E1

• Endocrinology

  Study of HORMONES
• Hormone

  Substance secreted directly into the blood by specialised cells
• Hormones are present in only minute concentrations in the blood and bind specific receptors in target cells to influence cellular reactions
• Endocrine glands

  • Hypothalamus
  • Pituitary
  • Thyroid
  • Parathyroids
  • Adrenals
  • Pancreas
  • Ovary
  • Testes
• Endocrine organs

  • Heart
  • Liver
  • Intestines
  • Kidney
  • Skin
• Actions of hormones

  • Foetal development
  • Cell growth and cancer
  • Metabolism
  • Cardiovascular function
  • Renal function
  • Skeletal function
  • Reproductive function
  • Immune function
  • CNS function
• How hormones affect us

  • Pre-menstrual tension
  • Pregnancy- post natal depression
  • Puberty
  • High dose steroids- psychosis
  • Hypogonadism- poor libido
  • Insulinoma- behaviour
• Hormone- basic actions

  • Thyroid- BMR, growth
  • Parathyroid- Ca regulation
  • Cortisol- glucose regulation, inflammation
  • Aldosterone- BP, Na regulation
  • Catecholamines- BP, stress
  • Oestradiol- Menstruation, femininity
  • Testosterone- sexual function, masculinity
  • Insulin- glucose regulation
  • Vitamin D- Ca regulation
• The endocrine system maintains homeostasis- feedback mechanism- usually negative
• Regulate wide variety of biological processes
• Major endocrine glands

  • pituitary
  • adrenal
  • thyroid
  • parathyroid
  • pancreas
  • ovary
  • testes
• Hormones

  • Signalling molecules
  • Steroids- e.g. thyroid and sex steroids (oestrogen)
  • Neurotransmitters- e.g. noradrenaline
  • Growth factors and cytokines- e.g. epidermal growth factor
  • Fatty acid derivatives- peroxisome proliferator activated receptors
• Hormone super families

  • Peptide hormones
  • Steroid hormones
  • Amino acid derivatives
• Peptide and proteins hormones

  • Storage- day
  • Secretion by exocytosis
  • Some Binding protein
  • Half-life= min-hour
  • Time to action= min-hour
• Steroids and pseudo steroids hormones

  • Storage- min-hour
  • Secretion by diffusion
  • All Binding protein
  • Half-life= hours
  • Time to action= hour-day
• Thyroid hormones

  • Storage- weeks
  • Secretion by proteolysis
  • Binding protein
  • Half-life= days
  • Time to action= day
• Catecholamines

  • Storage- day
  • Secretion by exocytosis
  • No binding protein
  • Half-life= sec-min
  • Time to action= sec
• Peptide/protein hormones

  • Size= From 10-20 amino acids to 100s
  • Water soluble
  • Compromise the largest number of hormones
  • Produced as larger molecular weight precursors that are proteolytically cleaved to the active form of the hormone
• Protein hormone storage

  1. In vesicles or granules

  2. Signal-> released form cell by exocytosis
• Polypeptide hormone synthesis and release

  1. mRNA on the ribosomes of the ER binds aa into a peptide chain called a 'preprohormone'

  2. Chain is directed into ER lumen by a signal sequence of aa

  3. Enzymes in the ER chop off the signal sequence= inactive prohormone

  4. prohormone passes from the ER through the Golgi apparatus

  5. secretory vesicles containing enzymes and prohormone bud off the Golgi

  6. enzymes chop the prohormone into 1 or more active peptides plus additional peptide fragments

  7. secretory vesicle releases its contents by exocytosis into the extracellular space

  8. the hormone moves into the circulation for transport to its target
• Prohormones

  • Protein hormone precursors
  • Part of preprohormone
  • preprohormone- consists of signal peptide, inactive fragment and prohormone
  • Allows fine-tuning of hormone activation
  • prohormone-> active hormone requires an addition enzyme that can be localised around target tissue
• Generating ACTH

  1. synthesised in the pituitary gland

  2. pre-pro-opiomelanocortin- signal peptide remove during translation, consists of γ-MSH, ACTH, β-lipotropin

  3. add prohormone convertase= ACTH-> α-MSH and CLIP

  4. add prohormone convertase= β-lipotropin-> γ-lipotropin and β-endorphin

  5. y-lipotropin-> β-MSH
• Insulin

  C chain serves as linker between the A- and B chains of insulin and facilitates efficient assembly, folding an processing of insulin
• Amino acid derivatives

  • Thyroid hormones synthesised from tyrosine in the thyroid gland
  • T4 contains 4 iodine resides- only known need for iodine in the diet
  • Metabolised to more active T3 (TR α, β and splice variants)
• Synthesis of thyroid hormones

  1. Thyroglobulin is synthesised and discharged into the follicle lumen

  2. Iodide is actively transported in- trapped

  3. Iodide is oxidised to iodine

  4. Iodine is attached to tyrosine in colloid, forming DIT (T2) and MIT (T1)

  5. Iodinated tyrosines are linked together to form T3 and T4

  6. Thyroglobulin colloid is endocytosed and combined with a lysosome

  7. Lysosomal enzymes cleave T4 and T3 from thyroglobulin colloid and hormones diffuse into blood stream
• Thyroid hormones are stored until they are needed
• Steroid hormones and other small molecules

  • Easily pass through PCM- bec steroids= lipophilic
  • Included glucocorticoids and sex hormones, thyroid hormone and vitamin D
  • Steroids are not stored- they are produces on demand
  • All steroids are made from cholesterol
• Biosynthesis of steroid hormones

  1. Mineralocorticoid- SALT

  2. Glucocorticoid- SUGAR

  3. Androgens- SEX

  4. Start with CHOLESTROL- Therefore cholesterol formation is a rate limiting step (this happens in mitochondria)
• Steroid hormone synthesised from cholesterol in adrenal and gonads
• Cholesterol is transported into the mitochondria by StAR (rate limiting step)