S2 L1 Physio

Introduction to Endocrine Physiology

• Endocrine physiology is the study of the hormonal control systems in the body
• Hormones are secreted from groups or single cells
• Hormones regulate various functions like chemical reactions, transport of substances, growth and development, water and electrolyte balance, and secretion

Learning Objectives

• Classify hormones by structure
• Describe hormone synthesis, secretion, and transport
• Explain the mechanism of hormone action

Nature of Hormones

• Some hormones act locally (e.g., acetylcholine)
• Some hormones act on all cells (e.g., growth hormone)
• Other hormones act on specific target tissues (e.g., adrenocorticotropic hormone on adrenal cortex)

Principle Endocrine Glands

• Pituitary gland
• Hypothalamus
• Pineal gland
• Thyroid gland
• Parathyroid glands
• Thymus gland
• Pancreas
• Kidney
• Ovaries
• Testes
• Adrenal glands
• Adipose tissue
• Stomach
• Small intestine

Chemical Structure of Hormones

• Protein/polypeptide hormones (e.g., anterior and posterior pituitary, pancreatic hormones)
• Steroid hormones (e.g., cortisol, aldosterone, testosterone, estrogen) derived from cholesterol
• Amino acid derivatives (e.g., T3, T4, epinephrine, norepinephrine)

Synthesis, Storage, and Secretion of Hormones

• Protein hormones are initially formed as inactive preprohormones, then cleaved to prohormones in the rough endoplasmic reticulum (ER).
• Further processing in the Golgi apparatus produces the active hormone, packaged into secretory vesicles, and stored.
• Specific signals trigger hormone secretion

Synthesis and Storage (Diagram)

• Hormones are synthesized in the cell and packaged in secretory vesicles, then stored.
• Secretion is triggered by a specific stimulus.

Steroid Hormones Storage

• Steroid hormones are stored in smaller quantities.
• Enzymes act on precursor molecules to synthesize hormones.
• Thyroid hormones are stored as part of large protein Thyroglobulin in follicles of the thyroid gland.
• Norepinephrine and epinephrine are stored in granules and secreted via exocytosis.

Feedback Control of Hormone Secretion

• Hormone secretion is generally regulated by internal control mechanisms.
• Negative feedback loops prevent oversecretion or overactivity at the target.

Negative Feedback Mechanism

• Negative feedback controls hormone secretion.
• The endocrine gland and the target cell both have a role in the feedback loop.

Positive Feedback Mechanism

• Positive feedback mechanisms, like the LH surge before ovulation, are also observed.

Cyclical Variations

• Hormone release can fluctuate due to seasonal changes, sleep cycles, or daily rhythms.
• Growth hormone (GH) secretion is higher during the early stages of sleep and decreases as sleep progresses.

Transport of Hormones

• Peptide hormones are often dissolved in plasma.
• Steroid and thyroid hormones circulate bound to plasma proteins.
• This binding makes them inactive, making them more regulated and less likely to diffuse away.

Clearance of Hormones

• Hormone concentration in the blood is determined by secretion rate and metabolic clearance rate (hormone removal rate).

Mechanisms of Action of Hormones

• Hormones generally act via specific receptors.
• Hormone-receptor complex triggers cellular responses.
• Different types of receptors exist (membrane, cytoplasmic, nuclear).
• Receptor number can change through upregulation or downregulation.

Intracellular Signaling

• Hormones often exert their effects by activating receptors, which triggers responses within the cell.
• Membrane receptors, such as ion channel-linked receptors, can change membrane permeability.
• Receptors on cell surface usually trigger signaling pathways to bring cellular responses

G Protein-Linked Hormone Receptors

• Hormone binding to a receptor activates a G protein, initiating a cascade of events.

Enzyme-Linked Hormone Receptors

• Hormone-receptor interactions activate intracellular enzymes, triggering physiological effects.

Activation of Intracellular Enzymes

• Hormone binding activates enzymes.
• AMP activates cellular reactions

By activating gene

• Steroid and thyroid hormones bind intracellular receptors.
• Hormone-receptor complex affects target genes in the nucleus.
• Transcription and protein synthesis are initiated

Cyclic AMP (2nd Messenger)

• Hormones bind to cell surface receptors.
• The receptor activates adenylyl cyclase, leading to cAMP formation.
• cAMP acts as a second messenger.

Calcium-Calmodulin (2nd Messenger System)

• Changes in membrane potential or hormone binding open calcium channels.
• Calcium binds to calmodulin, altering its activity.
• Activated calmodulin activates other enzymes leading to various cellular responses

Phospholipid (2nd Messenger System)

• Hormone activation triggers phospholipase C.
• Phospholipase C cleaves PIP2, releasing IP3 and DAG as second messengers.
• IP3 releases calcium causing cellular responses.
• DAG activates protein kinase C, altering cellular activities

Learning Resources

• Textbook: John E. Hall and Michael E. Hall, Textbook of Medical Physiology, 14th ed. Elsevier, 2021
• ISBN: 978-0-323-59712-8, Chapter 75, Pages 915-927
• Powerpoint presentation in moodle