Concepts in Endocrinology

Concepts in Endocrinology

• Define hormone, target cell, and receptor
• Contrast endocrine, paracrine, autocrine, and neuroendocrine based on site of release and pathway to target tissue
• Contrast peptide, steroid, and amine hormones in terms of receptor location, signal transduction, solubility in blood, and transport in blood

Homeostatic Control

• Homeostatic control mechanisms include reflex loops where the response decision is made at a distance from the target cell
• Two general classes: endocrine and neuroendocrine
• Endocrine: hormone reaches its site of action via blood circulation
• Neuroendocrine: hormone is secreted from neurons into the blood to act at a distance

Receptors Determine Specificity

• Hormones are widely distributed throughout the body and have access to all cells but only target cells respond
• Target cells possess a receptor for the hormone
• Receptor contains a recognition site that binds its hormone with high affinity and selectivity
• Lipid solubility of the hormone dictates the cellular location of its receptor
• Plasma insoluble hormones bind to intracellular receptors; plasma soluble hormones bind to cell surface receptors

Hormone Signaling

• Peptide hormones bind to cell surface receptors, which activate a second messenger
• Second messengers provide amplification, memory, and complex regulation
• Permissiveness (or tropism) occurs when the actions of a tropic hormone sensitize the target tissue to a second hormone

Inactivation of Hormone Signaling

• Inactivation of hormone signaling occurs at two levels: cellular inactivation and systemic inactivation
• Cellular inactivation involves the termination of the receptor's response
• Systemic inactivation involves homeostatic control mechanisms such as negative feedback

Negative Feedback Loops

• Negative feedback loops eliminate the initiating stimulus
• Example: pituitary and adrenal glands are in a negative feedback loop
• The stimulus, hypoglycemia, leads to the secretion of cortisol from the adrenal gland
• Cortisol acts on liver, muscle, and fat to raise blood glucose levels

Importance of Hormone Levels

• Disorders of the endocrine system result from too little or too much hormone or target cell resistance
• Hypo-secretion: results in an insufficiency of hormone
• Hyper-secretion: results in an excess of hormone
• Resistance: is an abnormal target organ response due to receptor and/or second messenger dysfunction

Hormone Measurement

• Hormones are present at very low concentrations (nM) in body fluids and many have related structures
• Measurement requires very high sensitivity and high specificity
• Two common types of assays: radio-immune assay (RIA) and bioassay (suppression and stimulation)
• RIA measures total hormone (carrier-bound hormone plus free) but only free is active
• Bioassay measures biological activity to a challenge dose of hormone or substrate

General Concepts

• Peptide hormones are soluble in plasma, act via surface receptors, are fast-acting, and short-lived
• Thyroid hormones and steroid hormones are insoluble in plasma, act via intracellular receptors, are slow-acting, and long-lived
• Thyroid and steroid hormones can be converted to more active (or less active) hormones within target tissues