Endocrinology Exam 1

Chemical Mediators

Those compounds or chemicals that regulate and transduce the behavior and physiological function of organisms, tissues, and cells

Earliest Endocrinological Study

Berthold, 1849

Used roosters; led to the discovery of testosterone; 4 experimental groups.

1. No surgery— the roosters had normal male traits/sexual behavior

2. Both testes removed— they lost normal male traits/sexual behavior (suggests something in the testes drives sexual maturation)

3. One testis placed in the abdominal cavity— the roosters had normal male traits/sexual behavior (suggests something in the testes circulates systemically)

4. One testis placed in the abdominal cavity— the roosters had normal male traits/sexual behavior (suggests something in the testes circulates systemically)

Shows us that testes do not need to be in their normal location to work; they just need a blood supply, which shows that the signal travels through the blood.

Endocrinology

The study of hormones

Bayliss and Starling

1902

1. They cut all nerves to the digestive organs.

2. Then they added dilute HCl to the small intestine to mimic acidic stomach contents.

3. Even without nerve connections, the pancreas still secreted buffers to neutralize the acid.

This showed that the intestine was releasing a chemical signal that traveled to the pancreas. That chemical was secretin, which is the first demonstrated hormone.

Endocrine Hormones

Chemical substances synthesized in specialized tissues or endocrine glands and released into the blood vasculature to act at a distance on another target tissue.

Paracrine Hormones

Agents or hormones that are synthesized and released from cells and act on adjacent cells. Occurs by diffusion of a chemical into an open system.

• Example: wound repair, growth hormone

Autocrine Hormones

Hormone secreted from a cell that influences the function of that cell (acts on self)

Neural Hormones

Neurotransmitters— diffuse short distance between neurons (e.g. acetylcholine, serotonin)

Neuroendocrine

Neurohormones, neuro-secretory hormones— Hormone released from neurons and carried by blood or other body fluids to act on distant cells.

• Example: thyroid releasing hormone, oxytocin, dopamine.

Ectohormones

Chemicals transported via air, water, or other external media to act between or among individuals.

2 types— Pheromones and Allelochemics (allomones)

Pheromones

Chemical interactions between individuals of the same species.

Allelochemics (allomones)

Chemical interactions between different species.

• Example: skunks

• commonplace among prokaryotes, plants, and invertebrates

• evidence exists that interspecies chemical signaling is also important for vertebrates

What is the new definition of hormone?

(used synonymously with chemical mediator)

Any substance synthesized and secreted by a cell to regulate another cell. May be delivered by the manner of endocrine, autocrine, paracrine, pheromonal route. Some chemicals can act in a variety of manners (e.g. endocrine, paracrine etc...)

Neurotransmitters (what is it derived from, hydrophobic/hydrophilic, implications of this)

• hormones synthesized and released from neurons (nonpeptidergic).

• derived from modified amino acids

• examples: dopamine, norepinephrine, serotonin

• Hydrophilic

  • Water-soluble, usually stored in vesicles, membrane receptors, short half-life, fast effects

Peptides (what is it derived from, hydrophobic/hydrophilic, implications of this)

• derived from chains of amino acids

• Hydrophilic

  • Stored in vesicles, cannot cross membrane, use membrane receptors + 2nd messengers, fast effects

• Peptides/proteins can be linear, rings, glycosylated, or consist of multiple peptide chains

When secreted from nerves, proteins are called ____?

When secreted from nerves, proteins are called neuropeptide hormones.

What is the most important component to determining the final shape of a peptide/protein hormone?

• The primary structure is the most important factor

• Primary structure includes the hormone’s amino acid sequence, its covalent backbone structure, and any interchain or intrachain disulfide bridges.

  • Interchain disulfide bridges connect different peptide chains.

  • Intrachain disulfide bridges connect different parts of the same peptide chain.

• This primary structure determines the hormone’s higher levels of protein structure: secondary, tertiary, and quaternary structure.

• Therefore, the hormone’s amino acid arrangement and covalent bonds ultimately determine its final shape.

T3 and T4 (what is it derived from, hydrophobic/hydrophilic, implications of this)

• Thyroxine (T4) and triiodothyronine (T3) are thyroid hormones that are made from the amino acid tyrosine. During their synthesis, inorganic iodine is added/incorporated into the hormone molecule.

• Hydrophobic

  • Lipid-soluble, use binding proteins, intracellular/nuclear receptors, long half-life, slower effects

Lack of iodine causes what health problem?

Iodine is required for thyroid hormone; not enough iodine causes hypothyroidism.

Steroids (what is it derived from, hydrophobic/hydrophilic, implications of this)

• Examples: estradiol, progesterone, testosterone, cortisol, aldosterone

• derived from cholesterol (lipids)

• Hydrophobic

  • Lipid-soluble, made as needed, carried by binding proteins, intracellular/nuclear receptors, slower effects

  • Very stable (unlike peptide bonds) which is why we can use a pill or patch to replenish them

Eicosanoids (what is it derived from, hydrophobic/hydrophilic, implications of this)

• derived from arachidonic acid (fatty acid)

• Examples: prostaglandins, thromboxanes, leukotrienes

• involved in smooth muscle contraction, inflammation, fever

Pheromones (what is it derived from, hydrophobic/hydrophilic, implications of this)

• Most pheromones are aliphatic derivatives.

• Aliphatic means they are made of hydrocarbon chains that can be:

  • saturated → like alkanes

  • unsaturated → like alkenes and alkynes

• This chemical structure helps make many pheromones volatile, meaning they can easily become airborne and be transported through the air.

• Some pheromones are different and are instead derived from nucleotides.

Growth Factors (what is it derived from, hydrophobic/hydrophilic, implications of this)

• Derived from mostly peptide hormones

• Therefore generally fit the hydrophilic peptide category

• Promote or inhibit cell division/mitogenic processes

• examples: insulin-like growth factors (IGF), transforming growth factor (TGF),

  epidermal growth factor (EGF)

Hydrophilic hormone properties

• Water/aqueous soluble

• Stored in vesicles (water soluble so it can’t diffuse through membrane lipid bilayer)

• Some have binding proteins (small molecules and some growth factors

  have binding proteins; for example, steroids). Most do not have binding proteins.

• Usually have short half-lives because most do not have binding proteins protecting them from degradation

  • half-life: time required to clear half the hormone from the blood

• Receptors are membrane bound (because hydrophilic molecules cannot permeate the lipid bilayer of the cell membrane)

• Mechanism of action is indirect— hormone effects are transduced via 2nd messengers (cyclic AMP, calcium, inositol triphosphate, kinases).

• Actions occur rapidly (seconds to minutes)

• Examples: peptide hormones, growth factors, neurotransmitters

Hydrophobic hormone properties

• Lipid soluble

• They are made as they are needed— no storage vesicles (exception of thyroid

• hormones).

• All have binding proteins (binding proteins help solubilize a hydrophobic molecule in an aqueous environment).

• Long half life— binding proteins increase half-life of molecule by preventing degradation of hormone.

• Receptors are cytoplasmic or nuclear (hormones can pass through cell membrane since they are lipid soluble, therefore there is no need for a membrane receptor).

• Mechanism of action is direct— directly elicits a cellular response

• Actions usually occur slowly (hours to days for a response to occur)

• Examples: steroids and thyroid hormones

What are the three factors that affect hormone activity?

plasma levels, clearance, and receptor abundance

Plasma levels of hormone

Plasma levels of hormone: result from tissue production (i.e. release) and blood clearance.

• Many hormones are initially produced as preprohormones and then

processed to produce mature (bioactive) hormone.

• Example: insulin

• It is free circulating levels of hormone that bind to target tissue

receptors. Hormones bound to binding proteins are not able to

bind receptors on target cells.

Clearance rate

• Clearance rate: how quickly a hormone is removed from the bloodstream.

• It depends on:

  • the hormone’s half-life— how long it takes for half of the hormone to be cleared

  • the hormone’s degradation rate— how quickly it is broken down

• Binding proteins increase a hormone’s half-life because they protect the hormone from being broken down, so it stays in the blood longer.

How are peptide and steroid hormones cleared from the blood?

Peptide hormones

• Are broken down, or cleaved, by enzymes called peptidases.

• This converts the peptides into inactive forms.

Steroid hormones

• Are modified mainly by the liver and kidneys.

• They are modified through processes such as sulfonation and glucuronidation.

• These modifications make the steroids inactive.

• The modified steroids are then removed from the body in urine.

Receptor Abundance

• A hormone can only cause an effect if the target tissue has receptors for that hormone.

• If there are no receptors, the hormone cannot trigger a cellular response.

• Hormones can also change receptor levels:

  • Up-regulation— increase the number of receptors

  • Down-regulation— decrease the number of receptors

• Laron dwarfs

  • These individuals have very high growth hormone (GH) levels.

  • Since GH normally stimulates growth, you would expect them to grow a lot.

  • But their GH receptor is mutated.

  • Because the receptor cannot properly transmit the GH signal, GH cannot produce its normal effect on body growth.

  • So even though there is plenty of hormone present, the body still does not respond normally because the receptor is defective.

Mechanisms of Hormone Control

• Negative feedback

• Positive feedback

• Cycle-dependent feedback