2A Hormone review

What are hormones?

Chemicals produced by endocrine glands; transported by the vascular system to alter the function of distant target cells.

What is a target cell? How do hormones affect target cells?

Hormones influence the production of enzymes or the rate of the enzymatic reactions. Hormones do not initiate reactions.

What physiologic functions are regulated by the endocrine system?

Metabolism (insulin, glucagon, calcitonin)

Growth (GH, thyroid hormone)

Reproduction (estrogens, progesterones, LH, FSH)

Describe cell-to-cell communication through paracrine communication.

Chemical synthesized & released by a cell, is diffused through surrounding extracellular fluid, and binds receptors on & alters the function of nearby cells.

Describe cell-to-cell communication through autocrine communication.

Chemical is synthesized and released by a cell, is diffused through surrounding extracellular fluid, and binds receptors on & alters the function of the same cell.

How are the endocrine and nervous systems similar, and how do they differ?

Both are responsible for coordinating & regulating physiologic systems.

Both utilize chemical messengers.

Neurocrine communication involves relatively short, rapid signals and response.

Endocrine communication involves relatively slow signals with prolonged responses.

Name the four hormone classes.

Proteins, Catecholamines, steroids, thyroid hormones

What does hormone class impact?

Synthesis, storage, release, transport, degradation & elimination, half-life, receptor types, therapeutic formulation & route of administration.

How are protein and peptide hormones synthesized?

Transcription (DNA → mRNA)

Translation (mRNA → protein)

After translocation, are the synthesized protein hormones biologically active?

No, inactive precursors must undergo 1-2 steps of post-translational modification in the RER, golgi, or secretory vehicles.

What is the difference between a preprohormone and a prohormone?

Preprohormones must undergo two steps of post-translational modification, while prohormones will undergo one step.

How is release of protein hormones regulated?

Secretory vesicles (granules)

How are secretory vesicles formed?

Occur when the hormones leaves the Golgi via vesicle budding.

How are protein hormones secreted?

Exocytosis of secretory vesicles. Either basal secretion, continuous low level. Or regulated secretion, in response to cellular signaling.

How does calcium mediate exocytosis of secretory vesicles?

following Ca influx into cytoplasm, Ca binds to synaptotagmin, stimulated fusion of vesicle membrane to plasma membrane via synaptobrevin to SNAP & syntaxin. Fusion leads to exocytosis.

What are steroid hormones derived from and what is their basic structure?

Derived mainly from cholesterol.

Lipophilic molecules with a 4-ring, 17-carbon backbone.

How do cells obtain and store cholesterol for steroid hormone synthesis?

LDLs enter cell via membrane receptors and are degraded via lysosomal enzymes to free cholesterol.

What is the rate limiting step of steroidogenesis? How is it mediated?

Cholesterol transfer from the outer to the inner mitochondrial membrane by StAR.

How is cholesterol converted to pregnenolone?

Side chain is cleaved from cholesterol in the mitochondria via cytochrome p450scc enzyme.

Where do the enzymatic modifications of pregnenolone occur during steroid hormones derived synthesis?

Within the mitochondria or smooth ER

What determines which steroid hormones leaves is ultimately synthesized by a cell?

Which enzymes are present in the cell.

Can steroid hormones be stored?

No, they must be released from the cell immediately after synthesis.

How are steroid hormones exported from cells?

The small, Lipophilic structure of hormones allows for simple diffusion across cell membranes.

Which hormones are derived from enzymatic modifications of tyrosine?

Catecholamines

Are Catecholamines “made to order”?

No, stored in secretory vesicles and released via exocytosis.

How are thyroid hormones synthesized?

Coupling & iodination of two tyrosine molecules

How are thyroid hormones stored?

Within colloid of thyroid follicles as part of the glycoprotein, thyroglobulin.

How are thyroid hormones released?

The lipophilic structure of these hormones allows for simple diffusion across cell membranes.

How are protein hormones transported?

Commonly circulate in their free, unbound form. Hydrophilic molecules and are readily dissolved in plasma.

How are thyroid hormones degraded?

Intracellular inactivation via endocytosis of hormone-receptor complexes & subsequent lysosomal degradation. AND extracellular inactivation where AAs are cleaved by peptidases associated with cell membranes or the ECF.

How are protein hormones ultimately eliminated from the body?

Excreted via urine

What is the half-life of protein hormones?

Relatively short (2-60 minutes)

Can be increased by peptide length, bonds, glycosylation, etc.

How are Catecholamines transported?

Hydrophilic molecules readily dissolve in plasma and can circulate in their free, unbound form or loosely bound to albumin.

How are Catecholamines degraded?

Intracellular inactivation via endocytosis of hormone-receptor complexed & subsequent lysosomal degradation.

How are Catecholamines excreted?

Excreted via urine

What is the held-life of catecholamines?

Short half-lives (only a few minutes)

How are steroid and thyroid hormones transported?

The lipophilic molecules have limited solubility in plasma, most circulate bound to plasma proteins.

What proteins bind and transport steroid and thyroid hormones in the blood?

Albumin - low affinity, high concentration

Steroid specific binding proteins - transcortin

Thyroid hormone-specific binding proteins - thyroid hormone-binding globulin

What is the half life of steroid & thyroid hormones?

Protein bound steroid hormones and thyroid hormones have a prolonged half life (hours to days).

How are steroids inactivated?

Conjugated with sulfates or glucuronides in the liver to inactivate and increase solubility.

How are steroid hormones excreted?

Excreted via urine or feces.

How are thyroid hormones degraded?

Deiodinated in bodily tissues. Also conjugated with sulfates or glucoronides in the liver.

How are thyroid hormones excreted?

Excreted in urine & feces.

Which classes of hormones utilize plasma membranes receptors?

Hydrophilic hormones (proteins, catelcholamines)

Which classes of hormones utilize cytoplasmic/nuclear receptors?

Lipophilic hormones (steroids, thyroid hormones)

Why can very low concentrations of a hormone produce a significant target-cell response?

Hormone receptors have a high affinity for their specific hormone

What is required for a hormone’s action to be terminated?

Decrease in plasma hormone concentration. And/or endocytosis of the receptor-hormone complex for internal degradation.

What determines the plasma hormone concentration, production or elimination?

The rate of hormone synthesis determines the plasma hormone concentration.