Endocrine

Endocrine hormones - chemical messengers that travel through circulation to reach distant target cells Paracrine hormones - travel a relatively short distance Autocrine hormones - act on the cells that synthesise and secrete them Juxtacrine hormones - act on the cells in direct contact with them

Peptide hormones Amino acid derivatives Lipid derivatives

Relative short, defined amino acid chains e.g. insulin, glucagon Bind receptors at the plasma membrane Exert their biological effects through plasma membrane receptors

Derived from tyrosine e.g. epinephrine, norepinephrine (catecholamines) and thyroxine and triiodothyronine (thyroid hormones)

Steroid hormones derived from cholesterol e.g. testosterone, oestradiol, progesterone, cortisol, aldosterone Exert their biological effects through intracellular receptors

• Receptors for protein based hormones exist on plasma membranes • Receptors for lipid based hormones exist inside the cell

• Synthesis of the signalling molecule • Release from the signalling cell • Transport to the target cell • Binding to and activation of the target receptor • Transmission of one or more intracellular signals from the activated receptor • Arrival of the message at the final destination of the cell • Changes in cellular function in response to the signal • Termination of the signal and subsequent termination of the cellular response - Binding of hormone to its receptors is non- covalent & reversible

– An extracellular domain (binds hormone) – A membrane spanning region (hydrophobic) – An intracellular domain (interacts with intracellular molecules) Hormone binding causes conformational change of the receptor

– Interacts with and activates a G protein – G proteins interact with and activate plasma membrane enzymes – Activated enzymes catalyse biochemical reactions which result in an increase in a second messenger – The second messenger brings about a cellular response to the hormones signal

Inactive receptors are bound in large protein complexes in the cytosol * Protein complexes contain inhibitor proteins such as Heat Shock Proteins (e.g.HSP90) – Confine the inactive receptors to the cytosol * On binding of the ligand to its homodimeric receptor, inhibitor proteins dissociate * The active receptor translocates to the nucleus * Ligand-receptor complexes bind DNA directly at hormone response elements (HREs) – Regulates gene transcription

Hormones alter the operation of target cells by changing the types, quantities or activities of important proteins – Stimulate the synthesis of proteins not already present in the cell by activation of gene transcription – Increase/decrease the rate of gene transcription and protein translation – Turn on/off an existing protein by modification of its shape or structure (e.g. activation/inactivation of proteins through phosphorylation)

Regulates the neuroendocrine system Central nervous system receives information from internal and external sensors about danger, hunger, diet, blood composition Hypothalamus regulates the production of appropriate hormones by endocrine glands

Stimulus Neuronal response Releasing factors -> hypothalamus Stimulating factors -> pituitary gland Effector hormones -> endocrine gland Response -> target cell

• Hypothalamus secretes a releasing hormone which stimulates hormone production from the pituitary gland • Endocrine hormones produced act on target cells to maintain physiological homeostasis • Once homeostasis is restored hormone production must be reduced Positive or negative feedback

Most common mechanism of hormonal regulation Hormone 1 stimulates production of hormone 2 which feeds back to inhibit cell production of hormone 1

Hormone 1 stimulates production of hormone 2 which stimulates production of hormone 1

LH from pituitary stimulates testis to produce testosterone which feeds back to inhibit LH secretion from the pituitary

LH stimulates ovaries to secrete oestrogen which stimulates LH secretion from the pituitary (surge of LH at ovulation)

• At each level in the signalling cascade, a small signal elicits a much larger response • Hormones are very potent only present in trace amounts • Endocrine systems allow amplification of the initial signal

A process which changes the amount or activity of a hormone results in an endocrine disorder • Overproduction • Underproduction • Resistance to the hormone action

A process which changes the amount or activity of a hormone results in an endocrine disorder • Overproduction • Underproduction • Resistance to the hormone action

Diabetes Mellitus Acromegaly Addison’s disease Cushing’s Syndrome Hyperthyroidism Hypothyroidism Prolactinoma

Increase in growth hormone

Decreased hormones of the adrenal glands