Lecture 7.1 - The adrenal glands and the renin, angiotensin and aldosterone system

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Questions and Answers

What is the primary location where aldosterone promotes the expression of Na+/K+ pump?

Glomerulus of nephrons

Distal tubules and collecting ducts of nephrons (correct)

Juxtaglomerular cells of nephrons

Proximal tubules of nephrons

What is the primary function of the renin-angiotensin-aldosterone system?

Regulation of plasma cortisol concentration and immune response

Regulation of plasma sodium concentration and arterial blood pressure (correct)

Regulation of plasma glucose concentration

Regulation of plasma potassium concentration and heart rate

What is the effect of aldosterone on potassium ions in the kidney?

Increases excretion of potassium ions (correct)

Increases reabsorption of potassium ions

Decreases excretion of potassium ions

Decreases reabsorption of potassium ions

What is the primary location where aldosterone is synthesized and released?

Zona glomerulosa of the adrenal cortex Signup and view all the answers

What is the primary stimulus for the release of renin into the general circulation?

Decreased plasma Na+ or kidney blood flow Signup and view all the answers

What is the primary function of heat shock protein 90 in the context of glucocorticoid receptors?

Translocation of receptors to nucleus Signup and view all the answers

What is the primary binding site of aldosterone in the blood?

Serum albumin Signup and view all the answers

What is the primary tissue-specific effect of glucocorticoids?

Different effects on various tissues Signup and view all the answers

What is the primary function of the zona reticularis in the adrenal cortex?

To secrete weak androgens, such as DHEA and androstenedione Signup and view all the answers

Which of the following hormones partially regulates the secretion of DHEA and androstenedione?

ACTH and CRH Signup and view all the answers

What is the primary function of alpha-1 receptors in the adrenal medulla?

To facilitate an increase in intracellular Ca2+ Signup and view all the answers

Which of the following is NOT a response to the 'fight or flight' response stimulated by adrenaline and noradrenaline?

Increased insulin secretion Signup and view all the answers

What is the primary function of chromaffin cells in the adrenal medulla?

To release catecholamines into the circulation Signup and view all the answers

Which of the following is a response to adrenaline and noradrenaline stimulation in the central nervous system?

Increased mental alertness Signup and view all the answers

What is the primary function of beta-2 receptors in the adrenal medulla?

To increase cAMP levels Signup and view all the answers

Which of the following is a response to adrenaline and noradrenaline stimulation in the cardiovascular system?

Increased cardiac output Signup and view all the answers

What is the primary mechanism by which angiotensin II increases blood pressure?

Stimulating the adrenal cortex to secrete aldosterone, leading to increased sodium and water reabsorption Signup and view all the answers

What is the primary glucocorticoid hormone in humans?

Cortisol Signup and view all the answers

What is the effect of ACTH over-secretion on the adrenal cortex?

Adrenal hyperplasia and increased cortisol production Signup and view all the answers

What is the primary mechanism by which cortisol exerts its anti-inflammatory effects?

Inhibiting the production of inflammatory cytokines Signup and view all the answers

What is the effect of cortisol on proteolysis in most tissues?

Increased proteolysis Signup and view all the answers

What is the primary mechanism by which the renin-angiotensin-aldosterone system increases blood pressure?

Increasing sodium and water reabsorption in the kidneys Signup and view all the answers

What is the effect of angiotensin II on the adrenal cortex?

Stimulating the release of aldosterone Signup and view all the answers

What is the primary mechanism by which cortisol regulates its own secretion?

Negative feedback on the hypothalamus and anterior pituitary Signup and view all the answers

What is the effect of ACTH on the adrenal cortex?

Stimulating the release of cortisol Signup and view all the answers

What is the primary mechanism by which cortisol regulates glucose metabolism?

Increasing gluconeogenesis in the liver Signup and view all the answers

Study Notes

Heat Shock Protein 90

Receptor-ligand complex translocates to the nucleus
Dimerisation with other receptors can occur
Receptors bind to response elements (e.g. glucocorticoid response elements; GREs) or other transcription factors

Adrenal Cortex - Aldosterone

Aldosterone is the most abundant mineralocorticoid
Synthesised and released by the zona glomerulosa of the adrenal cortex
Lipophilic, so in blood, it binds mainly to serum albumin and to a lesser extent, corticosteroid-binding globulin (CBG)
Has intracellular receptors (aldosterone receptors: nuclear mineralocorticoid receptors)
Plays a central role in the regulation of plasma Na+, K+, and arterial blood pressure, and is a key component of the renin-angiotensin-aldosterone system (RAAS)
Mainly acts in the distal tubules and collecting ducts of nephrons in the kidney, promoting the expression of Na+/K+ pump, causing reabsorption of Na+ and excretion of K+, thereby influencing water retention, blood volume, and blood pressure

Renin-Angiotensin-Aldosterone System

RAAS regulates plasma sodium concentration and arterial blood pressure
If plasma Na+ or kidney blood flow falls, the juxtaglomerular cells of the nephrons are activated, releasing the enzyme renin into the general circulation
Blood pressure drop or blood volume loss can also stimulate the release of renin via baroreceptors in the carotid sinus
Renin acts on its target protein angiotensinogen, releasing angiotensin I
Angiotensin I is further cleaved to Angiotensin II by the angiotensin-converting enzyme (ACE) primarily within the capillaries of the lungs
Angiotensin II is the biologically active product of the RAAS
Angiotensin II:
- A potent vasoconstrictor, causing arterioles to constrict, resulting in increased arterial blood pressure
- Stimulates the adrenal cortex to secrete aldosterone
- Increases the release of antidiuretic hormone (ADH) from the posterior pituitary

Adrenal Cortex - Cortisol

Cortisol is the primary glucocorticoid hormone in humans
Synthesised and released by the zona fasiculata in response to ACTH
Inhibits CRH and ACTH release via negative feedback to the hypothalamus and anterior pituitary (HPA axis)
Lipophilic, so in blood, it is mainly bound to corticosteroid-binding globulin (CBG) and serum albumin
Acts via glucocorticoid receptors (intracellular receptors of the nuclear receptor family) which exert their actions by regulating gene transcription

ACTH Synthesis and Actions

ACTH is derived from pro-opiomelanocortin (POMC)
ACTH is hydrophilic and acts on high affinity G-protein coupled receptors (GPRCs) on the plasma membrane of target cells
GPRCs for ACTH are a type of melanocortin receptor (MC2) which use cAMP as a second messenger
ACTH binding to its receptors leads to activation of cholesterol esterase, increasing the conversion of cholesterol esters to free cholesterol, and also stimulates other steps in the synthesis of cortisol from cholesterol

Adrenal Cortex - Androgens

Dehydroepiandrosterone (DHEA) and androstenedione are weak androgens secreted by the zona reticularis
Partially regulated by ACTH and CRH
In males, DHEA is converted to testosterone in the testes
In females, adrenal androgens promote libido and are converted to oestrogens by other tissues

Adrenal Medulla

Adrenal medulla is a modified sympathetic ganglion of the autonomic nervous system (ANS)
Chromaffin cells in the adrenal medulla lack axons, but act as postganglionic nerve fibres, releasing catecholamines into the circulation
Catecholamines:
- Adrenaline (~80%) is used to treat anaphylaxis, since it causes vasoconstriction
- Noradrenaline (~20%)

Catecholamine Actions

Adrenaline and noradrenaline stimulate G-protein coupled receptors (GPCRs)
There are two main types of adrenergic receptors: alpha and beta
Adrenaline and noradrenaline have effects on the:
- Cardiovascular system (increased cardiac output, increased blood supply to skeletal muscles)
- Central nervous system (increased mental alertness)
- Carbohydrate metabolism (increased glycogenolysis in liver and skeletal muscles)
- Lipid metabolism (increased lipolysis in adipose tissue)

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Description

This quiz covers the regulation of hormone activity, including the role of heat shock protein 90, receptor-ligand complex translocation, and glucocorticoid response elements. It also touches on the synthesis and function of aldosterone in the adrenal cortex.