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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
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Dr. Mahdi Noureddini 2
Endocrinology andReproduction
Kashan university of medical sciencesFaculty of medicine
department of Physiology and pharmacology Mahdi noureddini
Assistant professor
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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
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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.
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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.
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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.
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Chemical Structure andSynthesis of Hormones
• 1. Proteins and polypeptides: 2. Steroids : 3. There are no known polysaccharides or nucleic acid hormones.
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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
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• 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
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Amine Hormon
e Structures and
Functions
Figure 7-8: Tyrosine-derived amine hormones
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Protein and Polypeptide Hormones: Synthesis and Release
Figure 7-3: Peptide hormone synthesis, packaging, and release
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Lipid Hormone
• Steroid Hormones
• Eicosanoids
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• 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
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Steroid Hormones: Structure and Action
Figure 7-6: Steroid hormones are derived from cholesterol
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Eicosanoids
• small molecules synthesized from fatty acid substrates (e.g. arachidonic acid) located within cell membranes
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Dr. Mahdi Noureddini 30Figure 18.2
A Structural Classification of Hormones
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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
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Blood levels of the hormone
• STEROIDS(10-9-10-6m/l)Epinephrine and norepinephrine(10-10m/l)peptide(10-12m/l)
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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.
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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
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ENDOCRINE SYSTEMENDOCRINE SYSTEM
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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
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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
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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.
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Transport of Hormones in the Blood
• Water-soluble hormones
• Steroid and thyroid hormones,
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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
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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.
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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.
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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)
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• 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
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Types of receptors
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Second Messenger Mechanisms for Mediating Intracellular Hormonal Functions
• Adenylyl Cyclase–cAMP
• The Cell Membrane Phospholipid
• Calcium-Calmodulin
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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
ACTH
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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
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Steroid Hormones: Structure and Action
Figure 7-7: Steroid hormone action
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Measurement of Hormone Concentrations in the Blood
• Radioimmunoassay
• Enzyme-Linked Immunosorbent Assay (ELISA)
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