Mechanisms of Intercellular Communication (Table 18-1)
Direct communication
Transmission: Through gap junctions
Chemical Mediators: Ions, small solutes, lipid-soluble materials
Distribution of Effects: Usually limited to adjacent cells of the same type that are interconnected by connexons
Paracrine communication
Transmission: Through extracellular fluid
Chemical Mediators: Paracrine factors
Distribution of Effects: Primarily limited to a local area, where paracrine factor concentrations are relatively high
Endocrine communication
Transmission: Through the bloodstream
Chemical Mediators: Hormones
Distribution of Effects: Target cells are primarily in other tissues and organs and must have appropriate receptors
Synaptic communication
Transmission: Across synapses
Chemical Mediators: Neurotransmitters
Distribution of Effects: Limited to a very specific area; target cells must have appropriate receptors
Hormone Categories
Groups based on chemical structure:
Amino acid derivatives
Thyroid hormones
Catecholamines
Melatonin
Peptide hormones
Synthesized as prohormones
Lipid derivatives
Eicosanoids
Leukotrienes
Prostaglandins
Steroid hormones
Hormones - Lipid Derivatives
Eicosanoids
Derived from arachidonic acid, a 20-carbon fatty acid.
Paracrine factors that coordinate cellular activities and affect enzymatic processes (such as blood clotting) in extracellular fluids.
Some eicosanoids (such as leukotrienes) have secondary roles as hormones.
A second group of eicosanoids – prostaglandins – involved primarily in coordinating local cellular activities.
In some tissues, prostaglandins are converted to thromboxanes and prostacyclins, which also have strong paracrine effects.
Steroid hormones
Derived from cholesterol
Released by:
The reproductive organs (androgens by the testes in males, estrogens and progestins by the ovaries in females)
The cortex of the adrenal glands (corticosteroids)
The kidneys (calcitriol)
Because circulating steroid hormones are bound to specific transport proteins in the plasma:
They remain in circulation longer than secreted peptide hormones
Hormone Examples by Chemical Structure
Amino Acid Derivatives
Catecholamines
Example: Epinephrine
Tryptophan Derivatives
Example: Melatonin
Peptide Hormones
Lipid Derivatives
Eicosanoids
Example: Prostaglandin E
Steroid Hormones
Example: Estrogen
Thyroid Hormones
Thyroxine (T4)
Mechanisms of Hormone Action
Hormone Receptor
Is a protein molecule to which a particular molecule binds strongly
Each cell has receptors for several different hormones
Cells of different tissues have different combinations of receptors
Presence or absence of specific receptor determines hormonal sensitivity
Down-regulation
Presence of a hormone triggers decrease in number of hormone receptors
When levels of particular hormone are high, cells become less sensitive to it
Type II Diabetes
Up-regulation
Absence of a hormone triggers increase in number of hormone receptors
When levels of particular hormone are low, cells become more sensitive to it
Type I diabetes
Secretion and Distribution of Hormones
Hormones circulate freely or travel bound to special carrier proteins
Free Hormones
Remain functional for less than 1 hour
Diffuse out of bloodstream and bind to receptors on target cells
Are broken down and absorbed by cells of liver or kidneys
Are broken down by enzymes in plasma or interstitial fluids
Thyroid and Steroid Hormones
Remain in circulation much longer because most are “bound”
Enter bloodstream
More than 99 percent become attached to special transport proteins
Bloodstream contains substantial reserve of bound hormones
Hormone Binding
Two possible receptor locations on target cells:
Receptor on plasma membrane
Requires use of First and Second Messengers
Receptor in cytoplasm or nucleus
Steroid hormones
Thyroid hormones
Hormones and Plasma Membrane Receptors
Catecholamines and Peptide Hormones
Are not lipid soluble
Unable to penetrate plasma membrane
Bind to receptor proteins at outer surface of plasma membrane (extracellular receptors)
Require second messenger inside the cell, while the first messenger (the hormone) stays outside the cell
Hormones and Intracellular Receptors
Alter rate of DNA transcription in nucleus
Change patterns of protein synthesis
Directly affect metabolic activity and structure of target cell
Include steroids and thyroid hormones
Eicosanoids (note these are paracrines – therefore they act locally)
Are lipid soluble
Diffuse across plasma membrane to reach receptor proteins on inner surface of plasma membrane (intracellular receptors)
Effects of Intracellular Hormone Binding
Action of steroid hormones
Steroid hormone diffusion through membrane lipids
Binding of hormone to cytoplasmic or nuclear receptors
Binding of hormone–receptor complex to DNA
Gene activation
Transcription and mRNA production
Translation and protein synthesis leading to alteration of cellular structure or activity
Action of thyroid hormones
Thyroid hormone Transport across plasma membrane
Binding of hormone to cytoplasmic or nuclear receptors
Binding of hormone–receptor complex to DNA
Gene activation
Transcription and mRNA production
Translation and protein synthesis & Binding of receptors at mitochondria and nucleus, leading to alteration of cellular structure or activity & Increased ATP production
First Messenger
Leads to second messenger
May act as enzyme activator, inhibitor, or cofactor
Results in change in rates of metabolic reactions
Important Second Messengers
Cyclic-AMP (cAMP)
Derivative of ATP
Cyclic-GMP (cGMP)
Derivative of GTP
Calcium ions
The Process of Amplification
Is the binding of a small number of hormone molecules to membrane receptors
Leads to thousands of second messengers in cell
Magnifies effect of hormone on target cell
G Protein
Enzyme complex coupled to membrane receptor
Involved in link between first messenger and second messenger
G Proteins and cAMP
Adenylate cyclase is activated when hormone binds to receptor at membrane surface and changes concentration of second messenger cyclic-AMP (cAMP) within cell
Increased cAMP level accelerates metabolic activity within cell
G Proteins and Calcium Ions
Activated G proteins trigger:
Opening of calcium ion channels in membrane
Release of calcium ions from intracellular stores
G protein activates enzyme phospholipase C (PLC)
Enzyme triggers receptor cascade
Production of diacylglycerol (DAG) and inositol triphosphate (IP3) from membrane phospholipids
May further activate more calcium ion channels through protein kinase C (PKC)
Calcium ions may activate calmodulin, which causes further cellular changes
The Hypothalamus
Provides highest level of endocrine function by integrating nervous and endocrine systems
Three mechanisms of integration:
Hypothalamic neurons synthesize two hormones that are transported to and released by the posterior pituitary
Antidiuretic hormone (ADH)
Synthesized by the supraoptic nuclei
Oxytocin (OXT)
Synthesized by the paraventricular nuclei
Secretes regulatory hormones that control anterior pituitary gland endocrine cells
Contains autonomic centers that directly stimulate the endocrine cells in the adrenal medullae
Stimulated in response to sympathetic division activation
In response, adrenal medulla releases epinephrine and norepinephrine into bloodstream
Hypophyseal portal system
Capillary networks and interconnecting vessels between the hypothalamus and the pituitary gland (hypophysis, pituitary gland)
Regulatory hormones released from the hypothalamus at the median eminence of infundibulum
Move from interstitial fluid into fenestrated capillaries
Carried to anterior pituitary in portal vessels (portal veins)
Form second capillary network within the anterior pituitary
Allows hypothalamic hormones to reach target cells in anterior pituitary directly, without mixing and diluting in general circulation
Two classes of regulatory hormones
Releasing hormones (RH)
Stimulate hormone synthesis and secretion
Inhibiting hormones (IH)
Prevent hormone synthesis and secretion
Pituitary Gland
Pituitary gland or hypophysis
Small, oval gland
Lies within sella turcica of sphenoid bone
Releases nine peptide hormones
Seven from anterior lobe (adenohypophysis)
Called tropic hormones because they “turn on” other endocrine glands
Two from posterior pituitary (neurohypophysis)
All nine bind to membrane receptors and use cAMP as 2nd messenger
Exhaustion of lipid reserves and the breakdown of structural proteins as the body’s primary energy source, damaging vital organs
Infections that develop due to suppression of inflammation and of the immune response, a secondary effect of the glucocorticoids that are essential to the metabolic activities of the resistance phase
Cardiovascular damage and complications that are related to the ADH and aldosterone-related elevations in blood pressure and blood volume
Inability of the adrenal cortex to continue producing glucocorticoids, which results in a failure to maintain acceptable blood glucose concentrations
Failure to maintain adequate fluid and electrolyte balance