Overview of Biochemical Endocrinology

Hormone- "chemical substance secreted by a ductless gland into blood that is transported to a distant target organ whose activity it specifically affects".

Target Tissues- have receptors or specific binding proteins for each hormone

Properties of Hormones:

1. They are biosynthesized.

2. They operate at vanishingly small concentrations in blood (10-12 to 10-8 M, nano-pico).

3. They have short half lives.

4. They often exert multipoint control and operate at a number of target organs; hormones awaken existing potential in target cells that are preprogrammed to respond.

5. They are feedback regulated by: (a) themselves, (b) the product(s) of their action, (c) the central nervous system.

Chemistry

There are several chemically distinct classes of hormones: amine(epinephrine), peptide (insulin, glucagon) and steroid (cortisol).

 

Insulin, Glucagon, Epinephrine and Cortisol are the Hormones that Control Glucose Homeostasis:

Hormone Receptors:

Interaction between hormone and receptor forms the "hormone receptor complex".

Strength of binding is expressed as the dissociation constant Kd, the concentration at which the binding sites are half-saturated.

Classification of Hormones by Receptor Properties:

Group I: Hormones that bind to intracellular receptors: Glucocorticoids, mineralocorticoids, estrogens, progestins, androgens, vitamin D, thyroid, retinoic acid

Group II: Hormones that bind to cell surface receptors:

Group IIA: The second messenger is cAMP: vasopressin, glucagon, b-adrenergic catecholamines, somatostatin, opioids.

Group IIB: The second messengers are IP3 (inositol trisphosphate) / Ca2+ and diacylglycerol (DAG): oxytocin, angiotensin II, a-adrenergic catecholamines.

Group IIC: The cell surface receptor posses tyrosine protein kinase activity (intracellular messenger unknown): insulin, growth factors.

Group IIC': The cell surface receptor recruits soluble tyrosine kinases: growth hormone.

Group IID: The second messenger is cGMP: atrial natiuretic peptide (ANP).

 

General Features of Hormone Classes, Group I and Group II:

Feature Group I Group II
Solubility Lipophilic Hydrophilic
Plasma T1/2 Long (Hours to Days) Short (Minutes)
Receptor Location Intracellular Plasma Membrane
Signal Mediator Receptor-Hormone Comp. cAMP,cGMP,Ca2+,IP3,DAG

 

Steroid / Thyroid / Retinoic Acid Hormone Actions:

Group I- lipophilic, derived from cholesterol (except thyroid and retinoic acid)

Passively diffuse through the plasma membrane of the target cell to associate with their receptors.

The hormone-receptor complex is assumed to be the intracellular messenger

Effects of these hormones are quite specific.

Cell Surface Acting Hormone Action:

Group II: peptide and amine hormones bind to membrane spanning receptors (7 transmembrane); communicate through second messengers, cAMP (Group IIA) or Ca2+ / IP3 / DAG (Group IIB).

G-Proteins

Review

E = The Effector Protein, Adenylate Cyclase

R = Receptor, 7-transmembrane cell surface receptor

 

Note: once the Effector protein is active the second messenger c-AMP is produced activating Protein Kinase A and starting a "cascade" of events leading to transmission of message and physiological / biochemical responses.

Hormones Functioning via IP3 / Ca2+ and DAG:

PIP2 = Phosphatidylinositol-4,5-bisphosphate

IP3 = Inositol-1,4,5-triphosphate

DAG = Diacylglycerol

PLC = Phospholipase C

PKC = Protein Kinase C

CaM Kinase = Calmodulin Kinase

 

[1] hormones bind to receptor

[2] receptor is coupled to phospholipase C by Gp

[3] Phospholipase C splits PIP2 into IP3 and DAG

[4] and [5] IP3 mobilizes intracellular (stored) Ca2+ from the ER for activation of CAM

[6] and [7] DAG activates protein kinase C which is further activated by Ca2+

[8]the concerted action of these two kinases elicit cellular responses

Clinical Correlate

Bacterial Toxins:

Cholera Toxin

Symptoms: watery stools, vomiting, cyanotic, low blood pressure, rapid / weak pulse

Treatment: IV solution of elctrolytes, tetracycline

Cause: cholera toxin inhibits GTPase preventing breakdown of GTP to GDP and locking the a subunit in the activated state producing a continuous oversupply of cAMP

Pertussis Toxin

Freezes Gi leaving Gs continuallt active, producing an oversupply of cAMP

 

© Dr. Noel Sturm 2011