Adrenal Cortex - Hormones, Physiology

Question 1

• The adrenal glands lie on top of the …

Answer 1

kidneys

Question 2

• In the US - the adrenal glands are known as

Answer 2

suprarenal glands

Question 3

The adrenal glands are divided into inner adrenal… (10%) and the outer adrenal… (90%)

Answer 3

• inner adrenal medulla (10%) outer adrenal cortex (90%)

Question 4

The medulla is concerned with what response?

Answer 4

stress response

Question 5

The cortex is concerned with what response?

Answer 5

stress, sodium and glucose homeostasis

Question 6

• One part of the adrenal gland is required to be functional - this is essential for life
• what part is this?

Answer 6

The adrenal cortex must be functional!

Question 7

• The adrenal… synthesises many different hormones of a similar chemical structure (… hormones)
• Derived from … from the diet or synthesized within the gland itself.

Answer 7

• cortex (steroid hormones)
• derived from cholesterol from the diet

Question 8

What group of hormones are shown?

Answer 8

Steroid hormones

Question 9

The adrenal cortex is divided into three distinct layers, what are these?

Answer 9

1. Outer zona glomerulosa
2. Middle zona fasciculata
3. Innermost zona reticularis

Question 10

Cells within the different areas of the adrenal cortex possess different … and therefore synthesise different … hormones

Answer 10

Cells within the different areas of the adrenal cortex possess different enzymes and therefore synthesise different adrenocortical hormones

Question 11

Steroid hormones produce a variety of effects, but they are usually classified according to their predominant action, thus the major secretions of the adrenal cortex are the:

1. … (e.g. cortisol)
2. … (e.g. aldosterone)

Answer 11

1. glucocorticoids (e.g. cortisol)
2. mineralocorticoids (e.g. aldosterone)

Question 12

Synthetic pathway - adrenal cortex

• we start with … which feeds in, and is converted to pregnenolone
• Pregnenolone is then either converted into progesterone (what pathway?) or made into 17a OH Pregnenolone, which then goes into one of two pathways (… pathway or … pathway)

Answer 12

• we start with cholesterol -> converted to pregnenolone -
• Pregnenolone is then either converted into progesterone (mineralocorticoid pathway) or made into 17a OH Pregnenolone, which then goes into one of two pathways (glucocorticoid pathway or androgen pathway)

Question 13

• In the zoma glomerulosa, do we have the enzyme 17a-hydroxylase?
  
  • what does this mean?

Answer 13

• No - it is not present here hence cortisol and androgens cannot be synthesized in this layer, only aldosterone

Question 14

• In the zoma fasciculata and zona reticularis, do we have the enzyme 17a-hydroxylase?
• what does this mean?

Answer 14

• yes we do - it is present hence 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and the hormones derived from them.

Question 15

Androgens are synthesized where? (within adrenal cortex)

Answer 15

zona reticularis

Question 16

Cortisol is synthesized where? (within adrenal cortex)

Answer 16

zona fasciculata

Question 17

Aldosterone is synthesized where? (adrenal cortex)

Answer 17

zona glomerulosa

Question 18

• Under normal circumstances, the adrenal cortex secretes small quantities of male sex hormones (known as what?) such as dehydroepiandrosterone, androstenedione and testosterone, and the female …. e.g oestradiol
• these are only secreted in significant amounts in adrenal …

Answer 18

• Under normal circumstances, the adrenal cortex secretes small quantities of male sex hormones (androgens) such as dehydroepiandrosterone, androstenedione and testosterone, and the female oestrogens e.g oestradiol
• these are only secreted in significant amounts in adrenal disorders

Question 19

Synthesis, secretion and actions of the mineralocorticoids and the glucocorticoids are controlled …

Answer 19

independently

Question 20

Control of glucocorticoid secretion

• Hypothalamus releases … releasing hormone
• works on pituitary gland to release …
• goes to adrenal cortex and … cortisol production
• cortisol levels … - negative feedback mechanism - switching … CRH

Answer 20

• Hypothalamus releases Corticotrophin releasing hormone
• works on pituitary gland to release Adrenocorticotropic hormone (ACTH)
• goes to adrenal cortex and stimulates cortisol production
• cortisol levels rise - negative feedback mechanism - switching off CRH

Question 21

• The secretion of ACTH is pulsatile, meaning it peaks in the … at the time of … and is at it’s lowest point in …
• there is increased secretion in times of prolonged …
• disrupted by shift work and long-haul travel

Answer 21

• The secretion of ACTH is pulsatile, meaning it peaks in the early morning at the time of waking and is at it’s lowest point in the middle of the night
• there is increased secretion in times of prolonged stress

Question 22

Cortisol secretion shows the same pattern as secretion of …. but the peak and lowest point occurs approximately how much later than those of …

This pattern is related to sleep - meaning it is disrupted by what?

Answer 22

• ACTH
• Approx 2 hours later
• disrupted by shift work and long-haul travel

Question 23

Transport of glucocorticoids

• Only 10% of cortisol within the blood is in what form?
• is this form active or non-active?
• the remainder is bound to what? (give 2 examples and % found)

Answer 23

• Only 10% of cortisol within the blood is in free form
• is this form active or non-active? - active
• the remainder is bound to what? (give 2 examples)
  
  • plasma proteins - corticosteroid binding globulin (CBG or transcortin, 75%) and albumin (15%)
  • the same proteins also transport the other glucocorticoids and progesterone

Question 24

Pregnancy is associated with an increase in CBG which results in a compensatory increase in circulating plasma … concentrations

Answer 24

• cortisol
• the amount of free cortisol remains stable

Question 25

Metabolism of the adrenal steroids occurs mainly in the ... where they are ... to form water soluble forms which are excreted in ...

Answer 25

* **liver** * **glucuronidated** * excreted in **urine**

Question 26

In common with all other steroid hormones, glucocorticoids produce their effects by an action on ... receptors and alterations in gene expression: inevitably results in a ... in the order of hours or days

Answer 26

* In common with all other steroid hormones, glucocorticoids produce their effects by an action on **intracellular** receptors and alterations in gene expression: inevitably results in a **delay** in the order of hours or days

Question 27

In some cases the effects of cortisol are ... e.g. feedback inhibition of ACTH secretion

Answer 27

**rapid**

Question 28

At normal physiological concentrations the most important actions of cortisol are those on ... metabolism Cortisol works in an opposite way to Insulin, i.e. it ... 1. stimulates glycogeno... 2. stimulates hepatic ... 3. antagonizes the effects of insulin on cellular uptake of ...

Answer 28

* **carbohydrate** metabolism * Cortosil works in an opposite way to Insulin, i.e. it ... 1. stimulates glycogeno**lysis** 2. stimulates hepatic **g****luconeogenesis** 3. antagonizes the effects of insulin on cellular uptake of **glucoser**

Question 29

Cortisol also stimulates lipo... and mobilization of ...acids, partially by potentiating the effects of growth ... and the ...

Answer 29

* Cortisol also stimulates **lipolysis** and mobilization of **fatty** acids, partially by potentiating the effects of growth **hormone** and the **catecholamines**

Question 30

In excessive concentrations cortisol causes fat ... and deposition in novel anatomical sites, most notably the ... and the intrascapular region of the ...

Answer 30

In excessive concentrations cortisol causes fat **synthesis** and deposition in novel anatomical sites, most notably the **f****ace**and the intrascapular region of the**shoulder**

Question 31

* In the liver, cortisol stimulates amino acid ... leading to enhanced ... * In the periphery, it inhibits amino acid ... and protein ..., resulting in a net loss of ... protein

Answer 31

* In the liver, cortisol stimulates amino acid **uptake** leading to enhanced **gluconeogenesis** * In the periphery, it inhibits amino acid **uptake** and protein **synthesis,** resulting in a net loss of **skeletal** protein

Question 32

* Glucocorticoids are also able to stimulate ... receptors although ...-sensitive tissues possess an enzyme, 11B-hydroxysteroid dehydrogenase1, which converts cortisol to inactive ... * mineralocorticoid actions of glucocorticoids only apparent at ... concentrations

Answer 32

* Glucocorticoids are also able to stimulate **aldosterone** receptors although **aldosterone**-sensitive tissues possess an enzyme, 11B-hydroxysteroid dehydrogenase1, which converts cortisol to inactive **cortisone** * mineralocorticoid actions of glucocorticoids only apparent at **high** concentrations

Question 33

* Another effect of excess cortisol is an enhanced ... response to catecholamines which results in ... blood pressure

Answer 33

Another effect of excess cortisol is an enhanced **vasoconstrictor** response to catecholamines which results in **increased** blood pressure

Question 34

* Glutocorticoids also produce psychological effects with possible feelings of ..ation or ..dation

Answer 34

Glutocorticoids also produce psychological effects with possible feelings of **elation**or **sedation**

Question 35

At times of psychological and physiological stress (give examples of 3), there is a rapid secretion of ... and .... At these raised concentrations additional effects of these hormones become apparent

Answer 35

At times of psychological and physiological stress **(infection, trauma, hypoglycaemia)** , there is a rapid secretion of **ACTH** and **corticosteroids**. At these raised concentrations additional effects of these hormones become apparent

Question 36

**Glucocorticoids** affect the body's **defence** systems at many level. They may: 1. Suppress the ... tissue, reduce the ... production and inhibit the cellular immune ... 2. They stabilize leucocyte membranes and reduce the release of ... enzymes 3. They inhibit phospholipase A2 and reduce the synthesis of the inflammatory ....

Answer 36

They may: 1. Suppress the **lymphoid** tissue, reduce the **antibody** production and inhibit the cellular immune **system.** 2. They stabilize leucocyte membranes and reduce the release of **proteolytic** enzymes 3. They inhibit phospholipase A2 and reduce the synthesis of the inflammatory **mediators**

Question 37

There are many effects of **glucocorticoids**, but their most important role is in the response to ... In the **absence** of **corticosteroids** even mild ... can be fatal

Answer 37

**STRESS**

Question 38

At times of prolonged stress the glucocorticoids maintain the enhanced supply of ... which may be required for the prolonged response to the ... but they also suppress the ... response

Answer 38

At times of prolonged stress the glucocorticoids maintain the enhanced supply of **glucose** which may be required for the prolonged response to the **stressor** but they also suppress the **inflammatory** response

Question 39

_At times of injury:_ * ... alerts the sufferer to the damage * ... dilutes any toxic substances that may be present and immobilises and stabilises ... * Infiltration by ... destroys any invading cells whilst antibodies inactivate the foreign proteins * Tissue repair is enhanced by ...

Answer 39

* **Pain** alerts the sufferer to the damage * **Oedema** dilutes any toxic substances that may be present and immobilises and stabilises **joints** * Infiltration by **leucocytes** destroys any invading cells whilst antibodies inactivate the foreign proteins * Tissue repair is enhanced by **prostaglandins**

Question 40

* In preventing the processes of the inflammatory and immune responses it would appear that the **glucocorticoids**... the adverse effects of the injury and retard tissue repair * The ... thus appear to be acting contrary to the individual's best interests

Answer 40

* In preventing the processes of the inflammatory and immune responses it would appear that the **glucocorticoids** **potentiate** the adverse effects of the injury and retard tissue repair * The **steroids** thus appear to be acting contrary to the individual's best interests

Question 41

* The adrenocortical stress response decreases the ... response * It removes the pain and decreases the immobilization induced by the ... * ...-induced sedation also causes a lack of awareness of the severity of the situation * The overall effect is that the individual is able to perform despite the presence of the injury or infection

Answer 41

* The adrenocortical stress response decreases the **inflammatory** response * It removes the pain and decreases the immobilization induced by the **oedema** * s**teroid**-induced sedation also causes a lack of awareness of the severity of the situation * The overall effect is that the individual is able to perform despite the presence of the injury or infection

Question 42

_Summary of the physiological effects of cortisol_ * Stimulates release of amino acids from muscle * Increases ...lysis * Increases ...lysis * Increase ... levels * Increase ... pressure * Direct effects on ... and local effects on ...

Answer 42

* Stimulates release of amino acids from muscle * Increases **lipolysis** * Increases **glycogenolysis** * Increase **glucose levels** * Increase **blood** **pressure** * Direct effects on **brain** and local effects on **pain**

Question 43

_Control of mineralocorticoid secretion_ * What are the 2 physiologically important minceralocorticoids?

Answer 43

* **Aldosterone** and **11-deoxycorticosterone**

Question 44

* The major controlling factor in the secretion of aldosterone is the ... system * However ACTH stimulates the initial conversion of cholesterol to ...

Answer 44

* The major controlling factor in the secretion of aldosterone is the **renin-angiotensin** system * However ACTH stimulates the initial conversion of cholesterol to **pregnenolone**

Question 45

The secretion of aldosterone is also directly stimulated by what 4 things? What is it inhibited by?

Answer 45

1. trauma 2. anxiety 3. hyperkalaemia 4. hyponatraemia inhibited by atrial natriuretic peptide (ANP)

Question 46

_Actions of mineralocorticoids_ * Within the circulation aldosterone is only ...% protein bound * Aldosterone has specific ... receptors which cause expression of ion channels that transport ... and ... ions across the cell membrane

Answer 46

* Within the circulation aldosterone is only **50**% protein bound * Aldosterone has specific **intracellular** receptors which cause expression of ion channels that transport **sodium** and **potassium** ions across the cell membrane

Question 47

* Aldosterone stimulates the reabsorption of sodium ions in the ... tubule of the kidney, with some lesser effects in the ... duct, proximal ... and ascending ... of ..., and in the colon, sweat and ... glands * The sodium **reabsorption** occurs in exchange for either ... or ... ions

Answer 47

Aldosterone stimulates the reabsorption of sodium ions in the **distal** tubule of the kidney, with some lesser effects in the **collecting** duct, proximal **tubule** and ascending of **Henle**, and in the colon, sweat and **salivary** glands

Question 48

* By controlling reabsorption of sodium ions, aldosterone influences plasma .. concentration, which in turn influences water ... in the collecting duct via an effect on ... secretion. * The interaction of the ... system, aldosterone and ... therefore controls blood ... and influences ...

Answer 48

* By controlling reabsorption of sodium ions, aldosterone influences plasma .. concentration, which in turn influences water **reabsorption** in the collecting duct via an effect on **ADH** secretion. * The interaction of the **renin-angiotensin** system, aldosterone and **ADH** therefore controls blood **volume** and influences **blood pressure**

Question 49

_Pharmacological uses of adrenocorticosteroids_ * glucocorticoids (e.g. hydrocortisone = cortisol) are used in ... therapy * Also used for their immuno... or anti-.... effects in conditions such as ..., ... or allergies, or for the treatment of proliferative conditions such as ...

Answer 49

* glucocorticoids (e.g. hydrocortisone = cortisol) are used in **replacement** therapy * Also used for their immuno**suppressive** or anti-**inflammatory** effects in conditions such as **arthritis, asthma** or allergies, or for the treatment of proliferative conditions such as **leukaemia**

Question 50

_Pharmacological uses of mineralocorticoids_ * used only for ... therapy * ... plasma half-life of aldosterone renders it unsuitable for this purpose thus the drug of choice is ....

Answer 50

* used only for **replacement** therapy * **short** plasma half-life of aldosterone renders it unsuitable for this purpose thus the drug of choice is **fludrocortisone**

Question 51

* In most cases the selection of the glucocorticoid is dependent upon the ... of the available agents and the predominant effect required * Most glucocorticoids are ... active but their absorption through the ... varies as does their plasma ...

Answer 51

* In most cases the selection of the glucocorticoid is dependent upon the **pharmacokinetics** of the available agents and the predominant effect required * Most glucocorticoids are **orally** active but their absorption through the **skin** varies as does their plasma **half-life**

Question 52

_Many adverse effects are associated with the use of glucocorticoids, including:_ 1. Steroid usage may suppress ... healing and may exacerbate ... due to their immunosuppressant effects 2. Long term use in children may cause what? What about in adults? 3. The development of ... and other symptoms of ... syndrome also often accompanies steroid therapy The most important adverse effect, however, is the suppression of the ...-... axis Chronic administration of exogenous glucocorticoids results in suppression of ... secretion leading to atrophy of the adrenal ...

Answer 52

1. Steroid usage may suppress **wound** healing and may exacerbate **infections** due to their immunosuppressant effects 2. Long term use in children may cause what? - **inhibition of growth** What about in adults? - **osteoporosis** 3. The development of **diabetes mellitus** and other symptoms of **Cushing's** syndrome also often accompanies steroid therapy * The most important adverse effect, however, is the suppression of the **hypothalamic**-**pituitary** axis * Chronic administration of exogenous glucocorticoids results in suppression of **ACTH** secretion leading to atrophy of the adrenal **cortex**

Question 53

* If steroid therapy is then stopped abruptly, the adrenal cortex is unable to secrete endodenous hormones and the patient suffers with what? * How is this overcome

Answer 53

* **Addisonian crisis - may be fatal** * this consequence overcome by the **gradual** **reduction** of the dose of the **exogenous** **steroid**

Question 54

Anti-inflammatory ... remove the symptoms without affecting the cause of the underlying disorder, which may worsen

Answer 54

Anti-inflammatory **corticosteroids** remove the symptoms without affecting the cause of the underlying disorder, which may worsen

Question 55

_Core drug: Hydrocortisone (Cortisol)_ * Hydrocortisone is a natural ... secreted by the adrenal cortex * It acts via specific intracellular ... receptors to influence gene ... * Glucocorticoids are typically used for hormone ... therapy, as anti-inflammatory agents and immuno.... * Hydrocortisone is the drug of choice for this therapy

Answer 55

* Hydrocortisone is a natural **glucocorticoid** secreted by the adrenal cortex * It acts via specific intracellular **glucocorticoid** receptors to influence gene **expression** * Glucocorticoids are typically used for hormone **r****eplacement**therapy, as anti-inflammatory agents and immuno**suppressants** * Hydrocortisone is the drug of choice for this therapy

Question 56

_Core drug: Hydrocortisone (Cortisol)_ * Oral bioavailability? * protein binding? * metabolism? * half-life? * standard dose? * adverse effects? (3)

Answer 56

* Oral bioavailability - **60-80%** * protein binding - **high** * metabolism - **hepatic** * half-life - **approx 1.5** * standard dose - **15-20mg per day in divided doses** * adverse effects? (3) - **hyperglycaemia, osteoperosis, cushing's syndrome**

Question 57

Need to know for adrenal cortex - hormones, physiology * synthesis and actions of glucocorticoids, not including synthetic pathway details * actions of mineralocorticoids * therapeutic uses and adverse effects of corticosteroids

Answer 57

:)