Lecture 9 part 1

Intro to Endocrine

Introduction
The nervous and endocrine systems coordinate all of the body systems
The nervous system does so through the action of neurons, and the neurotransmitters they secrete
Neurotransmitters regulate activity at synapses

The endocrine system uses hormones produced by endocrine structures that are released into the interstitial fluid where they may enter the blood stream and travel to distant sites in order to produce their effects Both neurotransmitters and hormones exert their effects by binding to specific receptors on target cells.
Several mediators can act as both neurotransmitters and hormones

Hormones and their Receptors

Hormone
A mediator molecule that regulates the activity of cells in the local environment, or in a distant part of the body

Hormone Receptor
A protein structure that a mediator molecule binds to
Can be on the cell surface or inside the cell Receptor is specific for a specific mediator molecule

Changes in the receptor due to binding of a hormone or neurotransmitter cause changes in the cell A target cell is a cell that has the receptor for a specific neurotransmitter or hormone

Types of Hormones
Main types of hormones
Autocrine Paracrine Endocrine

Types of Hormones
Autocrine hormones
local hormones that are secreted, and bind to the same cell that secreted them causing a change in that cell. Autocrine signals allow the cell to sense and respond to a change in that cells environment

Types of Hormones
Paracrine hormones
local hormones that are secreted into interstitial fluid and act on nearby cells

Types of Hormones
Endocrine hormones
secreted into interstitial fluid and then typically absorbed into the bloodstream to be carried systemically to any cell that displays the appropriate type of receptor

Solubility of Hormones
Hormones can be divided into two broad chemical classes.
This chemical classification is useful because the two classes exert their effects differently

Lipid soluble hormones

bind to receptors in the cytoplasm or nucleus of the cell
Receptors inside the cell

Water soluble hormones

bind to receptors on the surface of the cell
Receptor is typically a G-protein

Solubility of Hormones
Lipid soluble hormones
consist of steroid hormones, thyroid hormones, and the gas nitric oxide Steroid hormones are derived from cholesterol Thyroid hormones (T3 and T4) are synthesized by attaching iodine to the amino acid tyrosine The gas nitric oxide (NO) is both a hormone and a neurotransmitter. Its synthesis is catalyzed by the enzyme nitric oxide synthase

Solubility of Hormones
Lipid soluble hormones require a carrier protein for transport in the watery environment of the blood

Once they arrive at their destination, however, they are able to freely pass through the plasma membrane to bind to receptors located in the cytoplasm or the nucleus of the target cell When a lipid soluble hormone enters a cell and binds with intracellular receptors (in the cytoplasm or the nucleus), the activated receptorhormone complex alters gene expression: It turns specific genes of the nuclear DNA on or off.

Free hormone

Blood capillary

Lipid-Soluble Hormone Action

1 Lipid-soluble

Transport protein

hormone diffuses into cell

2 Activated

receptor-hormone complex alters gene expression

Nucleus Receptor

DNA Cytosol
3 Newly formed

mRNA

mRNA directs synthesis of specific proteins on ribosomes

Ribosome
New protein
4 New proteins alter

cell's activity

Target cell

Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones.

Slide 6

Extracellular fluid

Steroid hormone

Plasma membrane

Cytoplasm Receptor protein

1 The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor.

Receptorhormone complex 2 The receptorhormone complex enters the nucleus.

3 The receptor- hormone complex binds a specific DNA region. Binding initiates transcription of the gene to mRNA. 4

Nucleus

Receptor Binding region

DNA

mRNA

5 The mRNA directs protein synthesis. New protein

2013 Pearson Education, Inc.

Solubility of Hormones
Water soluble hormones
include peptide, protein, and amine hormones as well as a group of local hormones derived from the arachidonic acid on our cell membranes called eicosanoids Peptide hormones (3 to 49 amino acids long) and protein hormones (50 to 200 amino acids long) are amino acid polymers
Ex peptide: ADH and oxytocin Ex protein: growth hormone and insulin

Amine hormones are derived from the modification of certain amino acids
Ex: catecholamines (epi and norepi) and histamine

The two major types of eicosanoids are prostaglandins and leukotrienes both play a role in mediating the inflammatory response

Solubility of Hormones
Water soluble hormones are easy to transport in the watery blood. The plasma membrane of target cells, however, is impermeable to them
Water soluble hormones exert their effects by binding to receptors exposed to the interstitial fluid on the surface of target cells
The hormone binds to its receptor protein and causes a change in that protein which activates a signal cascade the hormone binding to its receptor acts as the first messenger in a cascade of signal transduction

Solubility of Hormones
The first messenger (the hormone) then causes production of a second messenger inside the cell, where specific hormonestimulated responses take place
One common second messenger is cyclic AMP (cAMP). Neuro-transmitters, neuropeptides, and several sensory transduction mechanisms (vision) also act via second-messenger systems

Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones.

Slide 6

Recall from Chapter 3 that G protein signaling mechanisms are like a molecular relay race. 1 Hormone (1st messenger) binds receptor. Hormone Receptor G protein Enzyme 2nd (1st messenger) messenger

Adenylate cyclase

Extracellular fluid

G protein (Gs)

Receptor

GTP GTP ATP GDP GTP

cAMP

5 cAMP activates protein kinases.

Inactive protein kinase

Active protein kinase

Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc.) Cytoplasm 2 Receptor activates G protein (Gs). 3 G protein activates adenylate cyclase. 4 Adenylate cyclase converts ATP to cAMP (2nd messenger).

2013 Pearson Education, Inc.

Blood capillary

Water-Soluble Hormone Action

1 Binding of hormone (first messenger)

to its receptor activates G protein, which activates adenylate cyclase

Water-soluble hormone Receptor

Adenylate cyclase
Second messenger cAMP

G protein ATP

2 Activated adenylate
cyclase converts ATP to cAMP

Protein kinases

6 Phosphodiesterase
inactivates cAMP Activated protein kinases

3 cAMP serves as a

second messenger to activate protein kinases Protein ATP

4 Activated protein
kinases phosphorylate cellular proteins

ADP Protein P

5 Millions of phosphorylated
proteins cause reactions that produce physiological responses

Target cell

Effects of Hormones
Prostaglandins (PGs) and leukotrienes are eicosanoid hormones with local control.
They are synthesized from membrane lipids and have widespread effects PGs mediate pain, platelet aggregation, fever, and inflammation. They regulate smooth muscle contraction, gastric acid secretion, and airway size
aspirin is a drug that works by inhibiting an enzyme necessary for synthesis of certain PGs: the ones that facilitate pain and the inflammatory response

Effects of Hormones
Endocrine hormones control a variety of physiological processes. Among other things, they:
Balance the composition and volume of body fluids Regulate metabolism and energy production Direct the rate and timing of growth and development Exert emergency control during physical and mental stress (trauma, starvation, hemorrhage) Oversee reproductive mechanisms

EFFECTS OF HORMONES
(Interactions Animation)
o

Introduction to endocrine hormones: Regulation, secretion and concentration

You must be connected to the internet to run this animation

Endocrine System Glands

Glands that secrete endocrine hormones into the bloodstream are called endocrine glands
They are one of two major types of glands in the body, the other being exocrine glands (which secrete their products into ducts)

We will focus on endocrine

Hormone Interactions
Target cell responsiveness to a hormone depends on three factors
Blood levels of hormone Relative number of receptors on or in target cell Influences exerted by other hormones and molecules

Hormone Interactions
Blood levels of hormone
Increase in blood levels of hormone increase the likelihood of hormone binding to receptor and causing effect

Relative number of receptors on or in target cell

Generally, a target cell has 2,000 to 100,000 receptors for a particular hormone
These receptors are constantly being produced and destroyed by the cell

Hormones can influence the number of their receptors on a target cell

Up-regulationtarget cells form more receptors in response to low hormone levels Down-regulationtarget cells lose receptors in response to high hormone levels

More receptors = more sensitive cell to hormone

Hormone Interactions
Influences exerted by other hormones and molecules
Lowered or increased binding affinity can result from multiple causes such as pH changes, the presence or absence of specific hormones or cofactors, and even effects of second messenger cascades.
A lowered affinity for binding may limit the effect of a hormone on its target cell

The actions of some hormones on target cells require a simultaneous or recent exposure to a second hormone
In this case, the second hormone is said to have a permissive effect

When 2 or more hormones act together to produce an effect greater than either of them produce alone, the effect is said to be synergistic When one hormone opposes the actions of another, the two hormones are said to have antagonistic effects

Control of Hormones
Release of most hormones occurs in short bursts with little or no secretion between bursts When stimulated, an endocrine gland will release its hormone in more frequent bursts, increasing the concentration of the hormone in the blood In the absence of stimulation, bursts will decrease in frequency causing blood levels of the hormone to decrease Regulation prevents hormone levels being too high (overproduction) or too low (underproduction)

Control of Hormones
Hormone secretion is regulated by;
signals from the nervous system (neural stimuli) chemical changes in the blood (humoral stimuli) other hormones (hormonal stimuli)

Humoral Stimuli
Changing blood levels of ions and nutrients directly stimulate secretion of hormones Example: Ca2+ in blood
Declining blood Ca2+ concentration stimulates parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca2+ concentrations to rise and stimulus is removed

Neural and Hormonal Stimuli

Nerve fibers stimulate hormone release
Ex: Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines

Hormones stimulate other endocrine organs to release their hormones

Hypothalamic hormones stimulate release of most anterior pituitary hormones Anterior pituitary hormones stimulate targets to secrete still more hormones Hypothalamic-pituitary-target endocrine organ feedback loop:
hormones from final target organs inhibit release of anterior pituitary hormones

Control of Hormones
Most hormonal regulatory systems work via negative feedback, but a few operate via positive feedback
In a negative feedback system the hormone output reverses a particular stimulus. For example:

Blood Ca2+ level is controlled by the parathyroid hormone (PTH). If blood Ca2+ is low, there is a stimulus for the parathyroid glands to release more PTH. PTH then exerts its effects in the body until the Ca2+ level returns to normal. If the level gets too high the body will cease PTH production and secrete calcitonin lower the Ca2+ levels.

Control of Hormones
This example shows how PTH and calcitonin have negative feedback influence on one another

Control of Hormones
In a positive feedback system the hormone output reinforces and encourages the stimulus. For example, during childbirth, the hormone oxytocin stimulates contractions of the uterus, and uterine contractions in turn stimulate more oxytocin release, a positive feedback effect

CONTROL OF HORMONES
(Interactions Animation)
o

Hormones Summary

You must be connected to the internet to run this animation