hormones

Question 1

Explain endocrine system and hormone action

Answer 1

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

Question 2

 Chemical nature and mechanism of action of hormones

Answer 2

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

Question 3

Endocrine-negative feedback

Answer 3

*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

Question 4

(PITUITARY GLAND) Location & structure

Answer 4

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

Question 5

 (PITUITARY GLAND) posterior lobe

Answer 5

*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

Question 6

 (PITUITARY GLAND) anterior lobe

Answer 6

‘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

Question 7

 (PITUITARY GLAND)anterior pituitary- Relationship with the hypothalamus

Answer 7

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

Question 8

(PITUITARY GLAND) The role of growth hormone (GH)

Answer 8

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

Question 9

(PITUITARY GLAND)Disease states associated with GH

Answer 9

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

Question 10

 (THYROID GLAND)Position and structure

Answer 10

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

Question 11

 (THYROID GLAND)Structure and synthesis of triiodothyronine (T3) and thyroxine (T4)

Answer 11

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

Question 12

 (THYROID GLAND)Thyroid hormone synthesis

Answer 12

Triiodothyronine (T3) and thyroxine (T4)
Synthesis requires 2 principle raw materials:

1. Tyrosines
   Provided by thyroglobulin
   Secreted by follicular cells into lumen of follicle as colloid
2. 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

Question 13

 (THYROID GLAND) Major physiological effects of T3 & T4

Answer 13

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

Question 14

(THYROID GLAND) regulation of thyroid hormone secretion

Answer 14

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

Question 15

 (THYROID GLAND) Disease states-hypothyroidism

Answer 15

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

Question 16

 (THYROID GLAND) Disease states-hyperthyroidism

Answer 16

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

Question 17

(ADRENAL GLANDS)Position and structure of both the outer cortex and inner medulla

Answer 17

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)

Question 18

(ADRENAL GLANDS) The major effects of Adrenaline

Answer 18

● 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

Question 19

 (ADRENAL GLANDS)The major effects of adrenal Androgens

Answer 19

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

Question 20

dehydroepiandrosterone (DHEA)

Answer 20

●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

Question 21

(ADRENAL GLANDS)Major effects of Mineralocorticoids (aldosterone)

Answer 21

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

Question 22

 (ADRENAL GLANDS)The major effects of Glucocorticoids (cortisol)

Answer 22

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

Question 23

 (ADRENAL GLANDS)Control of glucocorticoid secretion

Answer 23

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

Question 24

(ADRENAL GLANDS)Disease states: Adrenal cortex hyperfunction

Answer 24

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

Question 25

 (ADRENAL GLANDS) Disease states: Adrenal cortex hypofunction

Answer 25

ADDISONS DISEASE
●Rare
●Damage to adrenal glands, autoimmune disease or pituitary damage
●Deficits in glucocorticoids and mineralocorticoids
●Progressive weakness, lassitude and weight loss
●Pigmentation of the skin and mucosal membranes

Question 26

(PLASMA CALCIUM) Major function of Ca2+

Answer 26

*Structural component of bones and teeth (99% total calcium)
*Maintains normal excitability of nerve and muscle cells
*Involved in neurotransmitter and hormone release
*Muscle contraction (skeletal and cardiac)
*Activation of many enzymes
*Coagulation of blood
Milk production

Question 27

(PLASMA CALCIUM)  plasma Ca2+ concentration/forms

Answer 27

In nature:does not exist freely(occurs in limestone)
In body: most abundant mineral approx. 1kg - 1% in the cell, 0.1% in extra cellular fluid(ECF), Rest in skeleton-hydroxyapatite

plasma calcium levels:
Plasma calcium concentration is 2.2-2.6mM
1) Protein-bound calcium
2) Ionized or free calcium
3) Complexed or chelated calcium

Protein-bound calcium cannot diffuse through membranes and thus is not usable by tissues

Ionized or free calcium is the physiologically active form

Complexed or chelated calcium is bound to phosphate, bicarbonate, sulfate, citrate, and lactate

Question 28

(PLASMA CALCIUM) hypo/hypercalcemia

Answer 28

hypocalcemia:
Too low: Involuntary muscle contraction
Neuronal hyper-excitability (tetany)
Low ionized calcium levels in the extracellular fluid increase the permeability of neuronal membranes to sodium ion, causing a progressive depolarization, which increases the possibility of action potentials

hypercalcemia:
Too high: depression & kidney damage/stones
Neurons less excitable

control points for calcium:
Absorption – Via intestines
Excretion – Via Kidney/urine
Temporary storage – Via bones

bone dynamics:
Osteoblasts
*Synthesize and secrete collagen and promote deposition of calcium phosphate crystals. Secrete factors that activate osteoclasts
Osteoclasts
*Promote resorption of bone
Osteocytes
Essential role in exchange of calcium between ECF and bone

Question 29

(PLASMA CALCIUM) calcium regulation, concentration determination,

Answer 29

regulation:
Acute control
*Must maintain constant free Ca2+ concentration in the plasma
*Mostly by rapid exchange between bone and ECF
Chronic control
*Maintain total level in the body long term
*Adjust GIT absorption and urinary excretion

concentration determination
Net absorption of Ca2+ from the GIT
Net excretion of Ca2+ in urine
Exchange of Ca2+ with bone

Controlled by 3 hormones (in order of importance)
1) Parathyroid hormone
2) 1,25-dihydroxycholecalciferol -> calcitriol -> activated Vitamin D
3) Calcitonin

Question 30

(PLASMA CALCIUM)Functional role of: Parathyroid hormone

Answer 30

PTH gland monitors the concentration of calcium in the blood perfuming the glands

Peptide hormone
Stored within the chief cells
Half life of 5 minutes
Secreted continuously at a low rate
Released in response to low blood calcium
Exerts it effects on bone, gut and kidneys

Main target tissue is the kidney and bone
reabsorption of calcium from the urine
Fast acting; urinary calcium in minutes
the expression of the enzyme 1α-hydroxylase (activates vitamin D)
Bone: osteoclast activity (Indirectly)causing in bone resorption

Question 31

(PLASMA CALCIUM)Functional role of: Vitamin D

Answer 31

Vitamin D2 (Ergocalciferol): Plant sources
*Vitamin D3(Cholcalciferol): Obtained from the diet (animal sources), food supplements and synthesised in the skin in the presence of sun light
*D2 & D3 relatively inactive.
*Converted to 1,25 dihydroxycholecalciferol
*AKA: 1,25-dihydroxyvitamin D
*AKA: 1,25-(OH)2D3
AKA: Calcitriol

Question 32

(PLASMA CALCIUM)actions of: Calcitriol

Answer 32

Acts on cells on the GIT to increased production of calcium transport proteins
Leads to an increase in Calcium uptake from GIT
The only mechanism that can increase calcium stores
Bone: Increasing rate of bone resorption
Increases the secretion of osteoclast activating factors (Indirect effect)
Kidney: Minor effect in decreasing urinary loss of calcium

Question 33

(PLASMA CALCIUM)Functional role of: Calcitonin

Answer 33

Secreted by the C-cells (parafollicular cells) of the thyroid gland. Minor importance in adults.
Lowers the level of free plasma calcium
Inhibition of osteoclast activity: bone resorption reduced (direct effect)
Increased excretion of calcium and phosphate by the kidneys

Question 34

other hormones involved in plasma calcium regulation:

Answer 34

Major hormonal regulators: PTH, 1,25-(OH)2D3, and possibly calcitonin
Others:
➢Growth hormone, adrenal glucocorticoids & thyroid hormones
➢Oestrogen and androgens

Question 35

plasma calcium disorders
Hyperparathyroidism = HYPERCALCAEMIA

pathalogical reasons:

Answer 35

Inappropriate (autonomous) secretion of PTH, resulting in HYPERCALCAEMIA
Elevated PTH and raised serum calcium (& low serum phosphate)
85% of cases are caused by a single parathyroid adenoma
Presentation: Bones, stones, abdominal groans and physical moans
Increase bone reabsorption
Increased GIT absorption
Decreased renal excretion

Question 36

plasma calcium disorders

Vitamin D deficiency = HYPOCALCAEMIA

Answer 36

in children: rickets
Bone remodeling impaired
Failure of calcification
Rickets: Skeletal deformities of weight bearing bones in children

Vitamin D deficiency due:
Poor diet
Malabsorption
Decreased sunlight
Liver or kidney disease

adults: osteomalacia

●Hypocalaemia leads to increased excitability of nervous tissue
●Pins and needles, tetany, muscle cramps, convulsions
●Vitamin D deficiency leads to reduction in intestinal calcium absorption
●Is hypocalcaemia in vitamin D deficient patients likely to become severe?
No-compensatory rise in PTH-calcium taken from the bone stores