Adrenal cortex- hormones and physiology Flashcards
Outline the differences in size, and function between the adrenal cortex and the medulla
Medulla = 10%
- Stress response
- Synthesises different hormones of similar chemical structure (catecholamines). Steroid hormones derived from dietary cholesterol
Cortex = 90%
- Stress, sodium and glucose homeostasis
- ESSENTIAL FOR LIFE
- Glucocorticoids and mineralcorticoids
Outline the 3 layers of the adrenal cortex. Why is this relevant?
Outer zona glomerulosa - contains 18-hydroxyase (synthesises aldosterone)
Middle zona fasciculata and Inner zona reticularis - both contain 17a- hydroxylase, hence 17a-hydroxypregnenolone, 17a-hydroxyprogesterone and the hormones derived from them
Cells in different layers have different enzymes and therefore synthesise different adrenocortical hormones
Comment of the androgen secretion from the adrenal cortex
Adrenal cortex secretes small quantities of androgens such as dehydroepiandrosterone, androsterodione, testosterone and oestrogens e.g. oestradiol
Only significant in adrenal disorders
Comment on the control of synthesis, secretion and actions of the mineralcorticoids and glucocorticoids
Controlled independently
Hypothalamus : CRH –> ant. Pituitary gland: ACTH –> Adrenal : (free) cortisol
Free cortisol inhibits CRH release from hypothalamus (negative feedback). Its inhibitory effects are FAST
Secretion of ACTH is pulsatile (peak in morning, nadir in middle of night)
-Increased secretion at time of prolonged stress
Cortisol secretion shows same patter but peak and nadir occur 2 hour post ACTH (pattern related to sleep/wake cycle; disrupted by shift work and long haul travel)
How are glucocorticoids transported?
Gestational changes?
Only 10% free cortisol in blood (active), the rest is bound to plasma proteins
- 75% Corticosteroid binding globuin -CBG
- 15% Albumin
**The same proteins transport the other glucocortocoids and progesterone
Pregnancy associated with increased CBG –> compensatory increase in circulatory [plasma cortisol]. Free cortisol remains stable
Where are adrenal steroids metabolised?
Mainly in liver where they are glucuronidated to form water soluble forms which can be secreted in urine
What does cortisol do at normal physiological concentrations?
IMPORTANT IN CARBOHYDRATE METABOLISM
- Antagonise effects on insulin on cellular uptake of glucose
- Stimulate glycogenolysis
- Stimulate hepatic gluconeogenesis
- Stimulates lipolysis and mobilisation of fatty acids partially by potentiating the effects of GH and the catecholamines.
What does cortisol do at excessive concentrations?
- Fat synthesis and deposition in novel anatomical sites (face, trunk and the intrascapular region of shoulders)
- Stimulate AA uptake in the liver causing increased gluconeogenesis
- Inhibits AA uptake and protein synthesis to leading to a net loss of skeletal protein
- Increases vasoconstictor responses to catecholamines –> increased BP
What is the effect of glucocorticoids on aldosterone receptors?
They can stimulate aldosterone receptors although aldosterone- sensitive tissues possess an enzyme - 11b-hydroxysteroid dehydrogenase1- which converts cortisol to inactive cortisone
- Cortisol stimulation of aldosterone receptors leads to psychological effects with possible feelings of elation or sedation
- Mineralocorticoid actions of glucocorticoids only apparent at high concentrations
Generally speaking whathappens in states of physiological or psychological stress?
(e.g. infection, trauma, hypoglycaemia)
Rapid secretion of ACTH and corticosteroids
As concentration increases, additional effects of these hormone become apparent
What happens in prolonged stress?
- Glucocorticoid maintain enhanced supply of glucose which may be required for the prolonged response to the stressor, but also suppresses inflammatory response (this potentiates adverse effects of injury and retards tissue repair)
In the absence of corticosteriods, mild stress could be fatal
What happens in injury?
- Pain alerts sufferer to damage
- Oedema dilutes any toxic substances that may be present and immobilises and stabilises joints
- Infiltration by leukocytes destroys any invading cells whilst antibodies inactivate foreign proteins
- Tissue repair increased by prostaglandins
How do glucocorticoids affect body’s defence systems?
- Suppresses lymphoid tissue, decreases antibody production and inhibits cellular immune system
- Stabilises leukocyte membranes and decreases release of proteolytic enzymes
- Inhibit phospholipase A2 and decreases synthesis of inflammatory mediators
Outline the adrenocortical stress response
Decreased inflammatory response
- Removes pain and decreases the immobilisation induced by the oedema
- Steroid-induced sedation also leads to lack of awareness of severity
** Overall the individual is able to perform despite injury/infection
How is the secretion of mineralcorticoids controlled?
Aldosterone and 11-deoxycorticosterone are the physiologically important mineralcorticoids
- Aldosterone secretion relatively uninfluenced by ACTH (but ATH stimulates the initial conversion of cholesterol to pregnenolone)
The major controlling factor in the secretion of aldosterone is the RAAS. Also directly stimulated by trauma, anxiety, hyperkalaemia and hyponatraemia
- Inhibited by atrial natriuretic peptide (ANP)
