introduction to the endocrine system ziying wang institute of pharmacology school of medicine,...

Introduction to the endocrine system

Ziying WANGInstitute of Pharmacology School of Medicine, Shandong Universitywangziying@sdu.edu.cn

Part 1 Introduction

Endocrinology

1. Definition: the study of hormones and their functions.

2. History: (1) Ancient China

(2) 1849, Berthold

(3) 1855, Addison’s disease

(4) Ernest Starling

1902, Hormone,

1905, “Endocrine system” Ernest Starling(1866-1927)

Endocrine vs. exocrine

Characteristic of endocrine gland

• Without duct

• The endocrine cells arranged in cluster, follicle or cords

• Rich in capillaries

• The secretion is hormone which transported by blood circulation

Endocrine system

1. Endocrine glands(1) Classical endocrine glands

(2) Extensive endocrine glands

2. Endocrine cells

Classical endocrine glands

Hormones

Definition -- chemical messengers

-- secreted by endocrine gland or cells

-- released into the blood

-- effect on target cells through receptors

Major Hormones

Hormones

Functions• to control the regulatory systems in the body

(1) homeostasis

(2) metabolism

(3) growth and development

(4) reproduction

Endocrine vs. Nervous regulationEndocrine vs. Nervous regulation

Neural regulation-exerts point-to-point

-control through nerves

-electrical in nature and fast

Endocrine regulation-broadcasts its hormonal messages to essentially all cells -by secretion into blood and extracellular fluid-requires a receiver to get the message

-slow and wider

Neuroendocrine regulation: 1928, Scharrer

Transportation of Hormones

Endocrine (Telecrine, hemocrine)

Paracrine

Transportation of Hormones

Types of hormones

1. Peptide hormones

2. Steroids

3. Amine hormones (derivatives of the amino acid tyrosine)

Synthesis of hormones

Synthesis of steroid hormones

Synthesis of amine hormones

Synthesis of peptide hormones

The comparison of hormones

Receptors Carrier

protein

Orally active

storage

Peptides Cell membrane

No Not usually Hormone

Steroids Cytoplasm/nucleus

Yes Yes, mostly Precursor

Thyroid hormone

nucleus Yes Yes Precursor

Catecholamines Cell membrane

No No Hormone

The transport of hormones

1. Peptide and CA: water-soluble2. Steroids and thyroid hormone: bound to proteinsEg. Thyroid hormones binding globulin (THBG)

Cortisol binding globulin (CBG)

Sex hormones binding globulin (SHBG)

Effects of hormone binding proteins:(1) Increase the solubility

(2) Create an accessible reserve

(3) Increase the biological half time

The metabolism of hormones

1. Peptide hormones: degradation in a lysosome

2. Steroids: excreted in an unchanged form

3. Catecholamines: COMT and MAO

4. Thyroxine: removing the iodine residues

Results of metabolism(1) Inactivation

(2) Activation

Properties of the hormone effect

1. Specificity

2. Signal transmission

3. High biological efficiency

Properties of the hormone effect

1.Specificity: target, receptor

Properties of the hormone effect

2. Signal transmission

Properties of the hormone effect

3. High Biological Efficiency

Low plasma concentration

(nmol – pmol/L)

→great regulatory function

Part 2 Important concepts in endocrine regulation

Patterns of hormone secretion

Different hormones have markedly different patterns of secretion.

1. Set point regulation

2. Episodic secretion

3. Diurnal variation

Regulation of hormone secretion:endocrine axis

Endocrine axis

1. Long-loop feedback: (1) Classical negative feedback (2) Regulated by the end product

2. Short-loop feedback Regulated by the intermediate product

3. Ultrashort-loop feedback

Regulation of hormone secretion: negative feedback

Regulation of hormones secretion

• 1. Synergistic effects

• 2. Permissive effect

• 3. Antagonist effects

Interaction Between the Hormones

• 1. Synergistic effects

(1) Additive: same effect of the hormones on one target organ

(2) Complementary: work on different stages of a physiological procedure

Interaction Between the Hormones

• 2. Permissive effect• A hormone enhances the responsiveness

of a target organ to the second hormone, and increases the activity of the second hormone.

Interaction Between the Hormones

3. Antagonist effects• One hormone antagonize the effects of anoth

er.• Eg. The regulation effect of glucagon and insulin on

blood glucose metabolism

Interaction Between the Hormones

Part 3 Endocrine disorders

Endocrine disorders

• Normal amount of hormones are essential for the body.

• Either excessive or insufficient hormones secretion are disorders.

• Excessive secretion: hyper-

• Insufficient secretion: hypo-

Endocrine disorders

Secondary: Hypothalamus or pituitary disorder

Primary: endocrine glands disorder

Endocrine disorders

Part 4 Endocrine investigations

General principles

1. Purposes: diagnosis/monitoring2. After clinical pattern recognition or

understanding of physiology and anatomy3. Blood test maybe basic or dynamic.1) Basic test : 9:00h, fasted2) Dynamic test: (1) stimulation test :when suspect a hormone is too low. (2) suppression test: when suspect a hormone is too high.

Measurement of hormones

1. Biological sample (1) Blood (2) Urine (3) Biopsy

2. Image: radiological imaging is vital.

Ectopic hormone secretion

1. Definition: The inappropriate secretion of hormones by tissues that do not usually produce that hormones.

2. Clinical significance: as a feature of endocrine tumors.

3. Diagnosis: combined methods.

Receptors and hormone actionThe first step of a hormone’s action is to bind to specific receptors at the target cell.

Protein in nature

(may contain carbohydrate or phospholipid moieties)

Classification by location:

1.Cell surface receptors

2. Intracellular receptors:

(1) cytoplasm receptors

(2) nucleus receptors

Receptors of hormones

Classification by mechanisms:

Receptors of hormones

1.Second messenger mechanisms:

Peptide hormones and CA

--bind the receptors on the membrane --activate some enzyme on the membrane-- regulate the concentration of second

messengers in the cytoplasm

Mechanism of hormones action

G-protein-coupled Receptor

Second messenger mechanisms

2. Gene expression mechanism:

Intracellular receptors(1) --bind the receptors in the cytoplasm -- HR complex goes into nuclearOr -- bind the receptors in the nuclear (2) -- bind to target DNA(3) – regulate transcription

Mechanism of hormones action

Gene expression mechanism

Gene expression mechanism

cytoplasm receptors nucleus receptors

3. Receptors activate a protein kinase

For insulin or growth hormone receptors

Mechanism of hormones action