiandrosterone (DHEA)
●Apart from providing androgen precursors, it is not clear what other roles, if any, the zona reticularis plays in adult humans.
●DHEA-S is the most abundant circulating hormone in young adults
(ADRENAL GLANDS)Major effects of Mineralocorticoids (aldosterone)
Essential to life – absence leads to circulatory failure & death within a few days if adrenal cortex is removed
Aldosterone secretion is regulated by the plasma levels of sodium and potassium via the renin-angiotensin system (covered in Kidney lectures)
major actions:
Control ECF volume
Conserve body sodium
Stimulates reabsorption of sodium in renal distal convoluted tubules in exchange for potassium
Control of release
Response to renin-angiotensin system (RAAS)
- Decreased ECF volume (hypovolaemia or hypotension) and decreased renal blood flow
- Response to high plasma potassium
(ADRENAL GLANDS)The major effects of Glucocorticoids (cortisol)
Glucocorticoid: Zona Fasiculata
● Wide range of actions; essential to life
● Stress is a powerful stimulator of cortisol production
● Stress = physical trauma, intense heat or cold, infection, mental or emotional trauma
Mediates the body’s response to stress in response to endocrine signals
●Metabolic effects
●Cortisol increases plasma glucose and FFA concentration
●Provide energy substrates to body tissues for their response to the stressful event that stimulated cortisol production
●Increased catabolism: Cortisol increases skeletal muscle protein catabolism. Amino acids are then converted to glucose (gluconeogenesis)
●Increased lipolysis: Liberate free fatty acids & triglycerides from adipose tissue. Used as an energy source
●Increased intake: Stimulates appetite. If the stressful event doesn’t involve physical activity – weight gain
other actions:
●May contribute to emotional instability
●Anti-inflammatory – blocks the processes which lead to inflammation (in high doses)
●Immunosuppressive – fall in antibody production and number of circulating lymphocytes
●Used clinically: to treat patients following transplant
(ADRENAL GLANDS)Control of glucocorticoid secretion
a negative feedback loop:
External conditions can stimulate/inhibit hypothalamus
Hypothalamus releases corticotrophin releasing hormone(CRH)
Targeted for the anterior pituitary gland
Releasing adrenocorticotrophic hormone(ACTH)
Targeted for the adrenal cortex
Adrenal cortex releases cortisol
negative feedback:
ACTH spike causes negative feebdack, inhibiting the hypothalamus
cortisol spike inhibits release from anterior pituitary gland and at the hypothalamus
Secretion of both the glucocorticoids and adrenal androgens are controlled by ACTH secretion
ACTH stimulates enzymes involved in cortisol and
androgen synthesis
Cortisol acts to counteract the effects of stress
Stress: Physical, biochemical and emotional
(ADRENAL GLANDS)Disease states: Adrenal cortex hyperfunction
CUSHINGS SYNDROME
Overproduction of cortisol
●As a result of an adrenal tumour or pituitary tumour
●Redistribution of body fat
●Muscle wastage
●Thin skin, bruising abnormal pigmentation
●Changes in CHO and protein metabolism
●Hyperglyceamia
●Hypertension
●Cortisol has weak mineralocorticoid activity
CONNS DISEASE
* Mineralocorticoid excess
* Rare
* Overproduction of Aldosterone
* Retention of sodium, loss of potassium and alkalosis
Hypertension through expansion of plasma volume
