Physiology I
Section 6
Basic Endocrine Concepts

Key Words:

Hormone: A powerful chemical messenger that exists in very low concentrations and is carried by the blood or transported via the ECF to a target organ.

Another View:  
Chemical substance that is secreted into the internal body fluids by one cell or a group of cells and has a physiological control effect on other cells of the body.

Another View:   
A hormone is a chemical messenger secreted by a cell or group of cells into the internal body fluids and has a physiological control effect on other cells of the body.

Endocrine: A classic type of hormone secreted by a cell and carried in the blood stream thus travels a distance. Ie. Thyroxin from the thyroid gland

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The internal or hormonal secretion of a ductless gland

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Cells which secrete hormones directly into the blood, endocrine hormones always travel a long distance systemically to target cells.

Paracrine: Produced by a nearby cell and travels a very short distance as it is secreted in the ECF. Ie. Somatostatin – the all around "buzz killer" since it stops all activity as an inhibitor.

Autocrine: When a cell produces a regulator or hormone that then acts on itself. Ie. Prostaglandins.

Another View:
Denoting self stimulation through cellular production of a factor and a specific receptor for it

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Cells which produce a regulator or hormone which act upon itself.

Neurocrine: Can be Neural in that a neuron makes the hormone, secretes it into the ECF into the synaptic cleft and it travels a very short distance. These are the neurotransmitters like acetylcholine. Neural-endocrine is a combo of Neural and Endocrine in that the H is produced in a neuron and travels to the blood to get to its target tissue. Ie oxytocin.

Another View:  
Nervous cells have the ability to produce messenger molecules and hormones and secrete them into a synaptic cleft (acetyl choline, norepinephrine, epinephrine) or into the blood (oxytocin).

Amine: Organic molecules characterized by the presence of an amino acid group –NH2. Refers to the amine derivative types of hormone that begin as tyrosine. This then breaks down through a series of enzymatic reactions and converts to norepinephrine and epinephrine.

Another View:  
Endocrinologically some hormones are synthesized frome chemically derived amine substrates such as the amino acid tyrosine.

Peptide: These are the building blocks of proteins. Refers to another type of hormone synthesized from peptides, which are proteins. These are very large, take longer to synthesize and are more complex. The cell is stimulated and the hormone is produced first by gene transcription/replication to make a messenger RNA, which in turn makes a protein to make the hormone. These are made large and are then progressively cleaved before release into circulation. Prepro terms are used here. If using insulin as the hormone, for example, preproinsulin would be made which sends this hormone to the endoplasmic reticulum, cleaves the pre (which was the messenger to go to the ER), Proinsulin goes to the Golgi complex and is stored. The pro is cleaved here and when they are released both are released into circulation.

Another View:  
Bond occurring between amino acids, endocrinologically some hormones are poly-peptides comprised of amino acid chains.

Protein: The building blocks of the body! Amino acids, amine and amide derivatives all are proteins and the relationship to hormones is as above with the peptides.

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Protein hormones are produced as pre-pro-hormone molecules and may be stored for a quick response mechanism.

Steroid: Another class of hormones, which are derived from lipids. The steroids are made from cholesterol. The process to make steroids is very complex with multiple reactions occurring and lots of time to do so. They can’t be stored since they are so lipid soluble and can pass easily through the lipid bilayer cell membrane so steroids are made, as they are needed. They bind to plasma proteins in the blood, which lengthens their half-life. Examples are cortisol, vitamin D, and aldosterone

Another View:  
Lipid hormones often synthesized from cholesterol in a series of enzymatic reactions to produce hormones. (cortisol, vitamin D, aldosterol)

Binding protein: The steroids must bind with a protein to be transported easier through the blood. They bind onto albumin or globulin. Albumin is fairly nonspecific or nonselective and will bind with whatever. Globulin on the other hand is highly specific and selective and has a high affinity for what it binds to so it will bind very tightly to its hormone.

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Specific protein molecules found at target cells having a hich affinity to bind with specific hormones. May cause a conformational change in receptor complex, having a cellular effect downstream.

Plasma membrane receptor: The amine and protein hormones are not lipid soluble and cannot therefore cross the cell membrane. The plasma membrane receptor (ligand binding domain is that actual region on the receptor that the H bind to) are positioned on the outside of the cell membrane and are very specific binding sites for the hormones and will only respond when the right H attaches to it. This will cause a conformational change, which then activates it, and it can turn on the reaction in the cell specific for that hormone.

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An intrinsic protein receptor imbedded in the cell membrane, may be a channel for ion passage or part of a second messenger system with a binding site for a specific hormone or type of hormone.

Intracellular receptor: The outside receptor must be activated first and then the inside receptor can work. The dormant effector domain is on the inside and must be activated after the receptor on the outside has undergone its conformational change. Now this inside receptor undergoes its conformational change and activated the cell to respond to the original hormone

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Other types of receptor molecules or complexes which may be found in the cytosol, nuclear membrane, or nucleus. Hormones must cross the cell membrane to reach it’s receptor site.

Affinity: A substance’s attraction for another substance. When a substance has an affinity for another substance they can bind very tightly together.

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Tendency to favor bonding with specifically compatible chemical or molecular components such as receptors with specificity to bind only with certain hormones or messenger molecules. Condition producing affinity exists when both components are more chemically or electrically stable after binding.

Specificity: The quality of having a certain action, as of affecting only certain organisms or tissues, or reacting only with certain substances, as in receptor binding sites for specific hormones.

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The ability of chemical components to conditionally differentiate between molecules and bind or interact only with those it has an affinity towards.

RIA: Stands for radioactive immune assay. In endocrinology it is a method of measurement of hormone levels in the blood.

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A quantitative method for measuring hormone [conc.]
Takes advantage of competition between a tagged introduced hormone and the test subject’s natural hormone [conc.]. An RIA which is an antibody to the hormone is added to the sample in a measured quantity. Because the two hormone populations will compete for binding, and one is tagged, by measuring the amount of binding of the RIA to the tagged hormone we may determine the [conc.] of natural hormone through mathematical analysis.

Hyposecretion: Lack of or low hormone levels. It is a potential problem of the endocrine system and could be causes by an autoimmune dysfunction such as hypothyroidism – Hati Moto hypothyroidism or Type I DM where the body attacks the pancreas and you have decreased levels of insulin.

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Decreased levels of hormone secretion usually of autoimmune pathology, with a specific set of symptoms based upon hormone effects.

Hypersecretion: Too high levels of hormone. Causes could be from a tumor sitting on the adrenal gland and just keep stimulating it to put out cortisol, hyperplasia – increased cell growth, autoimmune stimulation – thyroid – an antibody binds to a receptor on the thyroid so the receptor thinks it is being stimulated and produces thyroid hormones and causes hypersecretion.

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Increased secretion may be stimulated by tumors, hyperplasia, or chronic autoimmune hyperstimulation, again having symptoms specific to elevated levels of hormone in question.

End organ insensitivity: This is a very hard to treat problem of the endocrine system. Ie insulin resistance – the H is produced but tissues don’t respond to it for some reason. It could be a receptor or downstream from the receptor where the H binds ok but the signal transduction or mechanism to turn of the cell has a defect so the cell doesn’t turn on and respond to the H. Therefore more H is produced since the message wasn’t received and so on.

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Decreased ability of target cells in an organ to respond to presence of hormonal messengers. Difficult to treat end organ insensitivity may be a function of pathological processes in receptor complexes, or downstream within the signal transduction mechanism.

Ectopic tumor: Another problem of the endocrine system – where and outside source such as a tumor sits elsewhere and secretes a Hormone. Ie the adrenal gland has an ectopic tumor in the lung that secretes the stimulatory H. The problem here is that there is no feedback so it just keeps on producing it and you have hypersecretion.

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Proliferative growth of cells NOT in the secreting gland, elsewhere in the body producing hormone without any feedback mechanism to control hormone production resulting in hypersecretion.

Define hormone and identify the varied modes of delivery:  A hormone is a powerful chemical messenger that has a physiological control effect on other cells of the body. Hormones can be delivered by endocrine, paracrine, autocrine or neural secretion as defined in the key words above.

Given the structural type of a hormone (protein, amine, steroid), describe its synthesis, secretion, and transport:  Proteins are synthesized by gene transcription/replication to make a messenger RNA, which in turn makes a protein to make the H. Most are made large and are progressively cleaved from preproH although not all peptides have pre some just have pro. The pre part sends the whole H to the endoplasmic reticulum, which cleaves off the pre and sends it to the Golgi complex which cleaves off the pro and then the H is stored and released when necessary. Protein H can’t pass through the cell membrane so they get there by secondary messengers or signal transduction. The H travels through the blood and binds to a receptor on the target cell, which is highly specific for each H. Once bound a series of reactions occur which travel into the cell to activate the cell. This system allows for amplification so very little H is needed originally to set off a whole series of reactions and the end result is quite large scale.

Amines are synthesized say in the adrenal medulla by beginning with tyrosine. A very rapid series of enzymatic reactions occur and you end up with norepinephrine and one more reaction will yield epinephrine. This takes seconds to occur. The amines are secreted and transported similar to proteins at this point.

Steroids are synthesized from cholesterol and are lipid soluble. A signal is received – the cell will either make cholesterol from inside itself or from other cells. It must process this cholesterol through a series of enzymatic reactions to make what you want. It is very involved and can even synthesize the enzymes themselves. It is time consuming since so many reactions occur. Steroids can’t be stored since they are lipid soluble and easily pass through the cell’s lipid bilayer membrane so steroids are generally made only as they are needed. Steroids also don’t travel in the blood well – like oil and water so they attach themselves on to plasma proteins albumin and globulin which greatly increases the steroids half life and ability to be soluble in the plasma and travel. Once the free steroid (unbound) gets to the target tissue it can just pass through the cell membrane and go to its receptor located in the cytosol or the nucleus of the cell. It binds and activates a receptor which diffuses into the nucleus, binds to a DNA and produces a protein

How are hormonal measurements made?:  Hormone levels are present in the blood is very minute amounts so you need a highly sensitive method of measuring them. You may also need to know the circadian rhythms that will determine when levels should be high or low on a daily/monthly basis. Measurements are made using RIA types to tag the hormones via competitive binding and measure the phosphorescence that is emitted or by enzyme activity. Another method is by measuring the rate of removal of the H from the blood, which is called the metabolic clearance rate. One could estimate the rate of hormone secretion by first measuring the concentration of natural H by using the RIA technique, then measure the metabolic clearance rate and multiply the [H] times the metabolic clearance rate. Since H levels change so rapidly one could really only get an accurate measurement by collecting samples of arterial blood entering the gland and venous blood leaving the gland and measuring the rate of blood flow through the gland.

Describe the four basic types of endocrinopathies:  These include hyposecretion, hypersecretion, end organ insensitivity, and ectopic tumor. See the key words above.

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Last Updated 04/10/00 12:27:00 PM