Lecture 16: Corticosteroids Flashcards
Adrenal Gland secretion
-corticoids
-androgens
-epi and NE
Adrenocorticoids
-glucocorticoids
-mineralocorticoids
Glucocorticoids
-stress hormones
-inc circulating glucose
-potent anti-inflammatory efects
-cortisol
Mineralcorticoids
-Na+ retention
-inc BV
-inc BP
-aldosterone
Epinephrine mode of action
-binds B-receptor (GPCR)
-initiate signal transduction cascade
-induce immediate response
-break down glycogen
-release glucose
Cortisol (hydrocortisone) mode of action
-binds to glucocorticoid receptor (nuclear)
-regulate gene transcription/translation/protein production
-induces long term response
-induces gluconeogenic enzymes
-inhibit inflammatory processes
CRH
-corticotropin releasing hormone
-induced by stress
-inhibited by cortisol feedback
ACTH
-adrenocorticotropic hormone
-induced by stress and CRH
-inhibited by cortisol feedback
Mineralcorticoid synthesis
-not by the anterior pituitary!
-renin-angiotensin-aldosterone system
renin-angiotensin-aldosterone system
-liver to angiotensinogen to angiotensin I (renin)
-I to II (ACE)
-II to aldosterone in adrenal glands
Glucocorticoid Responsive Elements (GRE)
-specific DNA seq where DNA-binding domain of activated dimers
-alter rate of transcription
Enzymes upregulated by glucocorticoids
-PEP carboxykinase
-lipocotrin I
-enzymes for gluconeogenesis and anti-inflammatory proteins
PEP carboxykinase
-catalyzes rate-limiting step in gluconeogenesis
-upregulated by glucocorticoids
Lipocortin I
-suppress phospholipase A2 which has a critical role in eicosanoid synthesis
-upregulated by glucocorticoids
Mech of immunosuppression by glucocorticoids
-activated glucocorticoid receptor (GR) binds NFkB
-prevents NFkB binding to its response element
-repress cytokine genes
Physiological effects of glucocorticoids
-inc blood glucose levels
-immunosuppression
Physiological effect of glucocorticoid on liver
-inc gluconeogenesis
-inc glycogen storage
physiological effect of glucocorticoid on muscle
-promote protein degradation
-dec protein synthesis
-dec sensitivity to insulin
physiological effect of glucocorticoids on adipose tissue
-promote lipolysis
-dec sensitivity to insulin
Physiologic effect of glucocorticoids on the immune system
-block cytokine synthesis (immunosuppression)
-block eicosanoid synthesis (anti-inflammation)
Adrenal insufficiency
-HYPOadrenalism
-decreased secretion of steroid hormones by adrenal cortex
Adrenal insufficiency causes
-primary: destruction of cortex by TB or atrophy (addison’s disease)
-secondary: dec secretion of ACTH due to disease of anterior pituitary
Adrenal insufficiency symptoms
-weakness
-anorexia/anemia/nausea
-depression
Primary adrenal insufficiency
-destruction of cortex by TB or atrophy
-addison’s disease
-Low BP and hyperpigmentation of skin as additional symptoms
Cessation of long-term systemic glucocorticoid therapy can lead to
Addisonian symptoms
Primary adrenal insufficiency effect (adrenal defect)
-inc CRH
-inc ACTH
-dec Cortisol
-dec Aldosterone
Secondary adrenal insufficiency effect (pituitary defect)
-inc CRH
-dec ACTH
-dec Cortisol
-aldosterone unaffected
Tertiary adrenal insufficiency effect (hypothalmic defect)
-dec CRH, ACTH, Cortisol
-no effect on aldosterone
Cushing’s disease
-HYPERadrenalism
-adrenal, pituitary, or ectopic
Causes of Cushing’s disease
-tumors in adrenal cortex
-inc ACTH production due to pituitary carcinoma
-ectopic production of ACTH bc non-pituitary carcinoma
Symptoms of Cushing’s disease
-inc protein catabolism (bruising/wasting)
-inc glucose levels
-osteoporosis
-opportunistic infections
Long-term therapeutic use of systemic glucocorticoids can lead to
Cushing’s symptoms
Adrenal Cushing’s effect
-dec CRH
-dec ACTH
-inc Cortisol
Pituitary Cushing’s effect
-dec CRH
-inc ACTH
-inc Cortisol
Ectopic Cushing’s effect
-dec CRH
-dec ACTH
-inc ectopic ACTH
-inc Cortisol
