Intro to Endocrinology

Question 1

What are some methods of short-distance communication?

Answer 1

Autocrine regulation - cell secretes a hormone or chemical messenger that binds to autocrine receptors on that same cell, leading to changes in the cell.

Paracrine regulation - a paracrine regulator is a molecule or hormone produced by a tissue to regulate activity in that same tissue.

Juxtacrine regulation - a type of cell–cell or cell–extracellular matrix signalling in multicellular organisms that requires membrane contact.

Question 2

What are some methods of long-distance communication?

Answer 2

Neuronal transmission - Fast response & short-term effect.

Endocrine function - Chemical mediators released directly, diffuse into capillary and are transported via the blood stream to their target cells.

Question 3

What is a hormone?

Answer 3

Chemical messenger secreted directly into the blood stream and which acts often slowly, on distant organ and tissues.

Secretion of an endocrine gland that alters the physiological activity of target cells of the body.

Question 4

What is an endocrine gland?

Answer 4

A group of cells that secrete substances into the blood stream.

Question 5

What is an exocrine gland?

Answer 5

A group of epithelial cells that release products usually to a duct which deliver the secretion into an internal cavity or into an external surface of the body.

Question 6

What do hormones do on their target cells?

Answer 6

Alter their activity by stimulating selective receptors (membrane receptors or intracellular receptors).

Stimulate cell function (e.g. insulin stimulates glucose transport by muscles, glucocorticosteroid stimulates glucose synthesis).

Inhibit cell function (e.g. somatostatin inhibit growth).

Maintain ion levels (e.g. parathyroid hormone maintains blood calcium levels).

Stimulate or inhibit cell division (growth hormone or thyroid hormones stimulate growth and renewal of tissues).

Stimulate “programmed cell death” (apoptosis), or protect cells from this process.

Question 7

What are the missions of the endocrine system?

Answer 7

Maintaining the stability of the internal milieu (homeostasis).

Regulating a variety of body activities.

Question 8

What does the endocrine system regulate?

Answer 8

Growth, Development, Reproduction, Digestion, Blood pressure, Metabolism, Chemicals concentration in blood (and extracellular medium), Ions concentrations, Behaviour, Menstrual cycle.

Question 9

What are some types of target tissues?

Answer 9

Some circulating hormones affect many different types of cell in the body:

Growth hormone causes growth in most parts of the body.
Thyroid hormones increase metabolism in almost all of the body’s cells.

Some hormones affect only one specific target tissue:

Adrenocorticotropic hormone (ACTH) stimulates mainly only the adrenal gland 
Thyrotrophic hormone (TSH) stimulates only the thyroid gland. 
Gonadotropins have specific effects on sex organs (gonads) only.

Question 10

How is hormone secretion regulated?

Answer 10

Endocrine cells release their hormones in response to a selective stimulus associated with a body’s need.

Endocrine cells stop their secretion when the body’s need has been satisfied (regulation by feedback control).

Information regarding the hormone level or its effect is fed back to gland, which then regulate its secretion in an appropriated manner.

Examples: Blood glucose level and insulin secretion.

Question 11

How are hormones secreted?

Answer 11

Can be triggered by other hormones or neurotransmitters.

Can be pulsatile and follow a circadian rhythm.

Can be directly or indirectly commanded by the CNS (hypothalamus).

Question 12

How is hormone secretion related to the CNS?

Answer 12

Some endocrine secretions are partly commanded by the CNS.

Neurones can have endocrine function and deliver hormones to the blood stream (hypothalamus).

Some hormones are synthesised by both the CNS and peripheral organs (CCK, somatostatin, epinephrine).

Some endocrine cells, like neurones, can be depolarised.

The release of many hormones depends on this electrical activity.

Question 13

What are the different chemical classes of hormones:

Answer 13

Peptides.

Amino acid derivatives (mainly from tyrosine).

Lipid derivatives (mainly steroids from cholesterol).

Question 14

Where are thyroid hormones stored?

Answer 14

Not stored in dense granules.

Stored in the colloid of thyroid follicles within a glycoprotein (thyroglobulin).

Synthesis and release accelerated by hormonal stimulation (TSH).

Question 15

Where are peptide hormones stored?

Answer 15

Stored in dense granules (release Ca++-dependent).

Circulate free in the blood, sensitive to peptidase, short half-life (min to hours).

Interact with membrane receptors on the target cells

No tissue specificity.

Synthesised primarily as pro-hormone.

Question 16

How are peptide hormones released?

Answer 16

First synthesised as a preprohormone, with NH2 signal sequence, in endoplasmic reticulum.

Packaging in the Golgi of the prohormone, cleavage of signal sequences, possible further cleavages and glycosylation.

Final cleavage of the prohormone in dense granules.

Release of the hormones along with co-peptides via a Ca++ dependant process.

The process of maturation of a peptide hormone can be complex, a preprohormone peptide can be the precursors of different active peptides, depending on the maturation process.

Question 17

How does transport of hormones in blood work?

Answer 17

Steroids and thyroid hormones are lipophilic.

Carried in the plasma by globulins, sometimes very specific (eg: thyroid hormone binding protein, sex hormone binding protein) sometimes non specific (albumin).

Consequences:

Longer half-life.
Only the free fraction is active.

Question 18

What are the advantages of plasma protein binding?

Answer 18

Long-lasting effects developing progressively (slow rate of delivery to the target organs).

Additional pool of the hormone directly available.

Prevent the body from the effects of abrupt fluctuations in hormonal secretion.

Second protection against wastage (important for thyroid hormone).

The bound fraction serves as a circulating reservoir.

Question 19

What are some membrane receptors for hormones?

Answer 19

G-Protein-coupled receptors:

Stimulation of the receptor initiates a series of events which leads to the generation of second messengers within the cells.

The second messengers then trigger a series of molecular interactions that alter the physiology of the cell.

Tyrosine kinase receptors:

Receptors for insulin and Growth factors (insulin, insulin-like growth factors, growth hormone, prolactin).

The receptor is itself a protein kinase, it has only one transmembrane segment, kinase activity is switched on by binding of the hormone to the receptor.

Question 20

How do the tyrosine kinase receptors work?

Answer 20

Receptors directly coupled to kinase (insulin, growth hormone, prolactin, several growth factors).

The receptor is itself a protein kinase, it has only one transmembrane segment (possibility of dimerization for insulin receptor).

The kinase activity is switched on by binding of the hormone to the receptor.

Question 21

How do steroid and thyroid hormone receptors work?

Answer 21

Intracellular receptors in cytoplasm (steroids) or nucleus (thyroid hormones).

The complex hormone-receptor binds to the Response Elements (RE’s) in specific target genes (common sequence for all target genes of the hormone).

Then, the activated receptor induces changes in gene expression (stimulating or repressing).

Question 22

How can peptide hormones be applied therapeutically?

Answer 22

Used for replacement therapies, usually recombinant peptides, sometimes from other species, which can be slightly modified to increase or decrease their half-life, alter their stability, change their potency.

Drugs that can alter the secretion of a peptide hormone (some oral antidiabetic drugs like sulfonylureas stimulate insulin secretion).

Question 23

How can steroid hormones be applied therapeutically?

Answer 23

Wide range of agonists and antagonists, which can be very potent.

Problem: anti-inflammatory steroids have also metabolic effects.

For Thyroid hormones: replacement therapy by the hormones themselves.