Lecture 5.1 - Introduction to the endocrine system and the endocrine pancreas

Steroid Hormones and Energy Balance

• C21 steroids: corticosteroids (glucocorticoids, e.g., cortisol, and mineralocorticoids, e.g., aldosterone) and progestins (e.g., progesterone from ovaries)
• C19 steroids: androgens (e.g., testosterone from testes)
• C18 steroids: oestrogens (e.g., oestradiol from ovaries)

Hormone Action

• Hormones act by binding to receptors on or in target cells
• Magnitude of response depends on: hormone concentration, receptor number, hormone-receptor affinity, and signal amplification
• If hormone cannot cross membrane, it binds to cell surface receptor, activates second messenger pathway, and exerts metabolic effects

Mechanism of Action of Steroid Hormones

• Steroid hormones bind to receptors in target cells, leading to changes in gene expression and protein synthesis

Control of Energy Balance

• Energy balance: energy intake = expenditure (stable body weight), energy intake > expenditure (increased energy stores), energy expenditure > intake (decreased energy stores)
• Appetite control centre: hypothalamus, containing clusters of neurons (nuclei), including the arcuate nucleus

Control of Appetite

• Arcuate nucleus contains two types of neurons: primary (sense glucose, fatty acids, and hormones) and secondary (integrate signals for feeding behavior)
• Primary neurons: stimulatory (excitatory, containing NPY and AgRP) and inhibitory (containing POMC, alpha-MSH, and beta-endorphin)
• Ghrelin: released from stomach wall when empty, stimulates appetite, and inhibited by stomach distension
• PYY (Peptide tyrosine tyrosine): released from ileum and colon in response to feeding, inhibits appetite, and signals satiety

Hormonal Signals

• Leptin: released from fat cells, suppresses appetite, and stimulates POMC neurons in the arcuate nucleus
• Insulin: suppresses appetite by similar mechanism as leptin
• Amylin: secreted by pancreatic beta cells, suppresses appetite, decreases glucagon secretion, and slows gastric emptying

Other Players and Therapeutics

• Large intestine: oxyntomodulin, GLP-1
• Small intestine: cholecystokinin, GIP
• Adipose: adiponectin, resistin, visfatin
• Pancreas: PP (Pancreatic polypeptide)

Integration of Energy Balance

• Leptin: discovery, role in energy balance, and response to injection in leptin-deficient individuals

Pancreas

• Anatomy: retro-peritoneal gland, majority exocrine, highly vascular and innervated
• Development: embryological origin from the foregut, similar to the brain
• Exocrine function: 98-99% secretion of enzymes for digestion of lipids, carbohydrates, and proteins
• Endocrine function: 1-2% of pancreatic mass, hormone production

Homeostasis

• Control centre: hypothalamus, determines reference set point
• Receptor: sensors detect changes in the environment
• Effector: agents cause change
• Feedback: output affects the control centre

Endocrine Hormones

• Definition: chemical signals produced in endocrine glands or tissues that travel in the bloodstream to cause an effect on other tissues
• Release: from endocrine glands, travel in blood stream, interact with receptors, and cause coordinated responses

Glands of the Endocrine System

• Endocrine tissue: pancreas, thyroid, adrenal glands, etc.
• Biologically active chemical: hormones produced by endocrine glands
• Transport: in blood stream
• Target cells: receptors and response
• Inactivation: metabolism of hormone causes inactivation

Control of Hormone Secretion

• Rate of secretion usually controlled by negative feedback: change in parameter regulated by the hormone or concentration of hormone itself or another hormone

Hormone Concentrations

• Hormones circulate in very low concentrations (e.g., thyroxine 10-30 pmol/L)