Metabolism module Introduction to Hormones Kufa Medical School

Communication is the key Multi-cellular organisms stay together because cells communicate – When they come into contact (autocrine) Cell surface chemicals – When they are close (paracrine) Local diffusion of chemical messengers – When they are far apart (endocrine) Chemical messengers in the blood stream (Hormones) Electrical transmission (Nerves)

Extracellular signal molecules can act over either short or long distance

Chemical communication A chemical messenger must be produced by one cell And detected by another – Target cell – Receptors Receptors are (insulin as example) – Specific for particular messengers – Linked to metabolic processes in the cell Directly or indirectly Receptors always involved even when transmission is mostly electrical (see Figure again)

Receptors always involved even when transmission is mostly electrical

So: Local and long distance Cells in contact – Direct interaction Immune system Cells nearby – Local diffusion of messengers Paracrine Distant cells – Chemicals in the blood stream Endocrine via hormones – Rapid electrical transmission nerves

Hormones and Nerves What is the meaning of Hormone? Is it differ from nerve?

Hormone Chemical signal produced by endocrine glands that travel in the bloodstream to affect other tissues

Hormones Nerves released from endocrine glands – Travel in blood stream – reach all parts of the body in about 30 seconds to – Only interact where there are receptors – But can have different effects in different places – Good for coordinated multiple responses Rapid communication from point to point – Electrical signal – One end of body to the other in milliseconds – Normally initiated by chemical signal or change – Act in only one place – By locally diffusing chemical messenger released from nerve end Neuro-transmitter – Good for rapid, precise control

Hormones Can always ask the same questions – Where does it come from? – What is its chemical nature? – How is it made? – What causes its release? – How is it transported in the blood stream? – What is and where is the receptor on the target cell? – How does its binding interact with the metabolism of the target cell? – What effects does it have? – How is it inactivated?

Q) How many endocrine glands are there in the body,

Where? - Endocrine glands Head & neck – Pineal body (Melatonin) – Hypothalamus (Releasing H & release inhibitory) – Pituitary gland – anterior and posterior parts – Thyroid glands – Parathyroid glands (4 in No.)

Where? - Endocrine glands Abdomen – Adrenal glands – cortex and medulla – Pancreas – Kidneys – Gut

Where? - Endocrine glands Pelvis – Gonads Ovaries Testes – Placenta (pregnancy)

Q: what classes do they fall in?

What? – classes of hormones Polypeptide hormones – Around 20 Glycoprotein hormones – Four Amino acid derivatives – 3 major Steroid hormones – Around 10

Structure of hormones Structure determines – How they are made – How they are transported in the blood – Nature and location of receptors on cells – How they are inactivated

Polypeptide hormones Largest group Nearly all single chain peptides vary in chain length – Growth hormone amino acids – Insulin - 51 amino acids in two chains – TRH – 3 amino acids

Glycoprotein hormones All have two polypeptide chains with carbohydrate side chains –  and  chains (  is similar while  is vary) Related families – Thyroid stimulating hormone (TSH) – Follicle stimulating hormone (FSH) – Luteinising hormone (LH) – Human chorionic gonadotrophin (HCG)

Polypeptide and glycoprotein hormones Synthesised as larger precursor molecules – Pro-hormones Stored in vesicles before release Cleaved to active hormone Example : perproinsulin→proinsulin →insulin

Amino acid derivatives All from tyrosine Thyroid hormones – Tetra-iodothyronine (T4) – Tri-iodothyronine (T3) Catecholamines (Ex: Adrenaline & noradrenaline) CH 2 CH(NH 2 )COOH HO

Adrenaline Stored in vesicles in adrenal medulla Hydrophilic molecule Does not easily cross cell membranes O HO CH(OH)-CH 2 -NH(CH 3 )

Thyroid hormones Stored extra- cellularly in follicles in thyroid gland As colloid Hydrophobic Readily cross cell membranes (has cytoplasmic and nuclear receptors) OCH 2 -CH(NH 2 )-COOHHO I I I I (T4)

Steroid hormones Derived from cholesterol

Steroids Classed by: – Number of carbon atoms C27, C21,C19 or C18 – Number of double bonds – Different side chains

Classes of steroid hormones C27 – Calciferols – e.g. vitamin D C21 – Corticosteroids – adrenal cortex Glucocorticoids (cortisol) Mineralocorticoids (eg aldosterone) – Progestins – eg progesterone from ovaries C19 – Androgens – eg testosterone from testes C18 – Oestrogens – eg oestradiol from ovaries

Steroids Not stored by cells Synthesised on demand from cholesterol esters Hydrophobic Readily cross cell membranes

Steroid synthesis Cholesterol ester progesterone7-dehydrocholesterol testosteronealdosteronecortisolcalciferols oestradiol

Travelling in the blood Few hormones soluble enough to travel in simple solution – Peptides – Adrenaline Most should bind to (usually) proteins – Often specific Steroids Thyroid hormones

The endocrine cells are stimulated chemically to release hormones Produces negative feedback control Tends to keep hormone concentration in blood at controlled level

Negative feedback Just Example is HPT axis TRH secretion stimulated when blood thyroxine levels fall TRH acts on anterior pituitary to stimulate TSH secretion TSH acts on thyroid gland to make thyroxine levels rise High thyroxine reduces TSH secretion again Overall acts to keep blood thyroxine levels constant Many hormones controlled in similar ways

Critical role of anterior pituitary Many hormones controlled by other hormones (‘trophic’ hormones) Secreted by anterior pituitary gland Allows brain to influence the endocrine system

Hormone action Always bind to receptors If hormone can cross membrane (eg steroids) receptors located inside cells Receptor hormone complex can move Binding linked directly to metabolic changes – Often expression of genes

Hormone action If hormone cannot cross membrane Binds to receptor on cell surface Activates second messenger pathway Second messenger (inside the cell) exerts metabolic effects – Often modifying action of enzymes

Hormone action

Inactivation Steroids and amino-acid derivatives – Small changes in structure – Recycled or excreted Peptides – Degraded to amino acids Inactivation may occur in target tissues, but also in other tissues, especially the liver

So, for any endocrine system Where does the hormone come from? What is its chemical nature? How is it made? What causes its release? How is it transported in the blood stream? What is and where is the receptor on the target cell? How does its binding interact with the metabolism of the target cell? What effects does it have? How is it inactivated?