Endocrine Monday, Wk 3

What is the main glucocorticoid?

cortisol (hydrocortisone)

Main job of cortisol is to?

combat stress

How does cortisol fight stress?

increase blood glucose and increase blood pressure

Cortisol inhibits ______ and ______, and suppresses _____.

swelling and inflammation; immune system

What two types of cells are shut down in the double negative feedback?

parvocellular neurons and corticotroph cells

Cortisol exerts ____% of all glucocorticoid activity.

95%

Cortisol also has a significant amount of ______ activity.

mineralocorticoid

The plasma concentration of cortisol is _____ than that of aldosterone.

greater

What percentage of cortisol floats free in the blood?

10%

90 % of cortisol is carried in the bloodstream via ________.

corticosteroid binding globulin or transcortin

Cortisol binds with high affinity to _______.

α-glucocorticoid receptor

AKA for α-glucocorticoid receptor

GR-receptors or type II corticosteroid receptors

What binds to and deactivates the cortisol receptor until cortisol shows up?

heat-shock protein 90

T/F: Cortisol binds to β-glucocorticoid with same affinity as it binds to α-glucocorticoid.

F - low affinity

T/F: Renal cells have a high amount of an enzyme called 11β-hydroxysteroid dehydrogenase type 2.

T

____ binds to all the cortisol that enters the kidney.

11B-HSD2

The binding of 11B-HSD2 to cortisol turns into a less biologically active molecule called ______.

cortisone

What is AMES?

a rare autosomal recessive disease, due to a mutated 11β-HSD2 gene

What happens to the MR receptors in a patient that has AMES?

MR receptors get double stimulated by aldosterone and cortisol

Hypernatremia (hyperosmolalic) blood triggers the release of _____ from ______ neurons.

ADH (vasopressin); magnocellular neurons

Too much sodium comes in to the principal cell and immediately kicked out the basolateral surface via...

sodium-potassium ATPase

Does Na level increase or decrease in a patient that has AMES?

increase

The ADH (vasopressin) binds to _____ receptors on principle cells which causes _____ implantation on the apical membrane, to allow for lots of water to rush down its concentration gradient.

V2; aquaporin 2 receptor

Since the thick ascending limb of Henle has no aquaporin channels, it means it can only reabsorb sodium ion.s This would make the filtrate...

hypotonic (water rich)

Tons of water into the blood fixes hypernatremia but often cause ______.

hypertension

How do AMES patients clinically present?

as if they have hyperaldosteronism

low/normal levels of aldosterone

hypertension

hypokalemia

metabolic alkalosis

_______ have MR receptors within the cytosol.

alpha intercalated cells

Binding of aldosterone (or excessive cortisol) stimulates the production and insertion of two types of hydrogen ion transporters on the apical surface, which are?

H/K-pump ATPases and hydrogen ATPases

______ is also stimulated to produce not only hydrogen ion from CO2 and water, but also _____.

carbonic anhydrase; bicarbonate

Metabolic alkalosis occurs because of _____ release into the urine (filtrate) and _____ release into the bloodstream.

hydrogen ions; bicarbonate

In large amounts, ______ blocks 11β-HSD2, therefore ______ will not be converted to cortisone.

glycyrrhetinic acid; renal cortisol

The glucocorticoids are

cortisol; corticosterone; cortisone; prednisone; methylprednisolone; dexamethasone; hydrocortisone

Corticosterone is a glucocorticoid yet it is in what pathway?

mineralocorticoid (aldosterone) pathway

Synthetic glucocorticoids were first used as a treatment for ______ but are now commonly used for all sorts of ______ conditions.

rheumatoid arthritis; inflammatory

The most potent glucocorticoid is?

dexamethasone

How do glucocorticoids knock out inflammation in over-inflamed tissue?

genomic and non-genomic mechanisms

genomic effects of glucocorticoids

-Turns off (transrepression) genes in pro inflammatory cells

-Turns off creation the of arachidonic acid by blocking action of phospholipase A2 (PLA2)

-Turns on (transactivation) genes in some leukocytes which make anti-inflammatory cytokines

Pro-inflammatory cytokines

IL-1,IL-2, IL-6, IL-8, (tumor necrosis factor) TNF-alpha, interferon gamma

anti-inflammatory cytokines

IL-10, NF-kB inhibitor, lipocortin-1

Lysosomal destruction releases destructive substances which fuel inflammation and damaged tissue. _____ prevents lysosomes from releasing substances, which will ______

cortisol; decrease inflammation

Cox-1 inhibitors will inhibit the creation of _____ which will eventually lead to _____.

PGE2; ulcers