L06 - Adrenal Cortex: Hormones, Physiology Flashcards
Which part of the adrenal glands is essential for life
cortex
what sort of hormone does the cortex synthesise
what are they derived from
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.
what are the 3 layers of the cortex and why do they secrete different hormones
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.
What are the major secretions of the adrenal cortex?
eg of each
glucocorticoids
eg cortisol
mineralocorticoids
eg aldosterone
what does each section produce?
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.
what else can the adrenal cortex secrete in small quantities?
when is this significant
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.
how is GLUCOCORTICOID secretion controlled?
controlled independantly of mineralocorticoids.
hypothal: CRH then ant pit gland: ACTH then adren. cortex: cortisol
cortisol feeds back to hypothal
What are the the secretion patterns of ACTH and cortisol like?
what is it related to and how is it disrupted?
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.
GLUCOCORTICOID transport
how does it travel in the blood
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.
how does pregnancy effect cortisol and its transport
pregnancy associated with CBG increase
compensatory incr in plasma cortisol conc.
amount of free cortisol remains stable
where are adrenal steroids metabolised and what happens to them
mainly occurs in liver
are glucuronidated to water soluble forms, excreted in urine
how do GLUCOCORTICOIDS (and all other steroid hormones) have their effect
how long does this take
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
GLUCOCORTICOID / CORTISOL
Actions: OVERVIEW - places and what
- 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
Cortisol:
Effect on carb metabolism & fat & amino acids
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
GLUCOCORTICOIDS: stim of aldosterone receptors.
regulation and when
They posses 11β-HSD which inactivates cortisol to cortisone.
only at high conc
XS cortisol: vasoconstriction effect
what happens, how
enhanced vasoconstrictor responses to catecholamines
Glucocorticoids: psychological feelings
elation, sedation
when do additional effects of glucocorticoids become more apparent?
examples? how does this happen?
times of psychological and physiological stress
eg trauma, infection, hypoglycaemia
leads to rapid secretion of ACTH and corticosteroids
Glucocorticoids and body defence mechanisms
how does it effect it
- -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
Glucocorticoids: response to stress
what happens at prolonged stress
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
MINERALOCORTICOIDS
what are the most important ones
how are they controlled
what is it stim by
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
Mineralocorticoids: actions
how much is protein bound
what does it do
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
Mineralocorticoids and blood pressure
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
Adrenocorticosteroids
Pharmacological uses
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^
Use of Glucocorticoids in therapy
what is the selection of them dep on
adverse effects of glucocorticoids?
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,
What happens if steroid therapy is stopped abruptly?
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.
Core Drug: Hydrocortisone (cortisol)
what is it?
what is it used for?
adverse effects?
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
