Corticosteroids Flashcards
Four main classes of steroids?
- sex hormones
- bile acids
- vitamins
- adrenocorticoids
Where are adrenocorticoids formed?
in the adrenal cortex
what do mineralocorticoid affect?
sodium and water retention
What do glucocorticoids affect?
- glucose homeostasis
- and have anti-inflammatory activity
how many rings in a steroid structure?
4 (A,B,C,D)
what conformation are rings A,B and C of the glucocorticoid structure?
a chair conformation
what are the ring junctions in a glucocorticoid structure?
trans (meaning hydrogens at ring junction are on opposite sides)
how do glucocorticoids bind to receptors?
via the beta face
what is the structure of the glucocorticoid?
- at least one double bond in A-ring
- has an OH at C-11, C-17 and C-21
- has a ketone group at C-3 and C-20
what is the starting material for steroid hormone synthesis?
cholesterol
What two major classes of adrenocorticoids are released from the adrenal cortex into the circulatory system?
- hydrocortisone
2. aldosterone
Explain the feedback mechanism for the maintenance of adrenocorticoid levels?
- adrenocorticoid levels low.
- hypothalamus secretes corticotrophin-releasing factor (CRF) to the pituitary.
- Adrenocorticotrophic hormone (ACTH) released from anterior pituitary
- this stimulates adrenal cortex to release adrenocorticoids
- adrenocorticoid levels become high
- CRF secretion from hypothalamus is inhibited
What are the pharmacological activities of glucocorticoids?
- anti-inflammation
- inhibit cytokines
- inhibit mast cell release of autocoids
where do steroids and drugs that mimic glucocorticoids act?
on gene’s
Explain the gene activity of glucocorticoids?
- steroid hormones enter cell by diffusion, as it’s lipophilic
- they then combine with intracellular receptors (receptors are inactive and located in the cytoplasm)
- this causes a conformational change exposing a DNA binding domain
- receptor-steroid complex move to the nucleus and bind to steroid response elements in DNA
- specific gene transcription is either switched on or off to alter mRNA levels and the rate of synthesis of mediator proteins
How do glucocorticoids work as anti-inflammatory drugs?
- affect protein synthesis hence increasing lipocortin
- lipocortin inhibits phospholipase A2 hence cell membrane phospholipids can’t be converted to arachidonic acid, then no prostaglandin and thromboxane formation.
- they cause the infiltration of eosinophils and activate CysLT receptors and bronchoconstriction.