Carnegie 1

ENS communication system

slow, longer-lasting

ENS components of pathway

ductless glands – bloodstream or diffusion

ENS chemical messenger

hormones bind to target cell receptors

ENS effects

Upregulate or downregulate cellular responses

Classical endocrine mechanism

Target A → hormone production → bloodstream → target B → response

Autocrine mechanim

Target A → hormone production → target A → response

• cell make hormone that expresses that receptor too

Paracrine mechanism

Target A → hormone production → target b → response

• cell produces (hormone) close to target cell

• extracellular space

Neurocrine mechanism

Neuron → hormone production → bloodstream → target b → response

• neuron produces molecule that acts like hormone

What is a hormone?

chemical substance that is secreted in low quantities into the blood/ECF by a cell or grouping of cells and exerts a physiological effect on specific target tissues (or cells).

Hormones change the rates of ongoing chemical reactions for

• energy production & salt and water balance

• adaptive responses to help body cope with stress

• growth & development

• reproductive function

• RBC proliferation

• working with the ANS: circulation of blood; digestion & absorption of food

One hormone can have many actions

• testosterone

  • sperm formation

  • development of male reproductive tract

  • secondary sex characteristics

Many hormones can regulate a single process

• glucose ↔ glycogen

  • insulin

  • glucagon

  • thyroid hormones

  • epinephrine

  • cortisol

A single endocrine gland can produce more than one hormone

• Thyroid gland

  • Thyroxine

  • Triiodothyronine

  • Calcitonin

A single hormone can be produced by more than one endocrine gland

• Somatostatin

  • Hypothalalmus

  • Islet of Laangerhaan

  • gut

Hydrophilic hormones

includes peptides, proteins and the catecholamines

Lipophilic hormones

steroid hormones, also thyroid hormones

Solubility can determine or influence

• how they are made in the endocrine cell

• how they are transported

• where their receptors are located on target cells

• their mechanism of action

• their half-life

What are the 3 chemical classes of hormones?

• Amine

• Protein and peptides

• Steroid

Amine hormones

• smallest group and smallest molecule

• derivatives of tyrosine

• includes thyroid hormones (lipophilic) & catecholamines (hydrophilic)

Thyroid hormones

• Thyroxine (T4)

• Triiodothyronine (T3)

Catecholamines

• Norepinephrine

• Epinephrine

• Dopamine

Protein & Peptide Hormones

Hydrophilic

What is a prohormone? Why are they needed for peptide and protein hormones?

• substance that acts as a precursor to an active hormone

• In the body, it is converted into the final, biologically active form through enzymatic processes

• synthesized as inactive prohormones to allow for proper folding, transport, storage, and regulated activation, preventing premature action, ensuring stability, and enabling controlled release via enzymatic cleavage in the endoplasmic reticulum and Golgi apparatus before secretion as mature, active hormones. 

Why are cell surface receptors needed for peptide and protein hormones?

because these hormones are water-soluble (hydrophilic) and too large to pass through the cell's lipid membrane, so they must bind to receptors on the surface

Why are 2nd messengers needed for peptide and protein hormones?

• because they are unable to pass through the lipid bilayer of the cell membrane

Steroid Hormones

• derivatives of cholesterol (lipophilic)

• produced by adrenal cortex, gonads

Two other sources of steroid hormones under certain conditions?

• placenta

• adipose tissue (androgen to estrogen)

Groups of steroid hormones

• glucocorticoid (long term stress hormones)

• mineralocorticoids (produced by the adrenal cortex that regulate electrolyte balance (like sodium and potassium) and fluid levels, crucial for maintaining blood pressure and volume)

• sex steroids

Aromatase

converts androstenedione to estrone and testosterone to estradiol in gonads

How many rings does thyroid hormones have?

2

How many rings does catecholamines have?

1

How do peptides, proteins travel in the blood? are they water soluble?

• Circulate as free hormones

• water soluble

How does catecholamine travel in the blood? is it water soluble?

• are small – some are bound to plasma proteins, some are not

• water soluble

How does catecholamine travel in the blood? are they water soluble?

• free hormone + binding protein = hormone-protein complex

• not water soluble

What is physiologically more important? [bound hormone] or [free hormone]?

free hormone

• can come out of blood and act on target cell

Blood concentration of hormone depends on what?

rate of secretion (endocrine cell)

rate of clearance (liver, kidneys, target cell)

1) liver & kidneys are the primary metabolism and clearance organs

2) endocytosis of hormone-receptor complexes by targets; receptors recycled

3) peptides & catecholamines can be metabolized by blood-borne enzymes

4) steroid & thyroid hormones bound to proteins are less vulnerable

5) sometimes metabolism activates a hormone (e.g. testosterone → dihydrotestosterone; also the renin-angiotensin system)

Half-life

the time required for the plasma concentration of a hormone to decrease by 50%

What is the half-life of peptides/catecholamines versus steroid/thyroid hormones

peptides/catecholamines: fast (minutes)

steroid/thyroid hormones: slow (hours to days)

Describe the measurement of free hormone concentrations in biological fluids

• patterns of hormone secretion vary at certain times

What can you interpret from a single measurement of hormone concentration versus a time course of measurements?

pattern of secretion, helps map hormones

Ways to map hormone concentration

Radioimmunoassay or ELISA

• hormone attaches to bottom of dish

• 2nd anti: amplify levels

• increased colour = increased hormone

Hormone secretion occurs in response to

• Humoral regulation

• Neural regulation

• Hormonal regulation

Humoral regulation

Changes in plasma levels of minerals or organic nutrients are the signalling mechanism

Neural regulation

Release of NT

Hormonal regulation

Regulation by another hormone or neurohormone

Humoral Stimulus

Capillary blood contains low concentration of Ca2+ which stimulates...secretion of parathyroid hormone (PTH) by parathyroid glands*

Neural Stimulus

Preganglionic sympathetic fibers stimulate adrenal medulla cells....to secrete catechola- mines (epinephrine and norepinephrine)

Hormonal Stimulus

The hypothalamus secretes hormones that...stimulate the anterior pituitary gland to secrete hormones that...stimulate other endocrine glands to secrete hormones

Diurnal or circadian rhythm

• usually in response to the light/dark cycle

• what is happening is that the set-point around which the hormone concentration is fluctuating is dependent on the time of day

• key is the suprachiasmatic nucleus (located in hypothalamus) and the cyclical accumulation and degradation of clock proteins over a 24- hr period within those neurons

• SCN then influences daily rhythms of activity in various targets – e.g. the secretion of cortisol by the adrenal gland

Suprachiasmatic nucleus (SCN)

• The master biological clock

• Daylight: clock proteins (coded for by self-starting genes) are produced inside SCN neurons. Once a critical level is reached, they are transported into the nuclei of these cells.

• Inside the nucleus, they shut down the genes driving their production.

• At the same time, the clock proteins are gradually degrading.

• The cycle begins again as genes are once again able to self-activate to direct synthesis of new clock proteins in the SCN neurons.

• On its own, each cycle takes about 25 hr – we need a mechanism to adjust this slightly so that the SCN is reset each day to be on a 24-hr cycle

Light receptors in the retina help to establish what?

• a 24-hr rhythm

• Light arriving at a small subset of retinal ganglion cells leads to increased production of the visual pigment melanopsin (think of it as a light meter)

• The retinal ganglion cells then inform the SCN of the light level and that information is then transmitted to the pineal gland

• Secretion of melatonin by the pineal gland can increase up to 10x during darkness → induces natural sleep in concert with nighttime absence of light

Light hits eye → retinohypothalamic tract → suprachiasmatic nucleus → paraventricular nucleus → Intermediate cell column → superior cervical ganglion → pineal gland → melatonin