ENDOCRINE PHYSIOLOGY / Part ONE

2009-2010
drsherwanshal@gmail.com

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Endocrine system maintains homeostasis

The Endocrine System is the major system that maintains stable internal environmet (Homeostasis).

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SENSING AND SIGNALING Endocrine “glands” synthesize and store hormones. These glands have a sensing and signaling system .

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ENDOCRINE VS. NERVOUS SYSTEM
Both are major communication systems in the

body They Integrate stimuli and responses to changes in external and internal environment Both are crucial to coordinated functions of highly differentiated cells, tissues and organs Unlike the nervous system, the endocrine system is anatomically discontinuous.

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NERVOUS SYSTEM

The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.
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Hormones travel via the blood stream to target cells •The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.
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A cell is a target because is has a specific receptor for the hormone
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. A target cell responds to a hormone because it bears receptors for the hormone.

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PRINCIPAL FUNCTIONS OF THE ENDOCRINE SYSTEM
1. Maintenance of the internal environment in

the body (maintaining the optimum biochemical environment). 2. Integration and regulation of growth and development. 3. Control, maintenance and instigation of sexual reproduction, including gametogenesis, coitus, fertilization, fetal growth and development and nourishment of the newborn.

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Types of cell-to-cell signaling

Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream; paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them. Also, intracrine hormones act within the cell that produces them.

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Response vs. distance traveled
Endocrine action: the hormone is distributed in blood and binds to distant target cells. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood. Autocrine action: the hormone acts on the same cell that produced it.

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MAJOR HORMONES AND SYSTEMS
Hypothalamus produces releasing factors that

stimulate production of anterior pituitary hormone which act on peripheral endocrine gland to stimulate release of third hormone Posterior pituitary hormones are synthesized in neuronal cell bodies in the hypothalamus and are released via synapses in posterior pituitary.
Oxytocin and antidiuretic hormone (ADH)

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Types of hormones
Hormones are categorized into four

structural groups, with members of each group having many properties in common: Peptides and proteins Amino acid derivatives Steroids Fatty acid derivatives - Eicosanoids

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Peptide/protein hormones
Range from 3 amino acids to hundreds of

amino acids in size. Often produced as larger molecular weight precursors that are proteolytically cleaved to the active form of the hormone. Peptide/protein hormones are water soluble. Comprise the largest number of hormones– perhaps in thousands

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Amine hormones

There are two groups of hormones derived from the amino acid tyrosine Thyroid hormones and Catecholamines

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Thyroid Hormone
Thyroid hormones are basically a "double" tyrosine

with the critical incorporation of 3 or 4 iodine atoms. Thyroid hormone is produced by the thyroid gland and is lipid soluble Thyroid hormones are produced by modification of a tyrosine residue contained in thyroglobulin, posttranslationally modified to bind iodine, then proteolytically cleaved and released as T4 and T3. T3 and T4 then bind to thyroxin binding globulin for transport in the blood

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Thyroid hormones

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Catecholamine hormones
Catecholamines are both

neurohormones and neurotransmitters.
These include epinephrine, and

norepinephrine  Epinephrine and norepinephrine are produced by the adrenal medulla both are water soluble
Secreted like peptide hormones

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Synthesis of catecholamines

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Amine Hormones
Two other amino acids are used

for synthesis of hormones: Tryptophan is the precursor to serotonin and the pineal hormone melatonin Glutamic acid is converted to histamine

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Steroid hormones
All

steroid hormones are derived from cholesterol and differ only in the ring structure and side chains attached to it. All steroid hormones are lipid soluble
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Types of steroid hormones
Glucocorticoids; cortisol is the major

representative in most mammals Mineralocorticoids; aldosterone being most prominent Androgens such as testosterone Estrogens, including estradiol and estrone Progestogens (also known a progestins) such as progesterone

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Steroid hormones
Are not packaged, but synthesized and

immediately released Are all derived from the same parent compound: Cholesterol Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER Steroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells
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Steroid hormones
Steroid hormones are not water soluble so have

to be carried in the blood complexed to specific binding globulins. Corticosteroid binding globulin carries cortisol Sex steroid binding globulin carries testosterone and estradiol In some cases a steroid is secreted by one cell and is converted to the active steroid by the target cell: an example is androgen which secreted by the gonad and converted into estrogen in the brain

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Steroid hormone synthesis All steroid hormones are derived from cholesterol. A series of enzymatic steps in the mitochondria and ER of steroidogenic tissues convert cholesterol into all of the other steroid hormones and intermediates. The rate-limiting step in this process is the transport of free cholesterol from the cytoplasm into mitochondria. This step is carried out by the Steroidogenic Acute Regulatory Protein (StAR)
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Steroid hormone synthesis

•The cholesterol precursor comes from cholesterol synthesized within the cell from acetate, from cholesterol ester stores in intracellular lipid droplets or from uptake of cholesterol-containing low density lipoproteins.

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1,25-Dihydroxy Vitamin D3

1,25-dihydroxy Vitamin D3 is

also derived from cholesterol and is lipid soluble Not really a “vitamin” as it can be synthesized de novo Acts as a true hormone
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Fatty Acid Derivatives Eicosanoids
Arachadonic

acid is the most abundant precursor for these hormones. Stores of arachadonic acid are present in membrane lipids and released through the action of various lipases. These hormones are rapidly inactivated by being metabolized, and are typically active for only a few seconds.
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 Eicosanoids are a large

group of molecules derived from polyunsaturated fatty acids. The principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thromboxanes.

Fatty Acid Derivatives Eicosanoids

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Regulation of hormone secretion
Sensing and signaling: a biological need is

sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are:
1. 2. 3. 4. 5.

Receipt of stimulus. Synthesis and secretion of hormone. Delivery of hormone to target cell. Evoking target cell response. Degradation of hormone.

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Mechanism Of Hormone Action

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Receptor Location

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Control of Endocrine Activity •The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid. •Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial.
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Control of Endocrine Activity The concentration of hormone as seen by target cells is determined by three factors: •Rate of production •Rate of delivery •Rate of degradation and elimination
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Control of Endocrine Activity Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits.

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Control of Endocrine Activity
Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells - high blood flow delivers more hormone than low blood flow.

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Control of Endocrine Activity
Rate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. Shutting off secretion of a hormone that has a very short half-life causes circulating hormone concentration to plummet, but if a hormone's biological half-life is long, effective concentrations persist for some time after secretion ceases.
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Feedback Control of Hormone Production
Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion
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Inputs to endocrine cells

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Neural control
 Neural input

to hypothalam us stimulates synthesis and secretion of releasing factors which stimulate pituitary hormone production and release

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Feedback control
Negative feedback is most common:

for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation
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Negative feedback effects of cortisol

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Substrate-hormone control
Glucose and insulin: as glucose

increases it stimulates the pancreas to secrete insulin

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Feedback control of insulin by glucose concentrations

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