Organisms need to be able to respond to their external environment.
This is more complicated in multicellular organisms because often intercellular communication is necessary.
As the organism gets bigger and more complex so does the system that controls response to the external environment.
All organisms need to be able to respond to their external environment.
The 2 common control systems in vertebrate animals are
1. The nervous system
2. The endocrine system

The nervous sytem is often the immediate response system and controls responses in the short term.
The endocrine system is slower acting and controls long term response.
Glands
Glands are groups of secretory cells.
There are 2 types of glands
exocrine and endocrine.

Chemical Messengers
Hormones are the chemicals produced by endocrine glands that are secreted into blood and distributed around the body
There are some other specialized cell secretions namely autocrine and paracrine.
Autocrine secretions are substances that effect the the secreting cell itself (negative feedback). Example norepinephrine from neurons.
Paracrine secretions are substances that effect neighboring cells. Example histamine release from mast cells cause local inflammation.
Pheromones are another type of chemical messenger but they work between organisms.

Endocrine system
Endocrine glands secrete hormones that are taken up in the blood and distributed around the body of the animal.
Are all cells effected by any one hormone?
No.
Why?
Hormones only effect cells with hormone receptors.

So how do hormones effect target cells?
The binding of a hormone to its receptor causes a biochemical change in the cell.
Hormones can be put into 4 categories
1. amines (e.g.epinephrine, T₄)
2. peptides (insulin, growth hormone)
3. glycoproteins (FSH, LH)
4. steroids (estrogen, testosterone)
These chemical groups have 2 classes of action depending on their ability to cross cell membranes.

Lipid Soluble Hormones
Steroids and thyroxine are lipid soluble and can move through cell membranes.
These hormones are insoluble in water and cannot dissolve in blood plasma.
They are carried in the blood attached to carrier proteins.
At target cells they must dissociate from the carrier protein before passing through a cell membrane.

Steroid Hormones
Steroids move into the cytoplasm and bind to a cytoplasmic receptor (or nuclear receptor).
Hormone/cytoplasmic receptor complex moves into nucleus.
2 hormone/receptors (homodimer) bind to DNA binding sites and initiates transcription of a gene or genes.

Thyroxine
Thyroxine T₄, moves through the cell membrane. Inside the cell it is converted to T₃.
T₃ moves into the nucleus where it binds to a receptor.
T₃ hormone/receptor complex forms a dimer with 9-cis-retinoic acid they bind to DNA and facilitate transcription of a gene.

Binding of a hormone (ligand) to a receptor is a complex interaction. Receptors differ in their affinity (likelihood of binding) to hormones. The affinity can be altered by physical conditions such as pH. Binding may also be effected by competitive binding by other molecules. Many drugs are designed to competitively exclude hormones binding to receptors i.e. antogonists or agonists (e.g. antihistamines).

Lipid Insoluble Hormones
Peptide, glycoprotein and most amine hormones bind to receptors in the cell membrane.
Reception leads to the activation of a second messenger or messengers that activate other cell proteins (enzymes).

Many receptors have similar mechanisms in the cell by using the same second messengers.
Three important second messengers are
Cyclic AMP (cAMP)
Inositol triphosphate (IP₃)
Calcium ions (Ca²⁺)

Lets look at the mechanism using Cyclic AMP (cAMP)as the second messenger. Sometimes called the adenylate cyclase-cyclic AMP second messenger system
1. Hormone binds to receptor on membrane surface.
2. G-protein in membrane activated (GTP plus protein).

Lets look at the mechanism using Cyclic AMP (cAMP)as the second messenger. Sometimes called the adenylate cyclase-cyclic AMP second messenger system
1. Hormone binds to receptor on membrane surface.
2. G-protein in membrane activated (GTP plus protein).

3. G-protein activates adenylate cyclase on inner surface of cell membrane.
4. Adenylate cyclase converts ATP to cAMP in cytoplasm.
5. cAMP binds to a protein kinase, causing activation of its subunit that activates effector protein.

Effect in a cell depends upon the effector protein, which can be different in different cells.
G-protein, adenylate cyclase and protein kinase are all enzymes. A kinase is an enzyme that transfers phosphate groups to other organic molecules.

There is an amplification process.
One G-protein molecule can activate many molecules of adenylate cyclase.
One molecule of adenylate cyclase form many molecules of cAMP.
One molecule of protein kinase A can activate many effector proteins.

Example - Glycogen breakdown
Epinephrine (muscle) or glucagon (liver) bind to receptors.
G-protein activated and in turn activates adenylate cyclase.
Adenate cyclase converts ATP to cAMP.
cAMP activates protein kinase A.
Protein kinase A phosphorylates (activates) phosphorylase kinase.

Phosphorylase kinase activates (phosphorylates) phosphorylase b to form phosphorylase a.
Phosphorylase a cleaves glucose from glycogen.

Note : there is a similar mechanism for inhibiting the cAMP second messenger system.
Another receptor when bound to an inhibitory hormone activates a G-protein that inactivates adenylate cyclase.

cAMP is inactivated in a cell by another enzyme phosphodiesterase. So the initial stimulation of the cell is short lived.
The continued effect on the cell therefore depends on the level of secretion of the initial hormone.
Caffeine (and drug theophylline) inhibit the action of phosphodiesterase.

Hormones and responses that use cAMP as a second messenger
Epinephrine (b receptors)
skeletal muscle - breakdown glycogen
heart - increase rate and force
smooth muscle - relax
Thyroid Stimulating Hormone
Glucagon
Serotonin
Vasopressin

Inositol triphosphate (IP₃) and calcium are second messengers and sometimes third messengers in similar cascades of enzyme activation that greatly magnify the molecules involved after hormone reception and produce specific and often multiple cell responses.

When epinephrine binds to an a receptor:
phospholipase c in cell membrane activated (via g-protein)
Phospholipid (phosphatidylinositol, PIP₂) in membrane to produce inositol phosphate, IP₃ and diacylglycerol, DAG.
IP₃ binds to receptors on the endoplasmic reticulum and Ca²⁺ is released into cytoplasm.
Ca²⁺ binds to a cytoplasmic protein calmodulin.Ca/calmodulin activates protein kinases.
Depending on the protein kinases present, cAMP pathways and Ca/calmodulin pathways can have the same or different effect in a cell.

Calcium can be introduced to the cytoplasm in different ways.
e.g. receptor gated channelsvoltage gated channels in neurons

Hormones can have more than one receptor
Epinephrine is the best example with 5, a₁, a₂, b₁, b₂, and b₃.
b₁,b₂, and b₃ use cAMP as a second messenger.
a₂ is coupled to an inhibitory G-protein that decreases cAMP levels.
a₁,uses inositol triphosphate (IP₃) as the second messenger.

Therefore hormones can have different effects on different cells depending upon the receptors that the cell produces.
Regulation of hormone effects in any one cell can be through the increase or decrease of receptors.

Glands to be covered in this section
adrenal glands
thyroid and parathyroid
pancreas
pineal
hypothalamus and pituitary

Adrenal gland
The adrenal gland is developmentally and functionally two separate glands, namely the adrenal cortex and the adrenal medula.

Adrenal medulla
Produces catecholamines, mainly epinephine (adrenaline) and norepinephrine which stimulates "fight or flight response".
Alters vasoconstriction cardiac output, bronchodilation etc.
Secreted in response to sympathetic nervous stimulation.

Adrenal cortex
Produces 3 groups of corticosteroids,
Mineralocorticoids (e.g. aldosterone) which regulate Na⁺ reabsorption and K⁺ secretion in the kidneys.
Glucocorticoids ( e.g. cortisol) which have widespread metabolic effects including increasing glucose and amino acids availability in cells. Secretion increases during stress and in large doses is anti-inflamatory and suppresses the immune response.
Sex hormones , weak androgens. They are relatively insignificant in males because of the larger quantities ptoduced by the testes. In females the androgens are thought to be important in stimulating the sex drive.
Stimulated hormonally by ACTH.

Thyroid gland
Follicular cells produce thyroxine T₄ which effects metabolic rate, thermogenesis and development of most cells.
Thyroxine, T₄ is a compound made from the amino acid tyrosine and 4 iodine ions. Another form of thyroid hormone is T₃.

Specialized parafollicular cells of the thyroid produce calcitonin which stimulates osteoblasts to build bone tissue and reduce Ca²⁺ in blood.
Parathyroid gland produces parathyroid hormone that stimulates osteoclasts to break down bone and increase blood Ca²⁺.

Pancreas
The pancreas functions as an exocrine gland and an endocrine gland. Exocrine function is secretion of digestive enzymes. Endocrine function from Islets of Langerhans, cells located amongst exocrine glands

Alpha cells
Produce glucagon which stimulates breakdown of glucose in liver.
Beta cells
Produce insulin which stimulates the uptake of glucose by cells.

Pineal Gland
A small but interisting gland which is part of the brain. Gland size reduces after age 7.
Controlled by suprachiasmatic nucleus (SCN) part of the hypothalamus which is stimulated by dark.
The SCN is the primary controller of circadian rhythms.
Pineal gland secretes melatonin. Secretion increases at night and decreases during daylight hours

Function of melatonin has not been well studied but...
Melatonin depresses gonad development in seasonal breeding animals.
High levels in young children, decreases at puberty in humans.
Melatonin induces sleep and enhances the immune response.


Pituitary gland
Developmentally and functionally two separate glands, the posterior pituitary (neurohypophysis) and the anterior pituitary (adenohypophysis).
Located under the brain, close to the hypothalamus and joined to it by the infundibulum.

Posterior pituitary
Hormones actually produced in the cell bodies of neurons in the paraventricular nucleus and the supraoptic nucleus of the hypothalmus.
They are transported down axons and released in the posterior pituitary.
Hormones secreted are oxytocin, which effects milk let down and uterine contraction in mammals and antidiuretic hormone (ADH), which increases water resorption in kidneys.

Anterior pituitary
Produces 6 hormones that control hormone release in other organs and development
1. growth hormone (somatotropin), all cells
2. thyroid stimulating hormone (TSH), thyroid
3. adrenocorticotropin, adrenal cortex)
4. follicle stimulating hormone (FSH), gonads
5. luteinizing hormone (LH), gonads
6. prolactin (mammary gland development).

Hormones from the anterior pituitary are in turn regulated by hormone releasing or hormone inhibiting hormones produced by neurons in the hypothalmus. (see table 11.7)
e.g. gonadotropin releasing hormone (GnRH)
growth hormone releasing hormone (GHRH)
growth hormone inhibiting hormone (GHIH) (somatostatin)
prolactin inhibiting hormone (PIH)
thyrotropin releasing hormone (TRH)
corticotropin releasing hormone (CRH)

Many hormones are controlled by negative feedback systems, maintaining homeostasis.
So levels fluctuate around a set point.
What sets the point?

The hypothalamus provides the integration point between our nervous system and our endocrine system.
Can your thoughts effect your health?

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This webpage was created by Peter King. Please contact the the author with comments at pking@fmarion.edu.
Last edited July 20, 2010.
http://people.fmarion.edu/pking/humanphys/endocrine.html
copyright Peter King.