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

Protein/peptidehormones

Steroidhormones(cholesterol)

Amino acidderivatives

Fatty acidderivatives

Hypothalamichormones

CortisolAldosterone

AdrenalineNor-adrenaline(tyrosine)

ProstaglandinsThromboxanesProstacyclin

Pituitaryhormones

OestrogensAndrogensProgestagens

Thyroidhormones(tyrosine)

InsulinPTHCalcitonin

Vitamin D Melatonin(tryptophan)

Chemical nature of hormones

Chemical nature of hormones and their transport

Hormone Half life incirculation

Transport

Amino acidderivatives

Minutes Mainly unbound

Tyrosinederivatives –CA’s, thyroidhormones

Seconds (CA’s)Hours (thyroidhormones)

Thyroidhormones boundto plasmaproteins

Cholesterolderivatives – allsteroids

Hours - days Bound to plasmaproteins

Hormone synthesis

• Peptides and proteins

Water soluble, made from large precursor molecules - prohormones.

• Steroids and iodinated tyrosinesLipid 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 Glands controlled by the hypothalmic-pituitary

axisaxis

Hypothalamus

Pituitary gland

Thyroid Adrenal cortex Gonads

Releasing/inhibiting neurohormones

Trophic hormones

TSH ACTH LH/FSH

Feedback control of hormone synthesis

Increase in controlled variable

Decrease in controlled variable

Feedback control in the endocrine system

PancreasParathyroid

Hypothalamus

Pituitarygland

Peripheral target gland

Blood glucoseCa2+

Sh

ort

loop

Lon

g lo

op

SteroidsThyroid hormones

GH/PRL

Feedback control of thyroid hormone

synthesis and release

Rhythms in hormone secretions

• All hormones secreted in a pulsatile pattern

• Daily rhythms :

CircadianDiurnal

• 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 hormonesCushing’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