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Dr. Ammal Esmaeel

Types of glands 1- Exocrine gland

– Contain Ducts

– Have Lumen to store and release the hormones.

2-Endocrine gland

– Ductless

– They released the hormones to Blood stream directly

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Types of glands

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3- Paracrine gland: in this type of glands the secretion of hormones is secreted to the neighbor cells.

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and Hypothalamus

Hypothalamic Hormones

Release Inhibiting Hormones

– Somatostatin

– Prolactin release inhibiting hormone-PIH

Releasing Hormones

– Thyrotropin releasing hormone-TRH

– Growth hormone releasing hormone-GHRH

- Oxytocin hormone and ADH (Vasopressin AVP)

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Hypothalamus

Anterior

Pituitary

Posterior

Pituitary

Hypothalamus and pituitary

1. Posterior Pituitary Hormones

• The Hormons in it manufactured in Hypothalamus, released from Posterior Pituitary.

1-Oxytocin hormons

– Target = smooth muscles. Uterus and Breast (&brain)

– Function = labor and delivery, milk ejection,(pair bonding)

2- ADH (Vasopressin AVP) hormons

– Target = kidneys

– Function = water reabsorption

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2. Anterior Pituitary Hormones HORMONE TARGET FUNCTION

Thyroid (TSH)

Stimulating

Thyroid gland TH synthesis &

release

Growth (GH) Many tissues growth

Adrenocortico-

Tropin (ACTH)

Adrenal cortex Cortisol release

(androgens)

Prolactin (Prl) Breast Milk production

Follicle (FSH) Gonads Egg/sperm prod.

Luteinizing

(LH)

Gonads Sex hormones

Stimulus

Hypothalamus

Releasing Hormone

(Release/Inhibiting Hormone)

Pituitary

Stimulating Hormone

Gland

Hormone Target

Feed back control system

Negative Feedback: Thyroid

Short loop

long loop

Hormones • Hormones: organic biologically active

compounds of different chemical nature that are

produced by the endocrine glands, enter directly

into blood and accomplish the regulation of the

metabolism of compounds and functions on the

organism level.

In summery hormones characterized by:

– Secreted by endocrine gland.

– Specific to target.

– Activate cellular change.

Specific stimulus for hormones secretion

is:

-Nervous impulse

-Concentration of the certain

compound in blood passing through

the endocrine gland.

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Hormones classification

1. Amino acid derivatives: Structurally similar to amino acids

2. Peptide hormones: Chains of amino acids

3. Lipid derivatives: Steroid hormones

Hormones can be:

Freely circulating

– Rapidly removed from bloodstream

Bound to transport proteins

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Amine hormone

• Synthesized from a single amino acid

Examples of amine hormones

Melatonin from tryptophan

Thyroid hormone from tyrosine

Catecholamine from tyrosine

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Thyroid hormones

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thyroxine 1- Synthesis

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Thyroid peroxidase

-Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis - Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I-) actively into the cell. - This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner. - In the colloid, iodide (I-) is oxidized to iodine (I0) by an enzyme called thyroid peroxidase. - Iodine (I0) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues). - In conjugation, adjacent tyrosyl residues are paired together. - The entire complex re-enters the follicular cell by endocytosis. - Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules, which enter the blood by largely unknown mechanisms.

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2-functions of Thyroxine

• Increases cardiac output.

• Increases heart rate.

• Increases ventilation rate.

• Increases basal metabolic rate.

• Potentiates the effects of catecholamines (i.e. increases sympathetic activity).

• Potentiates brain development.

• Thickens endometrium in females.

• increase metabolism of proteins and carbohydrates (i.e. they have a catabolic action)

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Mechanism of action

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Protein/Peptide Hormones

The properties of peptide hormones:

• Hydrophobic.

• Large

• Can't fit through membrane

• It’s mechanism need Second messenger.

Example: Insulin hormones from pancreas

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Pro-insulin insulin

Insulin:

1- The Synthesis Insulin is synthesized in the pancreas within the beta cells (β-cells) of the islets of Langerhans. One to three million islets of Langerhans form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine portion only accounts for 2% of the total mass of the pancreas. Within the islets of Langerhans, beta cells constitute 60–80% of all the cells. In beta cells, insulin is synthesized from the proinsulin precursor molecule by the action of proteolytic enzymes, known as prohormone convertases, as well as the exoprotease carboxypeptidase E. These modifications of proinsulin remove the center portion of the molecule, or C-peptide, from the C- and N- terminal ends of the proinsulin. The remaining polypeptides (51 amino acids in total), the B- and A- chains, are bound together by disulfide bonds. 24

• Insulin is a small protein composed of two amino acid chains connected

by two disulfide linkages.

• Secreted by beta cells, insulin circulates in blood in unbound form.

• It has a plasma half-life of about 6 min and is cleared from circulation

in 10 – 15 min

Connecting peptide (white)

joins the two chains

Proinsulin

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A Chain

B Chain

MOLECULEINSULIN Protein of 21 amino acid A chain and 30 amino acid B chain, Disulfide linkages

Insulin

Insulin:

2- Function :

Stimulate the liver and the muscle cells to take in glucose and store it in the form of glycogen, in anther words stimulates glycogenesis and inhibits glycogenolysis (glycogen catabolism)

Stimulate fat cells to take in blood lipids and turn them into triglycerides.

Has several other anabolic effects throughout the body( Increase amino acid uptake and modification of the activity of numerous enzymes (allosteric effect).

Insulin is used treat diabetes mellitus. Patients with type 1 diabetes mellitus depend on external for their survival because of the absence of the hormone. Patients with type 2 diabetes mellitus have insulin resistance, relatively low insulin production, or both; some type 2 diabetics eventually require insulin when other medications become insufficient in controlling blood glucose levels.

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http://www.diabetes.org/Ref: (animated)

Mechanism of Action of Insulin

•The insulin receptor is a combination of 4 subunits held together by disulfide linkages: two -subunits

lying outside the cell membrane and two -subunits protruding into the cell cytoplasm.

Mechanism of Action of Insulin*

* Adapted from a presentation by Ann K. Snyder, 8/16/2000

Mechanism of Insulin

• When insulin binds to the -subunit in target tissues, the -subunits in turn become activated.

• Activation of the -subunits triggers a series of reactions that draw the glucose transporter to the cell membrane.

• Cells (liver, muscle, adipose, but not brain) are now able to increase their uptake of glucose.

• The cell membrane also becomes more permeable to many amino acids.

Mechanism of Action of Insulin

The mechanism of insulin action

Insulin

Insulin receptor

Glucose

Glycogen

Pyruvate

Fatty acids

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Mechanism of action -3

• Insulin binds to its receptor (1) which in turn starts many protein activation cascades(2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

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Steroid Hormones

The properties of steroid hormones:

• Small

• Hydrophobic/Lipophilic

• Travel in blood with carrier (bounding protein)

• Cytoplasmic or nuclear receptors

• Change protein synthesis

• Example: estradiol, progesterone and testosterone.

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Estradiol

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Estradiol

1- synthesis

Estradiol derived from cholesterol. During the reproductive years, most estradiol in women is produced by the granulosa cells of the ovaries by the aromatization of androstenedione which produced in the theca folliculi cells to estrone, followed by conversion of estrone to estradiol by 17β-hydroxysteroid dehydrogenase. Smaller amounts of estradiol are also produced by the adrenal cortex, and (in men), by the testes.

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androstenedione

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Aromatase

Estrone

Estradiol

17β-hydroxysteroid dehydrogenase

The conversion of testosterone to estradiol

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Aromatase

Testosterone Estradiol

2-Function:

A. Female reproduction: acts as a growth hormone for tissue of

the reproductive organs

B. Sexual development : The development of secondary sex characteristics in women is driven by estrogens

C. Male reproduction: It functions to prevent apoptosis of male sperm cells.

D. Bone: women after menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency

E. Liver: It affects the production of multiple proteins, including lipoproteins, binding proteins, and proteins responsible for blood clotting…..

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Mechanism of action

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Mechanism of action

• Estradiol enters cells freely and interacts with a cytoplasmic target cell receptor. After the estrogen receptor has bound its ligand, estradiol can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell.

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Inactivation of hormones

After biochemical effect hormones are released and metabolized, hormones are inactivated mainly in liver. Inactive metabolites are excreted mainly with urine Half-time life -from several min to 20 min – for the majority of hormones -till 1 h – for steroid hormones -till 1 week – for thyroid hormones