L06 - Adrenal Cortex: Hormones, Physiology

Question 1

Which part of the adrenal glands is essential for life

Answer 1

cortex

Question 2

what sort of hormone does the cortex synthesise

what are they derived from

Answer 2

The adrenal cortex synthesises many different
hormones of a similar chemical structure (steroid
hormones).

Derived from cholesterol from the diet or
synthesized within the gland itself.

Question 3

what are the 3 layers of the cortex and why do they secrete different hormones

Answer 3

The adrenal cortex is divided into three distinct layers:

Outer zona glomerulosa,
Middle zona fasciculata
Innermost zona reticularis.

Cells within the different areas possess different enzymes
and therefore synthesise different adrenocortical
hormones.

Question 4

What are the major secretions of the adrenal cortex?

eg of each

Answer 4

glucocorticoids
eg cortisol

mineralocorticoids
eg aldosterone

Question 5

what does each section produce?

Answer 5

zona glomerulosa:
18-hydroxylase enzyme hence aldosterone
synthesis.

zona fasciculata and zona reticularis:
17a-hydroxylase hence
17a-hydroxypregnenoIone, 17a-hydroxyprogesterone
and the hormones derived from them.

cortisol is synthesised in the zona fasciculata

androgens are synthesised in the zona reticularis.

Question 6

what else can the adrenal cortex secrete in small quantities?

when is this significant

Answer 6

Under normal circumstances the adrenal cortex
secretes small quantities of male sex hormones
(androgens) such as dehydroepiandrosterone,
androstenedione and testosterone, and the female
oestrogens eg oestradiol.

Only significant in adrenal disorders.

Question 7

how is GLUCOCORTICOID secretion controlled?

Answer 7

controlled independantly of mineralocorticoids.

hypothal: CRH
then
ant pit gland: ACTH
then
adren. cortex: cortisol

cortisol feeds back to hypothal

Question 8

What are the the secretion patterns of ACTH and cortisol like?

what is it related to and how is it disrupted?

Answer 8

The secretion of ACTH is pulsatile:
–peak in the early morning, at the time of waking
—nadir in the middle of the night.
Increased secretion at time of prolonged stress.

Cortisol secretion shows the same pattern but the peak
and nadir occurs approximately 2 hours later than those of
ACTH.

This pattern is related to sleep - wake patterns: disrupted
by shift work and long-haul travel.

Question 9

GLUCOCORTICOID transport

how does it travel in the blood

Answer 9

Only 10% of cortisol within the blood is in a free, active form,
the remainder is bound to the plasma proteins:

corticosteroid binding globulin (CBG or transcortin) (75%)

albumin (15%)

The same proteins also transport the other glucocorticoids and
progesterone.

Question 10

how does pregnancy effect cortisol and its transport

Answer 10

pregnancy associated with CBG increase

compensatory incr in plasma cortisol conc.

amount of free cortisol remains stable

Question 11

where are adrenal steroids metabolised and what happens to them

Answer 11

mainly occurs in liver

are glucuronidated to water soluble forms, excreted in urine

Question 12

how do GLUCOCORTICOIDS (and all other steroid hormones) have their effect

how long does this take

Answer 12

Via action on intracellular receptors and alterations in gene expression

this results in a delay of hours of days

but effects of cortisol can be rapid in some cases - eg feedback inhibition of ACTH secretion

Question 13

GLUCOCORTICOID / CORTISOL

Actions: OVERVIEW - places and what

Answer 13

• • oppose insulin
• • Liver (aa)
• • periphery (aa)
• • stim aldosterone tissues (at high)
• • enhanced vasoconstricter responses to catcholamines
• • feeling of elation
• • affect body defence systems
• • prolonged stress: enhanced supply of glucose and inflamm response suppressed

Question 14

Cortisol:

Effect on carb metabolism & fat & amino acids

Answer 14

Oppose insulin
stim glycogenolysis
stim hepatic gluconeogenesis

also lipolysis and mobil of FA – via potentiating effect of GH and catcholamines

XS conc, causes fat synthesis and deposition at novel sites – face, intrascapular region

aa:
LIVER: aa uptake – enhanced gluconeogenesis
PERIPHERY: inhibits aa uptake and protein syn – net loss of skeleton

Question 15

GLUCOCORTICOIDS: stim of aldosterone receptors.

regulation and when

Answer 15

They posses 11β-HSD which inactivates cortisol to cortisone.

only at high conc

Question 16

XS cortisol: vasoconstriction effect

what happens, how

Answer 16

enhanced vasoconstrictor responses to catecholamines

Question 17

Glucocorticoids: psychological feelings

Answer 17

elation, sedation

Question 18

when do additional effects of glucocorticoids become more apparent?

examples? how does this happen?

Answer 18

times of psychological and physiological stress
eg trauma, infection, hypoglycaemia

leads to rapid secretion of ACTH and corticosteroids

Question 19

Glucocorticoids and body defence mechanisms

how does it effect it

Answer 19

• -suppress lymphoid tissue, reduce antibody production and inhibit cellular immune system
• -stabilise leucocyte membranes and reduce proteolytic enzyme release
• • inhibit phospholipase A2 and reduce inflam mediators synthesis

Question 20

Glucocorticoids: response to stress

what happens at prolonged stress

Answer 20

most important

prolonged stress - maintain enhanced supply of glucose & suppress inflam response

• –removes pain, decr immobilisation induced by oedema
• –steroid induced sedation –> lack of awareness of the severity of the situation
• – overall effect is that the individual is ale to perform despite injury/infection

Question 21

MINERALOCORTICOIDS

what are the most important ones

how are they controlled

what is it stim by

Answer 21

Aldosterone and 11-deoxycorticosterone

ACTH stimulates initial conversion of cholesterol to pregnenolone but aldosterone is relatively ininfluenced

major control: renin-angiotensin system

stim by trauma, anxiety, hyperkalaemia, hyponatraemia, INHIB by ANP

Question 22

Mineralocorticoids: actions

how much is protein bound
what does it do

Answer 22

50% protein bound

aldosterone have sp intRAcellular receptors

these cause expression of ion channel that transport Na and K across cell membrane

also stim reabsorptio of Na ions in DT of kidney. (some in CD, prox tub asc,LOH, colon, swear, sal gland)
—Na reabsorption exch. for K or H ions

Question 23

Mineralocorticoids and blood pressure

Answer 23

aldosterone reab of Na, which influences plasma Na conc
—> influences water reab in CD via an effect on ADH secretion

interaction of renin-angiotensin system, aldosterone and ADH controlls blood vol&pressure

Question 24

Adrenocorticosteroids

Pharmacological uses

Answer 24

Glucocoticoids
—- eg hydrocortisone = cortisone

replacement therapy, for immunosuppressive or anti inflam effect

eg for asthma, allergies, arthritis, or for treatment of proliferative conditions eg leukaemia

MINERALOCORTICOIDS

eg FLUDROCORTISOL

used replacement therapy only.
short plasma half life of aldosterone means it can’t be used – so drug is^

Question 25

Use of Glucocorticoids in therapy

what is the selection of them dep on

adverse effects of glucocorticoids?

Answer 25

Dep on pharmacokinetics of the available agents and predominant effect required

Most glucocorticoid are orally active — but absorption through skin varies as does plasma half life

adverse effects:
– steroid use may suppress wound healing, may exacerbate infections due to immunosuppressant effects
–LT use in children may inhibit growth, in adults may result in osteoporosis
– dev of DM, other symp of Cushing’s
– MOST IMPORTANT:
—–supression of hypothalamic pituitary axis
—->
chronic admistration of exogenous corticoids results in suppression of ACTH secr —> atrophy of adrenal cortex.
If stopped abruptly,

Question 26

What happens if steroid therapy is stopped abruptly?

Answer 26

Adrenal cortex can’t secr endogenous hormones –> addisonian crisis –> may be fatal

consequence can be overcome by gradual reduction of exogenois steroid growth

Menstrual disturbances

also

anti inflam corticosteroids remove the symptoms without affecting cause of underlying disorder, which may worsen.

Question 27

Core Drug: Hydrocortisone (cortisol)

what is it?
what is it used for?
adverse effects?

Answer 27

a glucocorticoid secr by adrenal cortex.
acts via sp intracellular glucocorticoid receptors – influence gene expression

used for hormone replacement therapy, anti inflam and immunosuppress

drug of choice for replacement therapy

adverse – hyperglycaemia, osteoporosis, cushing’s