Cher Endocrine Terms & Hormones

What is half-life?

A hormones life span can be expressed as its half-life, which is the amount of time it takes for 50% of circulating hormone to be removed from the circulation and excreted. Some hormones have a short half-life, whereas other hormones have a longer half-life.

Activated alpha subunits of G proteins can....

Activated alpha subunits of G proteins can also alter the activity of enzymes inside the cell. Ex: Activated alpha subunits can influence the rate of cAMP formation by activating or inhibiting adenylate cyclase.

Acute Hormone Secretion

Acute hormone secretion is represented by epinephrine, which is released in large amounts in response to stress or physical exercise. Thus, its concentration can change dramatically & irregularly, & its circulating levels differ with each stimulus. In addition, epinephrine usually circulates as a free hormone & has a short half-life.

G proteins that open Ion Channels Step 1

After a hormone binds to its receptor, the G protein is activated. The activated alpha subunit with GTP bound to it separates from the gamma and beta subunits.

G protein Step 2

After the hormone binds to its membrane-bound receptor, the receptor changes shape, and the G protein binds to it. GTP replaces GDP on the alpha subunit of the G protein.

What are autocrine chemical messengers?

An autocrine chemical messenger stimulates the cell that originally secreted it. (auto = self). Good examples of autocrine chemical messengers are those secreted by white blood cells during an infection. Several types of white blood cells can stimulate their own replication so that the total number of WBCs increases rapidly.

What is phosphodieterase?

An enzyme in the cytoplasm that breaks cAMP to AMP. Once cAMP levels drop, the enzymes in the cell are no longer stimulated.

Example of receptors that directly activate intracellular mediators...

Atrial natriuretic hormone, secreted by the heart atria, binds with its receptor in the plasma membrane of kidney cells. The result is an increase in the rate of cGMP synthesis at the inner surface of the plasma membrane. Cyclic GMP influences the action of enzymes in the kidney cells, which increases the kidneys' rate of Na+ & water excretion. The cGMP is present in the for only a limited amount of time because phosphodiesterase breaks down cGMP to GMP.

There are four classes of chemical messengers. What are they?

Autocrine chemical messengers Paracrine chemical messengers Neurotransmitters Endocrine chemical messengers

How do lipid soluble hormones travel?

Because of their small size and low solubility in aqueous fluids, lipid soluble hormones travel in the bloodstream bound to binding proteins. As a result, the rate at which lipid-soluble hormones are degraded or eliminated from the circulation is greatly reduced & their half-lives range from a few days to as long as weeks.

How do water soluble hormones travel?

Because water soluble hormones can dissolve in blood, many circulate as free hormones, meaning that most of them dissolve directly into the blood and are delivered to their target tissue without binding to a binding protein.

G protein Step 1

Before the hormone binds to its receptor, the G protein consists of three subunits, with GDP attached to the alpha subunit, & freely floats in the plasma membrane.

_________ occurs when a hormone is secreted that, in turn, stimulates the secretion of other hormones.

Hormonal stimuli The most common examples are hormones from the anterior pituitary gland, called tropic hormones.

What is another name for endocrine chemical messengers?

Hormones Endocrine glands secrete minute amounts of chemical messengers called hormones into the bloodstream, rather than into a duct. Hormones then travel to a distance from their source through the bloodstream to specific sites called target tissues or effectors, where they produce a coordinated response of the target tissues.

Blood-borne molecules can directly stimulate the release of some hormones. These molecules are referred to as _______.

Humoral stimuli They are called this because they circulate in the blood, and the word humoral refers to body fluids, including blood. These hormones are sensitive to the blood levels of a particular substance, such as glucose, calcium or sodium. Elevated blood glucose levels directly stimulate insulin secretion by the pancreas, & elevated blood potassium levels directly stimulate aldosterone release by the adrenal cortex.

What are the three types of stimuli that regulate hormone release?

Humoral, neural and hormonal. No matter what stimulus releases the hormone, however, the blood level of most hormones fluctuates within a homeostatic range through negative-feedback mechanisms. In a few instances, positive-feedback systems also regulate blood hormone levels.

Membrane-bound receptors & signal amplification: In the inactive & active states of G proteins.....

In the inactive state, a guanine diphosphate (GDP) molecule is bound to the alpha subunit of each G protein. In the active state, guanine triphosphate (GTP) is bound to the alpha subunit.

Because many water soluble hormones are quite LARGE or SMALL, they do not readily diffuse through the walls of all capillaries.

Large. They tend to diffuse from the blood into tissue spaces more slowly. On the other hand, other water soluble hormones are quite small & require attachment to a larger protein to avoid being filtered out of the blood.

Hormones fit into one of two categories. What are the two categories?

Lipid soluble hormones & Water soluble hormones, a distinction based on their behavior.

Lipid Soluble Hormones

Lipid soluble hormones are nonpolar, and include steroid hormones, thyroid hormones and fatty acid derivative hormones, such as certain eicosanoids (The eicosanoids are considered "local hormones." They have specific effects on target cells close to their site of formation).

What are the classes of receptors?

Lipid-soluble & water-soluble hormones bind to their own classes of receptors. 1. Lipid-soluble hormones bind to nuclear receptors. 2. Water-soluble hormones bind to membrane-bound receptors.

Lipid-soluble hormones bind to nuclear receptors.

Lipid-soluble hormones are relatively small. They diffuse through the plasma membrane and bind to nuclear receptors, which are most often found in the cell nucleus. They can be located in cytoplasm, but then move to the nucleus when activated.

Hormones that bind to binding proteins tend to have LONGER or SHORTER half-lives than hormones that do not require binding proteins.

Longer

Membrane-bound receptors & signal amplification: Receptors that activate G Proteins

Many membrane bound receptors produce responses through the action of G proteins.

Tropic Hormones

Many tropic hormones are part of a complex process in which a releasing hormone from the hypothalamus stimulates the release of tropic hormone from the pituitary gland. The pituitary tropic hormone then travels to a 3rd endocrine gland & stimulates the release of a 3rd hormone. For example, hormones from the hypothalamus & anterior pituitary regulate the secretion of thyroid hormones from the thyroid gland.

Membrane-bound receptors & signal amplification

Membrane bound receptors activate responses in two ways. 1) Some receptors alter the activity of G proteins at the inner surface of the plasma membrane. 2) Other receptors directly alter the activity of intracellular enzymes. These intracellular pathways elicit specific responses in cells, including the production of intracellular mediators.

Negative feedback

Most hormones are regulated by a negative feedback mechanism, whereby the hormone's secretion is inhibited by the hormone itself once blood levels have reached a certain point & there is adequate hormone to activate the target cell. This is a self-limiting system.

Two major mechanisms maintain hormone levels in the blood within a homeostatic range. What are they?

Negative feedback & Positive feedback

Following action potentials, neurons release a neurotransmitter into the synapse with the cells that produce the hormone. This type of hormone regulation involves ______.

Neural stimuli In some cases, the neurotransmitter stimulates the cells to increase hormone secretion. Some neurons secrete chemical messengers directly into the blood when they are stimulated, making these chemical messengers hormones. These hormones are neuropeptides.

Inhibition of Hormone Release by Neural Stimuli

Neurons inhibit targets just as often as they stimulate targets. If the neurotransmitter is inhibitory, the target endocrine gland does not secrete its hormone.

What are neurotransmitters?

Neurotransmitters are chemical messengers secreted by neurons that activate an adjacent cell, whether it is another neuron, a muscle cell or a glandular cell. Neurotransmitters are secreted into a synaptic cleft, rather than into the bloodstream. Therefore, in the strictest sense neurotransmitters are paracrine agents, but for our purposes it is most appropriate to consider them as a separate category.

Signal Amplificiation

Nuclear receptors work by activating protein synthesis, which for some hormones can take several hours. However, hormones that stimulate the synthesis of 2nd messengers can produce an almost instantaneous response because of the 2nd messenger influences existing enzymes. In other words, the response proteins are already present. Additionally, each receptor produces thousands of 2nd messengers, leading to a cascade effect & ultimately amplification of the hormonal signal.

Inhibition of Hormone Release by Humoral Stimuli

Often when a hormone's release is sensitive to the presence of a humoral stimulus, there exists a companion hormone whose release is inhibited by the same humoral stimulus. Usually, the companion hormone's effects oppose those of the secreted hormone & counteract the secreted hormone's action.

What are paracrine chemical messengers?

Paracrine chemical messengers act locally on nearby cells. These chemical messengers are secreted by one cell type into the extracellular fluid and affect surrounding cells. An example of a paracrine chemical messenger is histamine, released by certain WBCs during allergic reactions. Histamine stimulates vasodilation in nearby blood vessels.

G proteins that open Ion Channels Step 3

Phosphate is removed from the GTP bound to the alpha subunit. The alpha subunit can no longer stimulate a cellular response; it separates from the Ca2+ channel, and the channel closes.

Phospholipase C converts ____?

Phospholipase C converts phosphoinositol diphosphate (PIP2), a constituent of the plasma membrane, to DAG & IP3, which are released into the cytosol. DAG activates enzymes that synthesize prostaglandins, which increase smooth muscle contraction. IP3 releases Ca2+ from the enoplasmic reticulum or opens Ca2+ channels in the plasma membrane, allowing the ions to enter the cytoplasm & increase the contraction of the smooth muscle cells.

G proteins that open Ion Channels

Some activated alpha subunits of G proteins can combine with ion channels, causing them to open or close.

Receptors that directly alter the activity of intracellular enzymes.....

Some hormones bind to membrane-bound receptors & directly change the activity of an intracellular enzyme. The altered enzyme activity regulates the synthesis of intracellular mediators or results in the phosphorylation of intracellular proteins. The intracellular mediators or phosphorylated proteins activate processes that produce the cells' response to the chemical signals.

Receptors that Phosphorylate Intracellular Proteins....

Some hormones bind to membrane-bound receptors, & the portion of receptor on the inner surface of the plasma membrane acts as a kinase enzyme that phosphorylates several specific proteins.

Inhibition of Hormone Release by Hormonal Stimuli

Some hormones prevent the secretion of other hormones, which is a common mode of hormone regulation. For example, thyroid hormones can control their own blood levels by inhibiting their pituitary tropic hormone. Without the original stimulus, less thyroid hormone is released.

Positive feedback

Some hormones, when stimulated by a tropic hormone, promote the synthesis & secretion of the tropic hormone in addition to stimulating their target cell. In turn, this stimulates further secretion of the original hormone. This is a self-propagating system.

Membrane-bound receptors & signal amplification: Intracellular mediators

Some intracellular mediators are called second messengers. An intracellular mediator is a chemical produced inside a cell once a hormone or another chemical messenger binds to certain membrane bound receptors. The intracellular mediator then activates specific cellular processes inside the cell in response to the hormone. In some cases, this coordinated set of events is referred to as a second-messenger system.

Are phosphorylated proteins part of the membrane-bound receptor?

Some phosphorylated proteins are part of the membrane-bound receptor; others are in the cytoplasm of the cell. The phosphorylated proteins influence the activity of other enzymes in the cytoplasm.

Within the lipid and water soluble hormones they can be subdivided into groups based on their chemical structures. Name these groups.

Steroid hormones are those derived from cholesterol. Thyroid hormones are derived from amino acid tyrosine, while other hormones are categorized as amino acid derivatives, peptides and proteins.

Proteins, peptides and amino acid derivatives are all _____.

Water soluble hormones. They relatively have short half-lives because they are rapidly degraded by enzymes, called proteases, within the bloodstream. In many instances, protein and peptide hormones have a carbohydrate attached to them, or their terminal ends are modified. These modifications protect them from protease activity to a greater extent than water soluble hormones lacking such modifications. In addition, some water soluble hormones also attach to binding proteins & therefore circulate in the plasma longer than free water soluble hormones do.

Water-soluble hormones bind to membrane-bound receptors.

Water-soluble hormones are large & cannot pass through the plasma membrane, with their hormone-binding sites exposed on the plasma membrane's outer surface.

Membrane-bound receptors

When a hormone binds to a receptor on the outside of the plasma membrane, the hormone-receptor complex initiates a response inside the cell. Hormones that bind to membrane-bound receptors include proteins, peptides, & some amino acid derivatives, such as epinephrine & norepinephrine (water-soluble hormones).

Action of nuclear receptors: Nuclear receptors

When hormones bind to nuclear receptors, the hormone-receptor complex interacts with DNA in the nucleus or with cellular enzymes to regulate the transcription of particular genes in the target tissue. Thyroid hormones & steroid hormones bind to nuclear receptors (lipid-soluble hormones).

G protein Step 3

The G protein separates from the receptor. The GTP-linked alpha subunit activates cellular responses, which vary among target cells.

G protein Step 4

When the hormone separates from the receptor, additional G proteins are no longer activated. Inactivation of the alpha subunit occurs when phosphate (Pi) is removed from the GTP, leaving GDP bound to the alpha subunit.

Amplification

With amplification, a single hormone activates many 2nd messenger, each of which activates enzymes that produce an enormous amount of final product. The efficiency of the 2nd messenger amplification is virtually unparalleled in the body & can be thought of as an "army of molecules" launching an offensive. With amplification, one hormone has an army of molecules working simultaneously to produce the final products.

The binding of hormones to binding proteins is reversible. Hormones dissociate from their binding proteins at their target tissues and are then called ______.

free hormones It is important to note that some hormones always exist as free hormones because they do not have specific binding proteins to which they attach. The reversible binding of hormones to their binding proteins is important because only free hormones are able to diffuse through capillary walls and bind to target tissues.

G proteins that open Ion Channels Step 4

The alpha subunit recombines with the gamma and beta subunits.

G proteins that open Ion Channels Step 2

The alpha subunit with GTP bound to it binds to the Ca2+ channel, & the combination causes the Ca2+ channel to open. The Ca2+ diffuse into the cell & combine with calmoduliln. The combination of Ca2+ with calmodulin produces the cell's response to the hormone.

Action of nuclear receptors: mRNA

mRNA molecules move to the cytoplasm to be translated into specific proteins at the ribosomes. The newly synthesized proteins produce the cell's response to the hormone.

Chemical Messengers

Chemical messengers allow cells to communicate with each other to regulate body activities. Most chemical messengers are produced by a specific collection of cells by a gland. A gland is an organ consisting of epithelial cells that specialize in secretion, which is the controlled release of chemicals from a cell.

The three main patterns of hormone secretion are.....

Chronic hormone secretion Acute hormone secretion Episodic hormone secretion

Chronic Hormone Secretion

Chronic hormone secretion is exemplified by thyroid hormones, which vary in the blood within a small range of concentrations & remain relatively constant over long periods of time. Thyroid hormones are lipid soluble and thus bind to binding proteins, which helps maintain them at chronic levels.

Lipid soluble hormones are removed from the circulation when certain enzymes in the liver attach water-soluble molecules to hormones. This process is called ______.

Conjugation. These molecules are usually sulfate or glucuronic acid. Once the hormones are conjugated, the kidneys and liver excrete them into the urine and bile at a greater rate.

Give an example of a hormone that has a longer half-life.

Cortisol is a steroid hormone with a longer half-life, 90 minutes. Due to its lipid soluble nature, it is not easily degraded and can activate target cells for hours.

Example of cyclic AMP...

Cyclic AMP can elicit many different responses in the body because each cell type possesses a unique set of enzymes. Ex: The hormone glucagon binds to receptors on the surface of liver cells, activating G proteins & causing an increase in cAMP synthesis, which stimulates the activity of enzymes that break down glycogen into glucose for release from liver cells.

Cyclic AMP functions as what?

Cyclic AMP functions as a 2nd messenger, an intracellular mediator that carries out cellular metabolic processes in response to hormonal activation.

Receptors that Directly Activate Intracellular Mediators...

Cyclic guanine monophosphate (cGMP), an intracellular mediator, is synthesized in response to a hormone binding to a membrane-bound receptor. The hormone binds to its receptor, & the combination activates an enzyme called guanylate cyclase located at the inner surface of the plasma membrane. The guanylate cyclase converts guanine triphosphate (GTP) to cGMP & two inorganic phosphate groups. The cGMP molecules then combine with specific enzymes in the cytoplasm of the cell & activate them. In turn, the activated enzymes produce the cell's response to the hormone.

Down-regulation

Desensitization occurs when the number of receptors rapidly decreases after exposure to certain hormones. This happens because the cells' nutrient and energy supplies become depleted, causing the cells to lose the ability to respond to the hormone.

What are endocrine chemical messengers?

Endocrine chemical messengers are secreted into the bloodstream by certain glands and cells, which together constitute the endocrine system. These chemical messengers affect cells that are distant from their source.

Example of G proteins that open Ion Channels

Epinephrine activates alpha subunits to open Ca2+ channels in smooth muscle cells, allowing Ca2+ to move into those cells. The Ca2+ combine with calmodulin proteins, and the calcium-calmodulin complexes activate enzymes that cause the smooth muscle cells to contract. After a short time, the activated alpha subunit is inactivated because GTP is converted to GDP, & muscle contraction ceases. The alpha subunit then recombines with the beta & gamma subunits.

Episodic Hormone Secretion

Episodic hormone secretion is often observed in steroid reproductive hormones, which fluctuate over a month in cyclic fashion during the human reproductive years.

What is the difference between endocrine and exocrine glands?

Exocrine glands have ducts that carry their secretions to the outside of the body, or into a hollow organ, such as the stomach or intestines. Examples of exocrine secretions are saliva, sweat, breast milk, and digestive enzymes. (Endo = within)

Action of nuclear receptors: Hormone-response elements

The receptors that bind to DNA (lipid-soluble hormones bound with nuclear receptors) have fingerlike projections that recognize & bind to specific nucleotide sequences in the DNA called hormone-response elements.

Specificity

The tendency for each type of hormone to bind to one type of receptor, and not to others.

Membrane-bound receptors & signal amplification: What are the three G protein subunits?

From largest to smallest they are called alpha, beta and gamma. The G proteins are so named because one of the subunits binds to guanine nucleotides.

G proteins that activate other intracellular mediators...

G proteins can also alter the concentration of intracellular mediators other than Ca2+ or cAMP. Ex: Diacylglycerol (DAG) & inositol triphosphate (IP3) are intracellular mediators that are influenced by G proteins. Epinephrine binds to certain membrane-bound receptors in some types of smooth muscle. The combination activates a G protein mechanism, which in turn increases the activity of phospholipase C.

Up-regulation

This results from an increase in the rate of receptor molecule synthesis in the target cells.

Example of negative feedback

Thyroid hormones inhibit the secretion of TRH from the hypothalamus & TSH from the anterior pituitary.

Give an example of a hormone that has a short half-life.

Thyrotropin-releasing hormone (TRH) is a 3-amino-acid hormone with a short half-life. Because of TRHs composition, it is quickly degraded in the circulation and can activate only the target cells it can reach within 2 minutes of being secreted.

Example of Inhibition of Hormone Release by Humoral Stimuli

To raise blood pressure, the adrenal cortex secretes the hormone aldosterone in response to low blood pressure. However, if blood pressure goes up, the atria of the heart secretes the hormone atrial natriuretic peptide (ANP), which lowers blood pressure. Therefore, aldoesterone and ANP work together to maintain homeostasis of blood pressure.

Action of nuclear receptors: The combination of the hormone & its receptor forms a _____.

Transcription factor When the hormone-receptor complex binds to the hormone-response element, it activates the transcription of specific messenger ribonucleic acid (mRNA) molecules.

The length of time a hormone increases cGMP synthesis & has an effect on a cell is brief, once the hormone is no longer present. True or False?

True.

Lipid soluble hormones exhibit the 2 regular secretion patterns (chronic & episodic), whereas because of their short half-life water soluble hormones tend to exhibit the irregular (acute) secretion pattern. True or False

True. There are a few exceptions. Some protein reproductive hormones exhibit episodic secretion.

Depending on the enzyme phosphorylation increases or decreases the enzyme's activity. True or False?

True. The amount of time cAMP is present to produce a response in a cell is limited.

Intracellular enzymes controlled by membrane-bound receptors can be part of the receptor, or they can be separate molecules. True or False?

True. The intracellular mediators act as chemical signals that move from the enzymes that produce them into the cytoplasm of the cell, where they activate the processes that produce the cell's response. Ex: The hormone glucagon activates enzymes that release glucose into the circulation from cells within the liver.

Water Soluble Hormones

Water soluble hormones are polar molecules, they include protein hormones, peptide hormones, and most amino acid derivative hormones.

Example of Up-regulation

Increased number of receptors for luteinizing hormone (LH) in ovary cells during each menstural cycle. Follicle stimulating hormone (FSH) secreted by the pituitary gland increases the rate of LH receptor synthesis in ovary cells. This is important because a surge in LH will cause release of the egg.

Hormones from the hypothalamus that prevent the secretion of tropic hormones from the pituitary gland are called ______.

Inhibiting Hormones

Example of specificity

Insulin binds to insulin receptors, but not to recceptors for thyroid hormones. However, some hormones, such as epinephrine, can bind to a "family" of receptors that are structurally similar.

Example of phosphorylated proteins.

Insulin binds to its membrane-bound receptor, resulting in the phosphorylation of parts of the receptor on the inner surface of the plasma membrane & the phosphorylation of certain other intracellular proteins. The phosphorylated proteins enable the very powerful effect of insulin to allow glucose entry into cells.

What is adenylate cyclase?

It is an enzyme that converts ATP to cAMP.

Example of positive feedback

Prolonged estrogen stimulation promotes a release of LH.

What are protein kinases?

Protein kinases are enzymes that regulate the activity of other enzymes by attaching phosphates to them. A process called phosphorylation.

The portion of each receptor molecule where a hormone binds is called a _______.

Receptor site The shape and chemical characteristics of each receptor site allow only a specific hormone to bind to it.

Hormones exert their actions by binding to proteins called _____.

Receptors A hormone can stimulate only the cells that have the receptor for that hormone.

Some neuropeptides stimulate hormone secretion from other endocrine cells & are called _____.

Releasing hormones A term usually reserved for hormones from the hypothalamus.

Membrane-bound receptors & signal amplification: Cyclic Adenosine Monophosphate (cAMP)

cAMP is a common second messenger produced when a ligand binds to its receptor. Rather than the ligand entering the cell to activate a cellular process, cAMP stimulates the cellular process. Thie mechanism is usually employed by water-soluble hormones that are unable to cross the target cell's membrane.

Hormones requiring transport assistance bind to blood proteins called ______ and are called ______.

binding proteins; bound hormones. Hormones bind only to selective binding proteins. For example, thyroid hormones bind to a specific binding protein transthyretin; testosterone binds to testosterone-binding globulin; and progesterone binds to yet another type of binding protein called progesterone-binding globulin.

Example of AMP as a 2nd messenger.

cAMP binds to protein kinases & activates them.