Lecture 16- Hormones Of The Adrenal Cortex Flashcards
Hormones of the adrenal gland
Adrenal gland consists of = cortex + medulla
Adrenal medulla = secretes adrenaline
Adrenal cortex = secretes steroid hormones
Glucocorticoids= produced by the middle zona fasciculata. Responsible for= normal metabolism + resistance to stress. E.g. hydrocortisone (cortisol)
Mineralcorticoids= produced by the outer zona glomerulosa. Responsible for= regulating salt + water metabolism. E.g. aldosterone
Inner zona reticularis of the adrenal cortex = secretes adrenal androgens = dehydroepiandrosterone (DHEA)
Hormones of the adrenal cortex
Natural glucocorticoid= hydrocortisone (cortisol)
Synthetic glucocorticoids= cortisone, prednisolone, prednisone, dexamethasone + bethamethasone
Mineralocorticoids= aldosterone, deoxycorticosterone (DOC), fludrocortisone (synthetic)
Synthesis and release of glucocorticoids
Synthesised + released as required under the influence of circulating ACTH secreted from the anterior pituitary
ACTH secretion is positively regulated by CRF released from the hypothalamus + negatively by blood glucocorticoids
Glucocorticoids= present in the blood
Healthy humans= well-defined circadian rhythm in the secretion with the blood conc being highest in morning, gradually diminishing throughout the day + reaching a low point in evening/night
Mechanisms of action of glucocorticoids
Glucocorticoid effects = initiated by their interaction with specific intracellular glucocorticoid receptors belonging to the nuclear receptor superfamily
Receptors = regulate the transcription of target genes
Ligand-bound receptor complex = actively transported into the nucleus -> interacts with DNA + nuclear points
Pharmacological actions of glucocorticoids; Metabolic Effects
Main metabolic effects = on carbohydrate + protein metabolism - same effects are responsible for some of the serious adverse effects associated with their use in therapeutic doses
Fasting state- Gcoids cause both a decrease in the uptake + utilisation of glucose and an increase in gluconeogenesis = resulting in a tendency to hyperglycaemia
= ^ decreased protein synthesis + increased protein breaks down, particularly in muscle -> wasting
Gcoids= stimulate lipolysis to supply glucose
Large doses of Gcoids = given over a long period = redistribution of body fat characteristics of Cushing’s syndrome
Pharmacological actions of glucocorticoids;
Anti-inflammatory + immunosuppressive effects
When given therapeutically = Gcoids have anti-inflammatory + immunosuppressive effects - mainly due to their effects on peripheral leukocytes
Clinically = suppress graft rejection, Gcoids suppress the initiation + generation of an immune response mounted against the new ‘invader’
Inhibit birth the early + late (chronic) manifestations of inflammation
Pharmacological actions of glucocorticoids;
Anti-inflammatory + immunosuppressive effects
Gcoids suppress the effects of inflammatory cytokines + chemokines and inhibit the functions of tissue macrophages
Influence the inflammatory response by reducing the prostaglandins and leukotrienes = resulting from the activation of phospholipase A2
Anti-inflammatory + immunosuppressive effects of Gcoids = useful therapeutically but are also responsible for some of their most serious adverse effects
Pharmacological actions of glucocorticoids; Resistance to stress
By raising plasma glucose levels= Gcoids provide the body with the energy it requires to combat stress caused by trauma, flight, infection, bleeding or debilitating disease
Unwanted effects of glucocorticoids
Major unwanted effects of Gcoids = results of their hormonal actions -> clinical picture of the drug-induced Cushing’s syndrome
- likely to occur with large doses/prolonged administration rather than replacement therapy
Possible unwanted effects= suppression of the response to infection/injury, wound healing may be impaired + peptic ulceration may occur
Drugs= used in anti-inflammatory + immunosuppressive therapy= metabolic actions = unwanted side effects
Tendency to hyperglycaemia that occurs with exogenous Gcoids = may develop into actual diabetes
Osteoporosis = with the attendant hazard of fractures= main limitation to long-term Gcoid therapy
Adrenal suppression; sudden withdrawal of the drugs after prolonged therapy= acute adrenal insufficiency
Therapeutic uses of glucocorticoids
Replacement therapy for adrenocortical insufficiency (Addison’s Disease) = caused by adrenal cortex dysfunction
Relief of inflammatory symptoms;
* in asthma
* topically in various inflammatory conditions of skin, eye, ear/ nose (e.g. eczema, allergic conjunctivitis/rhinitis)
* hypersensitivity states (e.g. severe allergic reactions)
* diseases with autoimmune/inflammatory components (e.g. RA/ connective tissue diseases + IBD)
* prevent graft-versus-host disease following organ/bone marrow transplantation
Acceleration of lung maturation in respiratory distress syndrome (foetal cortisol is a regulator of lung maturation)
