DR.MOUAADH ABDELKARIM ASSISTANT PROFESSOR OF PHYSIOLOGY COLLEGE OF MEDICINE DEPARTMENT OF PHYSIOLOGY TEL: Endocrinology College of Dentistry

Endocrine System: Overview Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus

Endocrine glands:  Pituitary  Thyroid  Parathyroid  Adrenal  Pancreas  Ovaries  Testes Introduction

Roles of the Endocrine System HOMEOSTASIS: maintenance of the internal environment METABOLIC REGULATION: storage and use of energy substrates. RESPONSES TO EXTERNAL STIMULI. CONTROL OF GROWTH, REPRODUCTION AND DEVELOPMENT.

Introduction Definition :  Hormone is a chemical substance released by a group of cells to control the function of other type of cells. Types of hormones :  Affect many different types of cells (eg. GH and Thyroxine)  Affect only specific target cells (eg. ACTH and estrogen)

Endocrine Glands and Hormones The hypothalamus has both neural functions and releases hormones Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart Hormones can exert their effects at distance from their site of production.

Hormones - Hormones: – Affect metabolism of target organs. Help regulate total body metabolism, growth, and reproduction. – Neurohormone: Specialized neurons that secrete chemicals into the blood rather than synaptic cleft. Chemical secreted is called neurohormone.

Introduction The multiple hormone systems play a key role in regulating almost all body functions:  Metabolism  Growth and development  Water and electrolyte balance  Reproduction  Behavior Released into and carried via bloodstream to target tissues

Introduction What are target cells? Target cells refer to cells that contain specific receptors (binding sites) for a particular hormone.

Three general classes of hormones: Three general classes of hormones exist: 1. Proteins and polypeptides, including hormones secreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others. 2. Steroids secreted by the adrenal cortex (cortisol and aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone). 3. Derivatives of the amino acid tyrosine, secreted by the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine). There are no known polysaccharides or nucleic acid hormones.

Peptide (Protein) Hormones Synthesis as preprohormone  post- translational modification to prohormone  then hormone They can dissolve in water (plasma)

-Prohormones: An intraglandular precursor of a hormone, e.g., proinsulin. - Preprohormone: is the precursor protein to one or more prohormones

Steroid Hormones Secreted by gonads, adrenals cortex, placenta Derived from cholesterol  Cross membranes (no storage) Usually Bound to Carrier proteins

Amine Hormones Derived from amino acid tyrosine They include the thyroid hormones, epinephrine and norepinephrine (produced by the adrenal medulla), and dopamine (produced by the hypothalamus).

Mechanism of action of hormones Mechanism of action : 1. Hormone-receptor interaction (first messenger) 2. Enzyme activation 3. Release of the second messenger 4. Effects on cellular function

Receptors:  Hormonal receptors are large proteins  ,000 receptors/cell  Receptors are highly specific for a single hormone Receptor’s Location:  On the surface of cell membrane (peptides and catecholamines)  In the cell cytoplasm (Steroids)  In the cell nucleus (thyroid hormones) Receptors of hormones

Mechanism of Hormone Action G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to the insideproteinscell

G protein ( Adynylate cyclase- c AMP )

G protein (Phospholipase C -IP 3 )

Amino Acid-Based Hormone Action: PIP-Calcium Hormone binds to the receptor and activates G protein G protein binds and activates a phospholipase enzyme Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP 3 (both act as second messengers) DAG activates protein kinases; IP 3 triggers release of Ca 2+ stores Ca 2+ (third messenger) alters cellular responses

(Tyrosine Kinase System) Is used by insulin & many growth factors to cause cellular effects Surface receptor is tyrosine kinase  Consists of 2 units that form active dimer when insulin binds

Mechanism of action ( steroid hormones )

Steroid hormones and thyroid hormone diffuse easily into their target cells Once inside, they bind and activate a specific intracellular receptor The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein This interaction prompts DNA transcription to produce mRNA The mRNA is translated into proteins, which bring about a cellular effect

Clearance of hormones Two factors control the concentration of a hormone in the blood:  The rate of its secretion  The rate of its removal (metabolic clearance) Hormones are cleared by:  Metabolic destruction by tissues  Excretion by the liver into bile  Excretion by the kidney into urine Clearance of protein-bound hormones is slower than clearance of peptide hormones

Blood levels of hormones are controlled by feedback mechanisms : - Negative feedback - Positive feedback Control of Hormone Release

Feedback Mechanisms Negative feedback loop – original stimulus reversed – most feedback systems in the body are negative – used for conditions that need frequent adjustment Positive feedback loop – original stimulus intensified – seen during normal childbirth

Hormones and cellular changes Hormones produce one or more of the following cellular changes in target cells  Alter plasma membrane permeability  Stimulate protein synthesis  Activate or deactivate enzyme systems  Induce secretory activity  Stimulate mitosis

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