Introduction to Endocrinology

Bill MontagueMedical & Social Care EducationMSB G18wm5@le.ac.uk

http://www.le.ac.uk/bs/resources/

Plan of Sessions

1. Introduction to Endocrinology

2. Thyroid

3. Adrenal and Anterior Pituitary

4. Tutorial – clinical case studies.

5. Endocrine pancreas and the control of energy metabolism.

Cell communication

Human body composed of functionally specialised cells & tissues.

Normal function depends on these components working together.

Coordination achieved by communication systems:• endocrine• nervous • immune

All communication systems: • use chemical signals (nervous system also uses electrical signals).• work together, not in isolation.

Components of the endocrine system

Endocrine tissue

Biologically active chemical

Transport in blood

Target cells (receptors & response)

Inactivation of chemical

Endocrine glands

Major classes of hormones in man

4 classes identified on structural grounds:

• polypeptide hormones (>20).

• glycoprotein hormones (4).

• amino acid derivatives (3 major hormones).

• steroid hormones (~10).

proteins

Importance of structure

Structure determines:

• how they are made, stored & secreted.

• how they are transported in the blood.

• how they affect their target tissue(s).

• how they are inactivated.

Protein hormones - polypeptides

Largest group.

Most consist of a single chain of amino acids.

Vary in size (number of amino acids):• large = 191 - growth hormone.

• medium = 51 - insulin (two chains – covalently linked).

• small = 3 - thyrotropin releasing hormone.

Protein hormones - glycoproteins

4 hormones:• thyroid stimulating hormone (TSH).• follicle stimulating hormone (FSH).• luteinizing hormone (LH).• human chorionic gonadotropin (hCG).

Consist of 2 polypeptide chains ( & -subunits) with carbohydrate side chains.

Protein hormones (polypeptide & glycoprotein)

Synthesised as larger precursor molecules (prohormone).• converted to smaller biologically active hormone during storage.

Stored in vesicles prior to secretion.

Hydrophilic :• easily transported in blood.• do not readily cross cell membranes - receptors on surface of target

cells.• require intracellular signals (2nd messengers).

Amino acid derivatives

Small molecules synthesised from tyrosine.

HO CH2CH(NH2)COOH

Amino acid derivatives

Adrenaline (catecholamine)

Stored in vesicles in adrenal medulla.

Hydrophilic (weak):• easily transported.

• requires cell surface receptors & intracellular messengers.

HO

HO CH(OH)-CH2-NH(CH3)

Amino acid derivatives

Thyroid hormones• Tri-iodothyronine (T3)• Tetra-iodothyronine (T4) = thyroxine

HO O CH2-CH(NH2)-COOH

I I

I

I

Thyroid hormones

Stored extracellularly in thyroid follicles.

Hydrophobic:• require transport proteins.

• cross cell membranes - intracellular receptors.

Steroid hormones

All synthesised from cholesterol (C27).

Cholesterol stored in steroid producing tissues as cholesterol esters (cholesterol + fatty acid).

Steroid hormones

Steroid hormones vary:• number of C-atoms (27, 21,19 or 18).• number of double bonds. • presence and type of side-groups.

Classes of steroid hormones

C-27• Calciferols - 1,25-dihydroxycholecalciferol (vitamin D)

C-21• Corticosteroids – adrenal cortex

– Gluco-corticoids (cortisol)– Mineralo-corticoids (aldosterone)

• Progestins - progesterone (all steroid producing tissues)

C-19• Androgens - testes, ovary, adrenal cortex (testosterone)

C-18 • Oestrogens – ovary (oestradiol)

Steroid hormones

Not stored:• synthesised on demand from cholesterol esters stored as lipid

droplets.• synthesis involves activation of enzymes in synthetic pathway.

Hydrophobic molecules• require transport proteins.• able to cross cell membranes – receptors are intracellular

(cytoplasmic and/or nuclear).

Control rate of transcription of specific genes.

Steroid hormone synthesis

Cholesterol ester

Cholesterol

Progesterone 7-dehydrocholesterol

Testosterone Aldosterone Cortisol Calciferols

Oestradiol

Components of the endocrine system

Endocrine tissue

Biologically active chemical

Transport in blood

Target cells (receptors & response)

Inactivation of chemical

Hormone concentrations in blood

Hormone concentration normally low (10-10 - 10-8 M) but can increase dramatically depending on:

• rate of secretion.

• extent of binding to carrier proteins.

• rate of inactivation & excretion.

Control of hormone secretion

Rate of secretion usually controlled by negative feedback:

• change in a parameter regulated by the hormone.

• concentration of hormone itself or another hormone.

Control of hormone secretion by change in a parameter regulated by the hormone.

insulin

-cell muscle

[blood glucose]

Control of hormone secretion by change in a parameter regulated by the hormone.

insulin

-cell muscle

[blood glucose]

Control of hormone secretion by change in a parameter regulated by the hormone.

insulin

-cell muscle

[blood glucose]

Control of hormone secretion by concentration of hormone itself or another hormone

Cortisol

ACTH

Adrenal

Anterior Pituitary

Control of hormone secretion by concentration of hormone itself or another hormone

Cortisol

+

ACTH

Adrenal

Anterior Pituitary

Control of hormone secretion by concentration of hormone itself or another hormone

Cortisol

ACTH

Adrenal

Anterior Pituitary

Control of hormone secretion by concentration of hormone itself or another hormone

Cortisol

ACTH

Adrenal

Anterior Pituitary

Hormone transport

Hydrophobic hormones need transport proteins.

Dynamic equilibrium between bound and free forms of hormone:

H(free) + BP H-BP(bound)

Only free form biologically active.

Hormone action

Hormones act by binding to receptors on/in target cells.

Magnitude of response depends on:• concentration of active hormone at target tissue.

• receptor number (can be varied).

• affinity of receptor for hormone.

• degree of signal amplification (enzymes involved).

Mechanism of hormone action

Response

P

R

S

2nd messenger nucleus

S

S DNA

R

R

mRNA

Plasma membrane P

Target tissue responses

Speed of response varies:

• quick (sec-min) - activation of existing enzymes & other functional proteins.

• slow (hr-days) - synthesis of new enzymes & functional proteins.

Hormone inactivation

Steroid hormones & amino acid derivatives:• Small change in structure - increased water solubility.• Products excreted (bile, urine).

Protein hormones:• Large change in structure – degraded to amino acids.• Products reused or broken down.

Tissues involved:• Target tissues.• Liver (products in bile & blood).• Kidney (products in urine).

Hormone functions

Control:• Growth, development & reproduction.• Homeostasis - nutrient & electrolyte.• Response to external stimuli (stress, trauma).

Complex control processes:• many processes controlled by several hormones.• many hormones have several effects.

Failure in these control systems can occur producing clinical problems:

Diabetes, Thyroid disease, Cushing’s & Addison’s diseases

Infertility