Dr. Noureddini1 In the name of GOD Iran Kashan university of medical sciences Faculty of medicine...

Dr. Noureddini 1

In the name of GOD

IranKashan university of medical sciences

Faculty of medicinedepartment of Physiology and pharmacology

Mahdi noureddiniAssistant professor of physiology

Dr. Mahdi Noureddini 2

Endocrinology andReproduction

Kashan university of medical sciencesFaculty of medicine

department of Physiology and pharmacology Mahdi noureddini

Assistant professor

1. Introduction to Endocrinology2. Pituitary Hormones and Their Control by the Hypothalamus3. Thyroid Metabolic Hormones4. Adrenocortical Hormones5. Insulin, Glucagon, and Diabetes Mellitus6. Parathyroid Hormone, Calcitonin, Calcium and Phosphate

Metabolism, Vitamin D, Bone, and Teeth7. Reproductive and Hormonal Functions of the Male8. Female Physiology Before Pregnancy and the Female

Hormones9. Pregnancy and Lactation10. Fetal and Neonatal Physiology

Introduction to Endocrinology

• Coordination of Body Functions by Chemical Messengers

1. Neurotransmitters2. Endocrine hormones 3. Neuroendocrine hormones 4. Paracrine5. Autocrines 6. Cytokines are peptides secreted by cells into the extracellular fluid and canfunction as autocrines, paracrines, or endocrine hormones. Examples ofcytokines include the interleukins and other lymphokines that are secretedby helper cells and act on other cells of the immune system . Cytokine hormones (e.g., leptin) produced by adipocytes are sometimes called adipokines.

MODES OF HORMONE DELIVERY I:

• AUTOCRINE: – Hormone released feeds-

back on the cell of origin, again without entering blood circulation.

• PARACRINE: – Hormone released diffuses

to its target cells through immediate extracellular space.

– Blood is not directly involved in the delivery.

MODES OF HORMONE DELIVERY II:

• ENDOCRINE: – Most common

(classical) mode, hormones delivered to target cells by blood.

• NEUROENDOCRINE: – Hormone is produced

and released by a neuron, delivered to target cells by blood.

Chemical Structure andSynthesis of Hormones

• 1. Proteins and polypeptides: 2. Steroids : 3. There are no known polysaccharides or nucleic acid hormones.

CHEMISTRY OF HORMONES

• Peptide hormones: largest, most complex, and most common hormones. – Anterior(prolactin,FSH, LH,TSH) and posterior pituitary gland, the pancreas

(insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others(TRH-3,GH-200)

• Steroid hormones: lipid soluble molecules synthesized from cholesterol. adrenocortical steroids (e.g. cortisol and aldosterone). the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).

• Amines: small molecules derived from individual amino acids. – Derivatives of the amino acid tyrosine: thyroid (thyroxine and triiodothyronine)

and the adrenal medullae (catecholamines: epinephrine and norepinephrine).• Eicosanoids: small molecules synthesized from fatty acid substrates (e.g.

arachidonic acid) located within cell membranes

• Made of 1-2 amino acids• Receptors

– Surface– Intracellular

• Small size, OH group• Benzine ring• Examples

– Thyroxin (Tyrosine)– Epinephrine (Tyrosine)– MELATONIN(Tryptophan)

Amine Hormone Structures and Functions

Amine Hormon

e Structures and

Functions

Figure 7-8: Tyrosine-derived amine hormones

Protein and Polypeptide Hormones: Synthesis and Release

Figure 7-3: Peptide hormone synthesis, packaging, and release

Lipid Hormone

• Steroid Hormones

• Eicosanoids

• From cholesterol, lipophilic, enter target cell,

• Cytoplasmic or nuclear receptors (mostly)

• Activate DNA for protein synthesis

• Slower acting, longer half-life

• Examples: cortisol, estrogen & testosterone

Steroid Hormones: Structure and Action

Figure 7-6: Steroid hormones are derived from cholesterol

Eicosanoids

• small molecules synthesized from fatty acid substrates (e.g. arachidonic acid) located within cell membranes

Dr. Mahdi Noureddini 30Figure 18.2

A Structural Classification of Hormones

Hormone Secretion, Transport, and Clearance from the Blood

•Onset of Hormone Secretion After a Stimulus, and Duration of Action of Different Hormones

•Concentrations of Hormones in the Circulating Blood, and Hormonal Secretion Rates

Blood levels of the hormone

• STEROIDS(10-9-10-6m/l)Epinephrine and norepinephrine(10-10m/l)peptide(10-12m/l)

Feedback Control of Hormone Secretion

• Negative Feedback Prevents Overactivity of Hormone Systems.

• Surges of Hormones Can Occur with Positive Feedback.

• Cyclical Variations Occur in Hormone Release.

CONTROL OF HORMONE RELEASE:( feedback )

• The synthesis and secretion of most hormones are usually regulated by negative feedback systems.

• As hormone levels rise, they stimulate target organ responses. These in turn, inhibit further hormone release.

• The stimuli that induce endocrine glands to synthesize and release hormones belong to one of the following major types:– Humoral– Neural– Hormonal

ENDOCRINE SYSTEMENDOCRINE SYSTEM

Blood levels of the hormone

The actual concentration of a circulating hormone in blood at any time reflects:

Its rate of release.

The speed of its inactivation and removal from the body.

Hormones ARE CONSTANTLY BE -SYNTHESIZED- BROKEN DOWN

Clearance of Hormonesfrom the Blood

• Feedback regulation of hormones can occur at all Two factors can increase or decrease the concentration of a hormone in the blood.– the rate of hormone secretion into the blood– The second is the rate of removal of the hormone

from the blood,

• Metabolic clearance rate = Rate of disappearance of hormone from the plasma/Concentration of hormone in each milliliter of plasma

Clearance of Hormonesfrom the Blood

(1) metabolic destruction by the tissues,

(2) binding with the tissues,

(3) excretion by the liver into the bile,

(4) excretion by the kidneys into the urine.

Transport of Hormones in the Blood

• Water-soluble hormones

• Steroid and thyroid hormones,

Mechanisms of Action of Hormones

• Hormone Receptors and Their Activation

• Intracellular Signaling After Hormone Receptor Activation

• Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions

• Hormones That Act Mainly on the Genetic Machinery of the Cell

Hormone Receptors and Their Activation

• 1. In or on the surface of the cell membrane.

– The membrane receptors are specific mostly for the protein, peptide, and catecholamine hormones.

• 2. In the cell cytoplasm.– The primary receptors for the different steroid hormones

are found mainly in the cytoplasm.

• 3. In the cell nucleus.– The receptors for the thyroid hormones are found in the

nucleus and are believed to be located in direct association with one or more of the chromosomes.

The Number and Sensitivity of Hormone Receptors Are Regulated.

(down and up -regulation )

• This down-regulation of the receptors :decreases the target tissue’s responsiveness to the hormone – can occur as a result of

• (1) inactivation of some of the receptor molecules,• (2) inactivation of some of the intracellular protein signaling molecules• (3) temporary sequestration of the receptor to the inside of the cell, away

from the site of action of hormones that interact with cell membrane receptors

• 4) destruction of the receptors by lysosomes after they are internalized,• (5) decreased production of the receptors.

• up-regulation of receptors and intracellular signaling proteins. – When this occurs, the target tissue becomes progressively more

sensitive to the stimulating effects of the hormone.

Intracellular Signaling After Hormone Receptor Activation

• Ion Channel–Linked Receptors.• G Protein–Linked Hormone Receptors.• Enzyme-Linked Hormone Receptors.

– leptin receptor

• Intracellular Hormone Receptors and Activation of Genes.– ( adrenal and gonadal steroid hormones, thyroid

hormones, retinoid hormones,and vitamin D)

• Surface receptor• Hormone binds• Transduction• Enzyme activation• Open channels• Second messenger

systems• Synthesis

Protein &Polypeptide and Amine Hormone Receptors

Figure 7-5: Membrane receptors for peptide hormones

Types of receptors

Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions

• Adenylyl Cyclase–cAMP

• The Cell Membrane Phospholipid

• Calcium-Calmodulin

Signal transduction mechanisms of hormones

Activation of adenylate

cyclase

Inhibition of adenylate

cyclase

Increased phospho-inositide turnover

Tyrosine kinase activation

-adrenergic 2-adrenergic 1-adgrenergic Insulin

LH, FSH, TSH, hCG

Opioid Angiotensin II Growth factors (PDGF, EGF, FGF, IGF-1

Glucagon Muscarinic cholinergic – M2

Muscarinic cholinergic – M3

Growth hormone

Vasopressin- V2 Vasopressin –V1 Prolactin

Hormones That Act Mainly on the Genetic Machinery of the Cell

• Steroid Hormones Increase Protein Synthesis• Thyroid Hormones Increase Gene Transcription in the Cell

Nucleus

Figure 7-7: Steroid hormone action

Measurement of Hormone Concentrations in the Blood

• Radioimmunoassay

• Enzyme-Linked Immunosorbent Assay (ELISA)

Dr. Noureddini1 In the name of GOD Iran Kashan university of medical sciences Faculty of medicine...

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