Lecture # 15: The Endocrine System 2 The Endocrine System (Chapter 17)

Objectives

1- To identify the chemical classes to which various hormones belong.2- To describe how hormones stimulates their target cells.

Hormone ChemistryMost hormones fall into three chemical classes:

2- Peptides and Glycoproteins: They are chains of 3 to 200 or more aminoacids. 3- Monoamines (biogenic amines): They are made from aminoacids and retain an amino group.

Estrogens, progesterone, testosterone, cortisol, corticosterone, aldosterone, DHEA, and calcitriol are steroid hormones.

1- Steroids: They are derived from cholesterol.

1- Steroids:

They are secreted by gonads and adrenal glands.

Steroid hormones are derived from cholesterol.

2- Peptides and GlycoproteinsThey are created from chains of amino acids. They are secreted by pituitary and hypothalamus.Oxytocin, antidiuretic hormone, releasing and inhibiting hormones, and anterior pituitary hormones.

3- Monoamines (biogenic amines)They are derived from amino acids and secreted by adrenal, pineal, and thyroid glands.

Epinephrine, norepinephrine, melatonin, and thyroid hormone are mono-amines.

Aminoacid

Hormone Receptors and Mode of ActionHormones stimulate only those cells that have receptors for them.

Receptors are protein or glycoprotein molecules on plasma membrane, in the cytoplasm, or in the nucleus.

Usually each target cell has a few thousand receptors for a given hormone.

Receptors act like switches turning on metabolic pathways when hormone binds to them.

Metabolic effects can be achieved by different mechanisms:

1- Activation of genes in the nucleus to initiate the transcription and synthesis of some proteins.

2- Activation of specific enzymes that are inactive in the cytosol.

3- Changes in the membrane permeability and membrane potentials.

2- Activation of specific enzymes that are inactive in the cytosol.

Protein kinases are proteins present in the cytosol as inactive proteins.When protein kinases are activated they have the ability to activate many other enzymes.

1- Activation of genes in the nucleus to initiate the transcription and synthesis of some proteins.

3- Changes in the membrane permeability and membrane potentials.

Free hormones (hydrophilic)

Bound hormones (hydrophobic)

Transportprotein

Second-messengeractivation

Blood

Targetcell

Receptor innucleus

Receptor in plasmamembrane

Tissue fluid

Hydrophobic Hormones (Steroids and Thyroid hormones)

1- They penetrate plasma membrane and enter nucleus.

2- They act directly on the genes changing target cell physiology.3- It takes several hours to days to show effect due to lag for protein synthesis.

Hydrophilic Hormones (Peptides and

Catecholamines)1- They cannot penetrate into target cell.

2- They must stimulate target cell physiology indirectly.

Hormone Receptors and Mode of Action

ThyroxineBinding Globulin

1- Thyroid hormone enters target cell by diffusion – mostly as T4 with little metabolic effect.

2- Within target cell, T4 is converted to more potent T3.

3- T3 enters target cells and binds to receptors in chromatin and acti-vates genes.4- Activated genes make a muscle protein (myosin) enhancing cardiac muscle response to sympathetic stimulation and strengthening heartbeat.5- Activated genes also make the enzyme Na+ - K+ ATPase. One of its effects is to generate heat, thus accounting for the calorigenic effect of thyroid hormone.

The Action of Thyroid Hormone on a Target CellAction of Hydrophobic Hormones

Action of Hydrophilic HormonesThe hormone binds to a cell-surface receptor, which is linked to a second messenger system on other side of the membrane.Second messengers:1- cAMP produced by the enzyme adenylate cyclase.2- Diacylglycerol (DAG) and Inositol triphosphate (IP3) produced by the enzyme phospholipase.

The enzymes adenylate cyclase and phospholipase are integral proteins of the plasma membrane of target cells.

Cyclic AMP as a Second Messenger

Hormone

Receptor

G protein (inactive)

Adenyl cyclase

(inactive)

Adenyl cyclase

(activated) ATP

cAMP

Opens ion channels

Activates enzymes

Receptor

Hormone

G protein

Adenylate cyclase

cAMP

They are the first messengers that bind to receptors and leading to the appearance of a second messenger.

They are glycoproteins of the plasma membrane that bind specific hormones and determine the cell’s hormonal sensitivity.

Receptor

It is an enzyme complex coupled to the plasma membrane, which is activated by the receptor-enzyme complex. Once it is activated, it activates the adenyl cyclase.

It is an enzyme that converts the ATP in cyclic AMP (cAMP)

It is the second messenger that activates the enzymes protein kinases.

They are enzymes that perform phosphorylations that activates or inactivates other enzymes

Protein kinase

(Inactive)

Protein kinase

G proteins and Hormone Activity

Hormone

Cyclic AMP as a Second Messenger

Hormone–receptor binding activates a G protein.

1

G protein activates adenylate cyclase.2

Adenylate cyclase produces cAMP.3

cAMP activates protein kinases.4

Protein kinases phosphorylate enzymes. This activates some enzymes and deactivates others.

5

6 Activated enzymes catalyze metabolic reactions with a wide range of possible effects on the cell.

Metabolic reactions:SynthesisSecretionChange membrane potentials

Diacylglycerol (DAG) and Inositol Triphosphate (IP3) as Second Messengers

1 A hormone binds to its receptor, which activates a G protein.

The G protein migrates to a phospholipase molecule and activates it.

2

The phospholipase transforms a phospholipid molecule into DAG.

3

DAG activates a protein kinase, an enzymes that phosphorylates other enzymes with various metabolic effects.

4

1 A hormone binds to its receptor, which activates a G protein.

The G protein migrates to a phospholipase molecule and activates it.2

The phospholipase transforms a phospholipid molecule into IP3.

3

The IP3 raises calcium concentration in the cytosol in 2 ways:

Ca2+

8 Calcium may bind to other gated membrane channels and alter the membrane potential of the cells.

9 Calcium may activate cytoplasmic enzymes that alter cell metabolism.

1- IP3 opens gated channels in the plasma membrane.

6

2- IP3 opens gated channels in the endo-plasmic reticulum.

7

Calcium is a Third Messenger that can have three effects:

10 Calcium may bind to the protein Cadmodulin, which activates a protein kinase.