An introduction to the endocrine system Discovery of hormones Classification of hormones and general functions of hormones Major endocrine glands Feedback control of hormone secretions Rhythms in hormone secretions Mechanisms of endocrine disorders Endo 1: When, what and where

Mans first endocrine experiment and his first attempt at biological warfare? 350 BC Aristotle records how camels were mutilated for ‘war’ purposes - it prevented pregnancy and copulation during battle

Landmarks in the discovery of hormones  Animal castrations  1849 Berthold – testicular grafts  1849 Addison – diseases of the adrenal glands  1889 Brown-Séquard – rejuvenating organotherapy  1891 Murray – extracts of thyroid gland relieved symptoms associated with myxoedema  1894/95 Oliver and Schäfer – vasopressive effects of adrenal and pituitary extracts  1900’s – Internal secretions  1902 Bayliss and Starling discovered secretin.  Term hormone (from Greek meaning to “stir up” was introduced

Major endocrine glands Hypothalamus - releasing and inhibiting hormones Pituitary gland - trophic hormones: oxytocin and vasopressin Thyroid, adrenal cortex, gonads Pancreas Parathyroid glands

Major endocrine glands and their secretions HYPOTHALAMUS - Releasing & inhibiting hormones PITUITARY GLAND - Trophic hormones, oxytocin/vasopressin (ADH) THYROID GLAND - Thyroxine, tri-iodothyronine ADRENAL GLAND - Cortex: Cortisol, aldosterone Medulla: Adrenaline/noradrenaline GONADS - Oestrogens, androgens, progestagens PANCREAS - Insulin, glucagon PARATHYROID GLAND - Parathyroid hormone OTHERS - Kidney (Vit. D, EPO): CVS (ANP, endothelins) pineal gland (melatonin): thymus gland (thymic hormones)

GENERAL FUNCTIONS OF HORMONES Reproduction, growth and development Sex Steroids, thyroid hormones, prolactin, growth hormone Maintenance of internal environment Aldosterone, parathyroid hormone, vitamin D Energy production, utilization and storage Insulin, glucagon, thyroid hormones, cortisol, growth hormone

Chemical Classification of hormones

Chemical nature of hormones

Chemical nature of hormones and their transport

Hormone synthesis Peptides and proteins Water soluble, made from large precursor molecules - prohormones. Steroids and iodinated tyrosines Lipid soluble, made from low molecular weight precursors Peptides - secretory granules, RER. Steroids - lipid droplets

Structure of growth hormone and prolactin

Structure of thyroid hormones derived from tyrosine

Steroid synthesis from cholesterol

INTRACRINE AUTOCRINE PARACRINE ENDOCRINE NEUROENDOCRINE HORMONAL/ CHEMICAL SIGNALLING

Glands controlled by the hypothalmic-pituitary axis Hypothalamus Pituitary gland ThyroidAdrenal cortexGonads Releasing/inhibiting neurohormones Trophic hormones TSHACTHLH/FSH

Feedback control of hormone synthesis Increase in controlled variable Decrease in controlled variable

Feedback control in the endocrine system Pancreas Parathyroid Hypothalamus Pituitary gland Peripheral target gland Blood glucose Ca 2+ Short loop Long loop Steroids Thyroid hormones GH/PRL

Feedback control of thyroid hormone synthesis and release

Rhythms in hormone secretions All hormones secreted in a pulsatile pattern Daily rhythms : Circadian Diurnal Monthly cycles Annual cycles

Ovarian cycles - days a) Pulsatile rhythm of LH secretion b) Diurnal (sleep-related) rhythm of prolactin secretion c) Fluctuating hormone secretions during oestrous or menstrual cycles of mammals d) Annual rhythms of sex hormones seen in seasonal breeders

a) The sleep related rise in growth hormone (GH) secretion that does not occur when the normal light/dark cycle is disturbed (b) c) Endogenous circadian rhythm of cortisol secretion that will run irrespective of the light dark cycle, but without entrainment

Diurnal rhythms of prolactin and growth hormone

The pulsatile pattern of LH (and other hormones such as growth hormone) can vary throughout life

Disorders of the Endocrine System Excess or deficiency Impaired synthesis Transport and metabolism of hormones Resistance to hormone action

Excess growth hormone acromegaly Gross hypothyroidism

Addison’s disease - deficiency of adrenocortical hormones Cushing’s disease - excess glucocorticoids

Disorders of the Endocrine System Excess or deficiency Impaired synthesis Transport and metabolism of hormones Resistance to hormone action

Complete resistance to circulating androgens - testicular feminization Vitamin D resistant Rickets