Endocrine signaling-- The action hormones

Where/what is the

hypothalamus?

Hint: what does hypo mean?

Below thalamus—important for homeostasis

Where/what is the Adrenal glands

toward the kidney (on top)— produce hormones,, has a cortex and bottom medulla section

What does the cortex of the adrenal glands produce?

Mineralocorticoids (Aldosterone), Glucocorticoids (Cortisol, and Androgens)

Medulla produces

epinephrine & norepinephrine.

What does aldosterone do ? (simple)

• Regulates blood osmolality, by reabsorption of sodium by kidney, ad excretion of K+

• Controls Na⁺ (sodium) and water balance

• Causes kidneys to retain sodium and water

• Helps maintain blood volume and blood pressure

👉 Mineralocorticoid = salt/water balance

What do glucocorticoids do?

• Main one: Cortisol

• Raises/maintains blood glucose

• Helps the body respond to stress

• Also affects metabolism and decreases inflammation

👉 Glucocorticoid = glucose + stress

Aldosterone (complex)

Aldosterone is a ligand that binds MR receptor dimerizes, and activates ENact, Na/Kpump, and SGK1 which phosphrylates Nedd4=2 and deactivates it.

Aldosterone increases Na⁺ reabsorption and K⁺ excretion by increasing ENaC and Na⁺/K⁺ pump activity. It also activates SGK1, which inhibits Nedd4-2 by phosphrylating it and prevents ENaC from being destroyed. This allows more Na⁺ to be reabsorbed into the blood, causing water to follow by osmosis and increasing blood volume and blood pressure.

What is Connn’s syndrome/ Primary Aldosteronism

Overproduction of aldosterone, Headache

• Hypokalemia

• Muscle cramps/weakness

guess diagnosis: “I’ve been having persistent headaches

and muscle cramps, and my blood pressure won’t

go down even with medication.”

Conn’s Syndrome Case Study

guess diagnosis:

1-year history of treatment-resistant hypertension

despite being on 3 antihypertensives

• Frequent headaches, occasional palpitations,

fatigue, and muscle weakness

• Recent episodes of numbness and tingling in fingers

• No history of diabetes or kidney disease

(do a CT scan for adenoma for adrenal adenoma,)

What does MR mean in terms of Adrenal gland

Mineralcorticoid Receptor

Cortisol (big picture)

• Increase blood glucose → gives you energy

• Increase blood pressure → helps maintain circulation

• Reduce inflammation → prevents the immune response from becoming excessive

Cortisol (Complax)

Cortisol is a ligand that diffuses into the cell, binds to the GR (receptor), undegoes nuclear translocaiton and then gene activation. (increases lipocortin-1, which is an anntiinflammatory—destroys neutrophils., increases PEPCK (GNG), and IL-1, and TNA-a (inflammatory)

Cortisol is a glucocorticoid and stress hormone that increases blood glucose by increasing PEPCK, an enzyme involved in gluconeogenesis, which produces new glucose. It also helps maintain blood pressure and has anti-inflammatory effects by increasing lipocortin-1 and suppressing inflammatory molecules such as TNF-α.

Cortisol → vasoconstriction → ↑ BP

What does lipocortin-1 do?

supress integrins on neutrophils—less binding to ICAM, (anti-inflamation)

How does TNF-A promote inflammation

TNF-alpha binds TNF alpha receptor, which degrades the inhibitor of NFkb, and therefore activates the inflammatory response,

however, cortisol will surpress TNF-alpha,