the endocrine system

Question 1

what is intercellular communication

Answer 1

• direct: via gap junctions or direct linkup of cell surface markers
• indirect: via an assortment of chemical messengers or signal molecules

Question 2

what is direct communication

Answer 2

gap junctions: link adjacent cells together
- channels: formed by connexon’s that link the cytosol of adjacent cells permitting transfer of ions between the two cells
- example: gap junctions are crucial to survival in the heart
cell surface markers: complementary surface markers = surface receptors

Question 3

what are indirect chemical messengers / signal molecules

Answer 3

• paracrines, autocrines, cytokines, neurotransmitters and hormones
• process:
  1. secretory cell releases chemical messenger into ECF
  2. messenger binds to specific receptors on the ‘target’ cell
  3. binding of messenger to the receptor triggers a response in the target cell

Question 4

what are paracrines, autocrines, cytokines and neurotransmitters

Answer 4

• P: local, effect neighbouring cells (histamine, epidermal GF, vascular endothelial GF)
• A: self, secreted by cell and then attach to receptor on that cell (growth factors)
• C: immune cells, target cells / circulate in blood (interleukins, interferons)
• N: neurons, short range, synaptic signalling (ACh, dopamine, serotonin)

Question 5

what are hormones and neurohormones

Answer 5

• H: long range, endocrine glands, circulate blood, target cell receptors far from gland, low conc., long lasting effect, slow, integrate activity of cells
• NH: neuro-secretory neurons, similar to neurotransmitters, autocrines and paracrines (vasopressin / ADH)

Question 6

what is the function of the endocrine system

Answer 6

• maintenance of electrolyte, water, nutrient balance of blood (kidney)
• regulation of cellular metabolism and energy balance (insulin) and growth and development (GH)
• mobilisation of body defences (histamine)
• reproduction: secretion of testosterone

Question 7

what are the types of glands

Answer 7

• exo: produce non-hormonal substances, ducts to carry secretion to membrane surface (sebaceous / salivary glands)
• endo: rich vascular / lymphatic drainage, rapid dispersal of hormones, lack ducts (into blood)

Question 8

list the endocrine glands and the hormones they secrete

Answer 8

• pituitary gland: FSH, LH, ACTH, TSH, prolactin, GH
• thyroid gland: T3, T4, calcitonin
• parathyroid gland: PTH
• adrenal glands: aldosterone, cortisol, epinephrine, norepinephrine
• thymus: thymosin
• pineal glands: melatonin
• gonads: progesterone, estrogen, testosterone
• hypothalamus: neuroendocrine organ (exo and endo), ADH, oxytocin, releasing / inhibiting factors

Question 9

describe the mechanisms of hormone action

Answer 9

• must bind to specific receptor
• located in / on cell membrane, in cytosol or in the nucleus
• receptors bind ligands then translate ‘message’ into a cellular response
• involves: activation of transcription factors, increased protein production
• response: activate / deactivate enzymes, induce secretory activity, stimulate mitosis

Question 10

what are receptors and how do they regulate

Answer 10

• amount of receptors on tissues is not static
• amount of hormones influences number of receptors for that hormone
• up regulation: number of receptors increases on the target cell when hormone levels are low
• down regulation: number of receptors decreases on the target cell when hormone levels are high, desensitises cells to prevent overreaction

Question 11

what is a negative feedback system

Answer 11

• controls blood levels of hormones
• increased hormone effects on target organs can inhibit further hormone release
• fluctuation of homeostasis within a narrow / desirable range
• stimuli: hormone triggered by endocrine gland stimuli / NS modulation

Question 12

how is endocrine activity controlled

Answer 12

• rate of production: synthesis / secretion, mediated by +ve and -ve feedback
• rate of delivery: BF to a target organ / cell, high BF delivers more hormone than low BF
• rate of degradation / elimination: characteristic rate of decay (metabolised and excreted differently)
• short half life: stopping secretion = conc. plummets
• long half life: stopping secretion = effects persist for some time

Question 13

what are hydrophilic vs hydrophobic and lipophilic vs lipophobic hormones

Answer 13

• hydrophilic: dissolve in blood, highly water soluble, low lipid solubility, don’t pass through membrane
• hydrophobic: carrier proteins, high lipid solubility, low water solubility, pass through membrane
• lipophilic: hormones diffuse across cell membrane and bind to cytosolic or nuclear receptors
• lipophobic: hormones bind to receptor, causes response element (HRE) in the nucleus, altering gene expression

Question 14

what are surface receptors and the three main types

Answer 14

• proteins that are found attached to the cell membrane and bind to external ligand molecules
• ion channel linked: bind a ligand and open / close a channel, activating receptor enzymes / second messenger systems
• G protein linked: bind ligand (odourant molecules, hormones, neurotransmitters) and activate a membrane protein called a G-protein, cause cAMP signalling or PI signalling (epinephrine, ADH)
• enzyme linked: binding of an extracellular ligand (tyrosine kinases, hormones, GF) causes enzymatic activity on the intracellular side

Question 15

what is cholera

Answer 15

• the downside of g proteins
• transmitted by contaminated water / food
• caused by bacterium Vibrio cholerae, secretion of cholera toxin = choleragen (complex) causes G proteins to stay ‘on’ / activated at all times
• activation ofchloride channel proteins (CFTR), ATP-mediated efflux of chloride ions and leads to secretion of H2O, Na+, K+, and HCO3− into the intestinal lumen
• affects the small intestine and causes violent diarrhoea due to increased water in the gut

Question 16

how is a signal amplified

Answer 16

• very little messenger necessary to bind target cell and cause large effect
• amplification of the initial signal by a second-messenger pathway

Question 17

list the three main classes of hormones

Answer 17

• amino acid base (amino acid or protein / peptide)
• steroids
• eicosanoids

Question 18

what is the pituitary gland

Answer 18

• controls functions of many other endocrine glands
• middle cranial fossa / sphenoid bone
• anterior: larger, glandular tissue, pars tuberalis (sleeve round pituitary stalk), pars distalis (body of gland) and pars intermedia (adjoins posterior lobe), adenohypophysis
• posterior: smaller, neural tissue, infundibulum (connects to hypothalamus) and pars nervosa, neurohypophysis

Question 19

what is the hypothalamus

Answer 19

• integration centre for many physiological processes
• nervous tissue, specialised neurons
• axons: paraventricular, lateral / medial pre-optic and supraoptic axons terminate in posterior lobe
• AP: no direct neural connection, vascular connection (hypophyseal portal system - HPS), releasing / inhibiting factors to AP
• PP: hormones synthesised / secreted from neurons in hyp. travel from hyp. to PP via axons in infundibulum, stored here (ADH and oxytocin)

Question 20

what is human growth hormone (hGH) / somatostatin

Answer 20

• trigger: puberty
• messenger: gHRH / somatostatin (AP)
• cells: somatotroph
• hormone: hGH
• target: all cells
• secondary hormone: insulin like growth factor (IGF)
• secondary target: all cells (esp. muscles / bones)
• function: growth, metabolism, increase blood glucose levels

Question 21

what is LH and FSH

Answer 21

• trigger: puberty
• messenger: gonadotropin releasing hormone (GnRH) (AP)
• cells: gonadotroph
• hormone: LH / FSH
• target: males (leydig cells and sertoli cells) females (ovaries / follicles)
• secondary hormone: male (testosterone / inhibin) female (oestrogen / progesterone)
• secondary target: female (bone, brain, vascular tissue)
• function: sex cell maturation

Question 22

what is TSH

Answer 22

• trigger: cold temperatures
• messenger: thyrotropin releasing hormone (TRH) (AP)
• cells: thyrotrophs
• hormone: TSH
• target: thyroid gland
• secondary hormone: T3 / T4
• secondary target: other cells
• function: increase metabolic rate, carbohydrate, fat and protein metabolism, increase temp (heat production), growth

Question 23

what is ACTH

Answer 23

• trigger: high glucose
• messenger: corticotropic releasing hormone (CRH), fever, hypoglycaemia, stressors (AP)
• cells: corticotrophs
• hormone: ACTH
• target: adrenal cortex
• secondary hormone: cortisol / glucocorticoids
• secondary target: liver
• function: metabolism of fat, protein and carbohydrates, stress response, increase glucose,

Question 24

what is ADH

Answer 24

• trigger: low water (high osmotic pressure) (PP)
• hormone: ADH
• target: kidney (DCT / CT)
• function: conserve water, increase reabsorption of water

Question 25

what is oxytocin

Answer 25

• trigger: childbirth / labour, stretching of uterus (PP)
• hormone: oxytocin
• target: uterus, mammary glands / uterine muscle
• function: uterine contraction, ‘love’ hormone, increase milk expulsion

Question 26

what is prolactin (PRL)

Answer 26

• trigger: breastfeeding
• messenger: prolactin releasing hormone (AP)
• cells: lactotrophs
• hormone: PRL
• target: breast / mammary glands and uterus
• secondary hormone:
• secondary target:
• function: milk production, increased response of follicles

Question 27

what are AA base hormones

Answer 27

amino acid:
- derivatives of single AA
catecholamines / T3/4 (bind to intracellular receptors)
- example: epinephrine
peptide / protein:
- 3-200 amino acids, half lives short (minutes), H2O soluble
- dissolve in extracellular fluid for transport, lipophobic
- hormone-receptor complex initiates response via signal transduction
- example: insulin, parathyroid hormone, angiotensin 2, atrial-natriuretic peptide (ANP)

Question 28

what are steroid base hormones

Answer 28

• all synthesised from cholesterol (gonadal and adrenocortical hormones)
• lipophilic (diffuse easily across membranes), no storage in secretory vesicles (continual synthesis)
• poorly soluble in blood (carrier proteins = albumin)
• example: gonadal hormones (oestrogen, testosterone), aldosterone and cortisol

Question 29

what are eicosanoid base hormones

Answer 29

• hormone like, paracrine (only in vicinity of gland secreting it)
• hormone like compounds: formed from polyunsaturated fatty acid (18, 20, 22 carbons)
• synthesised throughout body, autocrine / paracrine actions (effects cell which secretes it)
• example: prostaglandins, thromboxanes and prostacyclin

Question 30

what is the HPS (hypophyseal portal system)

Answer 30

• neurons in hypothalamus terminating close to capillaries within hypothalamus release hormones into HPS
• circulate anterior pituitary through HPS
• anterior relieves hypothalamus hormones (releasing / inhibiting factors) and regulates secretion of other hormones

Question 31

what is the structure / hormones of the thyroid gland

Answer 31

• ventral / anterior surface of trachea, two lateral lobes, connected via isthmus lobes, one pyramidal lobe (top), butterfly shaped
• BS: superior / inferior thyroid arteries
• principal / follicular cells: formation of colloid, line follicle cells
• follicle cells: simple cuboidal epithelium, contains colloid
• colloid: gelatinous mixture made of thyroglobulin (stores thyroid hormones)
• parafollicular cells (c cells): loose connective tissue, scattered, delicate, between follicles in basal lamina, produce calcitonin
• T3: lipophilic, bind to thyroid hormone receptor, 3 iodine molecules, 0.4% is free
• T4: lipophilic, bind to thyroid hormone receptor, main, 4 iodine atoms, 99.98% bound to 3 serum proteins (75% globulin, 15-20% pre albumin, 5-10% albumin), 0.02% unbound / free

Question 32

what is the parathyroid gland

Answer 32

• S: 4 glands, posterior to thyroid, different structures and function, larger cells
• F: releases PTH in response to low plasma Ca
• increases Ca in body by kidneys (increases reabsorption / production of vitamin D / calcitrol), calcitrol (increases GI absorption), uses Ca from bones

Question 33

what are the adrenal glands

Answer 33

• structure: both cortex (outer) and medulla (inner) have an endocrine function but different hormones
• location: above the kidneys

Question 34

how does the synthesis of thyroid hormones occur

Answer 34

• iodine: iodised salt, dairy products, shellfish (absorbed in GI tract)
  1. TSH secreted from AP (stimulates TH secretion)
  2. iodide actively transported into thyroid follicle cells via co-transport (Na/I system) and oxidised to iodine by peroxide
  3. thyroglobulin (Tg) is synthesised in follicle cell
  4. one (monoiodotyrosine) or two (diiodotyrosine) iodine atoms bind to tyrosine molecules of thyroglobulin via thyroid peroxidase
  5. Tg is exocytosed into the follicle lumen
  6. 2 x diiodotyrosine’s bind to form T4 or 1x diiodotyrosine and 1x monoiodotyrosine to form T3 (stored as Tg)
  7. Tg taken into thyroid follicle cells via endocytosis

Question 35

describe the steps in regulation of thyroid hormones

Answer 35

1. TRH from hyp. through portal blood vessels to AP
2. TSH is released
3. TSH binds to surface receptors in thyroid, stimulates adenylate cyclase to produce cAMP
4. TSH increases metabolic activity required to synthesise Tg and generate peroxide
5. TSH acts on follicular cells of thyroid, increasing iodide transport into follicular cells and production / iodination of thyroglobulin
6. increases endocytosis of colloid from lumen into follicular cells
7. TSH binds to a G protein-coupled receptor on thyroid follicle membrane
8. specifically activates a G-coupled receptor, increased cAMP production and protein kinase A (PKA) activation

Question 36

what is hyper / hypo thyroidism

Answer 36

hyper: high
- graves disease: autoimmune, production of too much TH
- symptoms: high BMR, tachycardia, weight loss, anxiety, sweating, diarrhoea, insomnia, swelling of the neck (goitre), exophthalmos (protruding eyes)
- histology: bubbles in hyperthyroidism tissue sections
- treatment: thyroidectomy (partial / total), antithyroid drugs
hypo: low
- hashimoto’s disease: autoimmune, under active, not enough T3 / T4
- symptoms: low BMR, brachycardia, weight gain, reduced sweat, constipation, lethargy, myxoedema (swelling of face and body), more common in females (x5)
- treatment: hormone replacement (TH tablets)

Question 37

what are corticosteroids

Answer 37

• actions: anti inflammatory, allergy and immunity (synthetics used)
• hydrocortisone: oral replacement, IV for shock and asthma, topically for eczema and ulcerative colitis
• prednisolone: widely used orally in inflammation and allergic diseases
• side effects: raised BP, fluid retention (leg swelling) and weight gain
• long term: cataracts, diabetes, osteoporosis, fractures, bruising, cancer
• cushing’s syndrome: excess glucocorticoids, rapid weight gain, flushed skin, ‘moon face’, hyperglycaemia, high BP, poor wound healing, osteoporosis, muscle wastage and depression
• addison’s disease: insufficient steroid hormones, rare, primary / chronic insufficiency, weight loss, hyper-pigmentation, fatigue, hyponatremia, hyperkalaemia

Question 38

what is the adrenal medulla

Answer 38

• short term stressor response (fight or flight / rapid)
• catecholamines: produces epinephrine / norepinephrine, secreted from chromaffin cells, prepare for short term stress, stored in electron-dense granules, stimulated by ACh
• effect: mimic sympathetic NS, increase plasma glucose, HR and contraction force (cardiac output), increase BP, metabolic function, bronchodilator, decreased GI / urinary function
• stimulation: pre-ganglionic fibres of the sympathetic NS, less than 30 seconds to kick in and lasts several minutes

Question 39

what is the function of the thyroid gland

Answer 39

• normal development of musculoskeletal system and brain development
• BMR: increased use of O2 by cells to make more ATP, increased ATP increases fuel use (carbohydrates and lipids), protein synthesis increases
• heat production: increased production of Na/K ATPase (pump), when active, enzyme releases heat due to ATP breakdown

Question 40

what is calcitonin vs calcitrol

Answer 40

• calcitonin: reduces Ca in body, increases bone uptake, decreases renal and GI reabsorption (into bone)
• calcitrol: increases Ca in body, decreases bone uptake, increases renal and GI reabsorption (out of bone)

Question 41

what is the adrenal cortex

Answer 41

• long term stress response (required for survival / immunosuppression)
• structure: zona glomerulosa (aldosterone), zona fasiculata (cortisol), zona reticularis (androgen)
• mineralocorticoids (aldosterone): stimulated by RAAS, steroid, target kidney, increase Na reabsorption and K and H secretion, water reabsorption, increase BP / BV
• glucocorticoids (cortisol): steroid, targets tissues, increased protein / lipid breakdown, increased glucose production, inhibition of immune response, decreased inflammation, increase AA transport to liver (reduce protein storage in all cells except liver), decrease Ca
• androgens: steroid, targets tissues, development of secondary sex characteristics (females)

Question 42

what is the pancreas

Answer 42

• S: 15-20 cm long, head, neck, body and tail
• L: retro-peritoneum
• F: exocrine function (digestive), regulating blood glucose (endocrine function)
• H: islets = relatively pale staining population, extremely rich capillary supply, 25% glucagon cells (alpha), 60% insulin cells (beta), 10% somatostatin cells (delta) and gherlin e cells
• islets of langerhans: beta cells occupy central portion surrounded by ‘rind’ of alpha / delta, receive 15% of blood
• adults: ~2000-3000 β cells, ~1 million islets scattered throughout pancreas

Question 43

what is glucagon vs insulin (immunohistochemistry)

Answer 43

• G: low blood glucose, sympathetic NS triggers release of glucagon from alpha cells, glucose releases into blood via glucogenesis and glycogenolysis
• I: high blood glucose, parasympathetic NS triggers release of insulin from beta cells, glucose uptake from blood via glycogenesis (storage) and promotes glycolysis

Question 44

describe insulin in detail

Answer 44

• peptide hormone
• S: insulin mRNA translated as a single chain precursor (pre-proinsulin) and removal of signal peptide = pro-insulin (86 AA)
• F: acts on tissues (liver, skeletal muscle, adipose) to increase uptake of glucose and AA, increases glycogen production, stimulates lipid synthesis, glucose into cells, intermediary metabolism
• beta (rest):
  1. low glucose in blood
  2. metabolism slows decreasing ATP production
  3. KATP channel opens and K leaks out of cell
  4. resting membrane potential
  5. voltage gated Ca channels closed no insulin secretion
• beta (secreting)
  1. high glucose in blood
  2. increased glycolysis and citric acid cycle increasing ATP production
  3. KATP channel closed and less K leaves the cell
  4. depolarising membrane
  5. voltage gated Ca channels open, presence of Ca triggers exocytosis, insulin secreted
• stimuli: increased BG, AA, keto acids, neural stimuli, inhibited by stressors
• immediate response

Question 45

describe glucagon in detail

Answer 45

• S: 29 AA polypeptide, potent hyperglycaemic agent
• synthesis: as pro-glucagon, proteolytically processed to yield glucagon within alpha cells of pancreatic islets
• F: promotes breakdown of glycogen in the liver, synthesis of glucose gluconeogenesis), breakdown of adipose (fat) and release of fatty acids
• regulation: increased blood glucose levels / insulin inhibit, AA stimulate glucagon release, gluconeogenesis and lipolysis
• stress (epinephrine - beta-adrenergic receptors on alpha cells increase release)

Question 46

what is somatostatin (SS)

Answer 46

• F: inhibiting secretions of hGH, acts as a paracrine, inhibits insulin / glucagon
• injection into rodent brains increase arousal, decrease sleep and impairment of motor responses
• treat gigantism and acromegaly (inhibits hGH)
• hGH secretion: ultimately controlled by interaction of SS and GHRH

Question 47

describe blood glucose regulation in summary

Answer 47

• organs: liver (makes and exports glucose) and pancreas (releases insulin and glucagon)
• parasympathetic NS: stimulates insulin secretion
• sympathetic NS: stimulates glucagon
• insulin: increase glucose oxidation, increase glycogen, fat and protein synthesis
• glucagon: increase gluconeogenesis, glucogenolysis and ketogenesis (lipolysis etc)

Question 48

what is type 1 diabetes

Answer 48

• insulin dependent diabetes mellitus (IDDM)
• cause: immune system destroys beta cells (no insulin), hyperglycaemia (glucose cannot enter adipose cells)
• symptoms: polyuria, polydipsia, polyphagia, diabetic retinopathy, neuropathy, diabetic neuropathy (damage to nerves), myocardial infarction / stroke, circulatory problems (gangrene / foot problems)
• treatment: insulin delivery injections daily, glucose monitors and insulin pumps
• transplant: benefits (reduces hypoglycaemia / complications, good glycemic control), limitations (shortage of islets, immune suppressive therapy, high costs, long-term insulin dependence)
• stem cell treatment: success in some but not all, costly, immune rejection, IPSC / ESC - precursor cell - beta cell

Question 49

what are the appetite and hunger hormones

Answer 49

• leptin: mediator of long-term regulation of energy balance, decreaseshunger, secreted primarily from adipose tissue, some obese patients are leptin-resistant
• ghrelin: fast-acting hormone, secreted primarily in stomach lining when stomach is empty, produced in E cells of pancreas, plays a role in meal initiation, increases hunger