ENDOCRINE OVERVIEW

Dr. Amel Eassawi

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OBJECTIVESThe student should be able to: Describe the basic physiologic functions of the endocrine

system and contrast these functions with the basic functions of the nervous systems.

Define hormone, neurohormone, target cell and receptor. Define endocrine, paracrine, autocrine, and intracrine. Describing the chemical nature of hormones. Explain hormone synthesis, storage, and mechanism of

secretion for peptide/ protein, amine and steroid hormones.

Understanding the different mechanisms of hormonal action and the concept of second messenger system.

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INTRODUCATIONAll body systems contribute to maintain homeostasis but the

two major regulatory systems in the body are:1. Nervous system: Coordinates rapid and precise

response and adjusts the body’s interaction to external environment.

2. Endocrine system: Controls activities needing time rather than speed. Regulates, coordinates and integrates cellular functions at a distance to maintains homeostasis.

The nervous system and the endocrine system act together to coordinate functions of all other body systems.

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ENDOCRINE SYSTEMGeneral Principles:• The Endocrine system consist of ductless glands present

throughout the body.• These glands are not connected with each other anatomically, but

functionally make a system.• Their function is carried out by hormones secreted by each gland

into the blood.• Hormones act on distant target cells regulating or directing a

particular function.• Hormones only act on specific target cells due to presence of

receptors.• Binding of hormones with receptors initiate a chain of intracellular

reactions.

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ENDOCRINE SYSTEMDefinitions:Endocrinology is the study of the homeostatic chemical adjustments and other activities accomplished by hormones, which are secreted into the blood by endocrine glands.

Hormones: A long distance chemical messengers that is secreted by an endocrine gland into the blood in response to appropriate signal. The hormone transport to its target cells to exert its effect. Neurohormones: Hormones secreted by neurons. Example: Anti Diuretic Hormone (ADH) and Oxytocin.

Target cell: Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. Receptors: a structure on the surface of a cell or inside a cell that selectively receives and binds a specific substance. A cell is a target because is has a specific receptor for the hormone.

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ENDOCRINE SYSTEM

Functions of the Endocrine System:• Regulates metabolism, and water and electrolyte balance.

• Helps body cope with stressful situations.

• Promotes sequential growth and development. • Controls reproduction.

• Regulates red blood cell production.

• Controls and integrates circulation and digestion and absorption of food.

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Endocrine Glands and Tissues

ENDOCRINE GLANDS AND THEIR HORMONES

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ENDOCRINE GLANDS AND THEIR HORMONES

Releasing hormones/ factors:Secreted by hypothalamus affects the anterior pituitary gland to produce tropic hormones. Tropic hormones are GHRH, TRH,CRH,GNRH, PRH, Somatostatin and Dopamine.

Tropic hormones:Secreted by anterior Pituitary gland to regulate secretion and production of another hormone by other endocrine gland. Tropic hormones are TSH, ACTH, GH, FSH, LH

Example: Thyroid stimulating hormone(TSH) stimulates thyroid gland to secrete thyroid hormones thyroxin(T4) and triiodothyronine(T3)and maintains the structure of thyroid gland. In absence or deficiency of TSH , thyroid gland atrophies and produce low levels of thyroid hormones.

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(d)

Cell-to-Cell Communication

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CELL-TO-CELL COMMUNICATIONNeurotransmitters: Are chemicals secreted by neurons that diffuse across a small gap (synapse) to the target cell. Neurons use electrical signals as well. Paracrine Horomones:Site of synthesis and site of action are close. Hormones act on adjacent cells.Autocrine Horomnes:Site of synthesis and target cell are the same.Intracrine Hormones:Act on the same cell through intracellular receptors. Mostly nuclear receptors.Recurrent / Periodic GlandsAppear and disappear according to physiological demand Example Corpus Luteum and Placenta.

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CLASSIFICATION OF HORMONES

Hormones are classified chemically as:1. Hydrophilic (water soluble) 1. Peptide hormones

2. Amines - Catecholamines - Indoleamines2. Lipophilic (fat soluble) 1. Steroid hormones

2. Amines -Thyroid hormones

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CLASSIFICATION OF HORMONES

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CLASSIFICATION OF HORMONES

1. Peptides hormones:Numerous, having a variable chain of amino acids< 100 amino acids – peptide > 100 amino acids – protein

Examples: Anterior and posterior pituitary gland hormones, Insulin, Glucagon, and Parathyroid hormone.

2. Amines:A. Catecholamine:

Derived from amino acid tyrosine, secreted from adrenal medulla.Example: Epinephrine.

B. Indoleamine: Derived from amino acid tryptophan, produced from pineal gland.Example: Melatonin.C. Thyroid hormone:

Is an iodinated tyrosine derivative, Example: thyroid gland hormones.3. Steroids: Neutral lipids derived from cholesterol, produced by adrenal cortex, testis and ovaries. Example: Cortisol, Aldosterone, Testosterone, and Estrogen.

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HORMONE SYNTHESIS A. Peptide hormones:

Produced and processed by endoplasmic reticulum and golgi complex. Stored in secretary vesicles and release by exocytosis by special signals. Produce physiological response by binding with membrane receptors of target cells. Act primarily by second messenger system altering the activity of preexisting enzymes.

The peptide molecule prepared first is usually a larger precursor called as Preprohormone; It is cleaved to form Prohormone; further cleavage of Prohormone, forms the final mature Hormone. Example: Preproinsulin → Proinsulin → Insulin

This hormone is stored in vesicles of endocrine cells and released on demand

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HORMONE SYNTHESISB. Amines hormones:Catecholamine and Indoleamine are similar to peptide hormones.Thyroid Hormones:Thyroid hormones are produced by thyroid gland by a unique pathway.Hormones are transported in the blood binding to globulin, Albumin andHormones are not usually stored except Thyroxin by combining with

Thyroglobulin.C. Steroid hormones:Synthesized from cholesterol: Once formed, they are immediately released into the circulation; they are not stored. Steroid producing organs produce only specific hormone not all hormones due to specific enzymes needed for the steps. They exert their effect by combining intracellular receptors.

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TRANSPOT AND STORAGE OF HORMONES

Hormones are Transported: in combination with: Globulin Albumin 2 – 3% is in FREE FORM (biologically active)

Storage: Peptides, catecholamine are stored in vesicles. Steroids and thyroid hormones are not stored – except1. Thyroxin combining with Thymoglobulin.2. Insulin: stored in β – cells of pancreas in complex form with Zinc3. ADH – by combining with; - Neurophysin – I - Neurophysin – II

Properties Peptides Catechol-amines

ThyroidHormone

Steroids

Synthesis and storage

Release from parent cell

Transport in blood

Half life

Location of receptor

Response to receptor-ligand

binding

Amines

Polyribosomes -ER as Cytosol/ ATP Ca++ Colloid of follicular cells Mitochondria/ preprohormones/ Chromagranin pendrin (iodide/chloride cytosol

Vesicles Vesicles transporterExocytosis Exocytosis thyroglobulin to megalin endocytosis/ lysosomal diffusion degradation

Most are free Loosely bound to TBG, transthyretin, albumin sex hormone or

albumin albumin corticosteroid BG

Minutes 1-2 minutes T4- 7days, T3- 18 days hours

plasma membrane plasma membrane intracellular intracellular

protein phosphorylation protein phosphorylation genomic genomic genomic genomic

Summary of Chemical Structure, Synthesis, and Transport of Hormones

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COMPLEXITY OF ENDOCRINE FUNCTION

A single endocrine gland produces multiple hormones. Anterior pituitary gland secretes six hormones.

A single hormone may be secreted by more than one gland. Somatostatin is secreted by the hypothalamus and the pancreas.

A single hormone may produce more than one effect. Vasopressin (ADH) affect water reabsorption by acting on V2 receptor and vasoconstriction of arterioles by acting on V1 receptors.

The rate of secretions of some hormones varies over course of time in cyclic pattern. Control of menstrual cycle by sex hormones.

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COMPLEXITY OF ENDOCRINE FUNCTION

A single target cell may be influenced by more than one hormone by activating different enzymes. In liver cells Insulin converts glucose into glycogen and Glucagon converts glycogen into glucose.

The same chemical messenger may be hormone or a neurotransmitter e.g. Norepinephrine.

Some organs have exclusively endocrine function like anterior pituitary gland while, other organs have both endocrine and non endocrine function. Example Testis produces testosterone and sperms.

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MECHANISMS OF HORMONE ACTION

Response depends on both hormone and target cell:

• Lipid-soluble hormones bind to receptors inside the target cells to cause formation of new intracellular proteins, which in turn produce the desired effect.

• Water-soluble hormones bind to receptors on the plasma membrane activating second messenger pathways. This activation alter the activity of preexisting intracellular enzymes to produce the desired effect.

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Target Cells and ReceptorsSignaling after Activation of Receptor by Hormone:1. Ion channel receptors: unlike neurotransmitters, most hormones do not open or close ion channels directly 2. Protein-linked receptors G-proteins3. Enzyme-linked receptors4. Intracellular receptors

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MECHANISMS OF HORMONE ACTION

G Protein–Linked Hormone Receptors.– Many hormones activate receptors that indirectly regulate

the activity of target proteins (e.g., enzymes or ion channels) by coupling with groups of cell membrane proteins called heterotrimeric GTP-binding proteins

(G proteins)

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MECHANISMS OF HORMONE ACTION

Second Messenger Systems Include: Adenylate cyclase which catalyzes the conversion of

ATP to cyclic AMP; Guanylate cyclase which catalyzes the conversion of

GMP to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides);

Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates and diacyl glycerol.

MECHANISMS OF HORMONE ACTION

Adenyl Cyclase• Hormone binds to the

receptor• GDP is released from G

protein• Activate adenyl cyclase

which convert ATP to cAMP• cAMP activates tyrosine

kinase A• Tyrosine kinase A

phosphorylate specific protein for physiological action

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MECHANISMS OF HORMONE ACTION

Phospholipase C• Hormone binds to the

receptor• Phospholipase C liberates

diacylglycerol (DAG) & Inositol trisphosphate (IP3)

• IP3 mobilizes Ca++ from ER• Ca++ and DAG activates

tyrosine kinase C• Tyrosine kinase C

phosphorylate specific protein for physiological action

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MECHANISMS OF HORMONE ACTION

Janus kinase = JAKSignal Transducer and Activator of Transcription = STAT

ENZYME-LINKED HORMONE RECEPTORS

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MECHANISMS OF HORMONE ACTION

Sequence of Steroid hormone action: Endocrine gland secretes steroid hormones. Steroid hormone diffuses through target cell membrane and enters

cytoplasm or nucleus. Hormones combines with a receptor molecule in the cytoplasm or

nucleus. Steroid hormone-receptor complex binds to DNA and promotes

transcription of messenger RNA. Messenger RNA enters the cytoplasm and directs protein synthesis. Newly synthesized proteins produce the steroid hormone’s specific

effects.

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REFERENCES

Human physiology, Lauralee Sherwood, seventh edition.

Text book physiology by Guyton &Hall,11th edition.

Physiology by Berne and Levy, sixth edition.