Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
36 Cards in this Set
- Front
- Back
Hypothalamus to adrenal gland
|
CRH released by hypothalamus -->anterior pituitary -->ACTH(adrenocorticotropic hormone)-->acts on cells of the adrenal gland -->production of several steroid hormones |
|
Adrenal Gland
|
Two parts: 1. Adrenal cortex: steroid hormones 2. Adrenal medulla: epinephrine, norepinepherine |
|
Adrenal Cortex
|
1. Zona glomerulosa (aldosterone synthase) 2. Zona fasciculate 3. Zona reticularis 11B-hydroxylase 17a-hydroxulase (cortisol, androgens) |
|
Stimulation of Hypo-pitui-adreno- axis: 1
|
in response to a stimulus (e.g.stress) the hypothalamus releases CRH CRH binds receptors on the surfaceof endocrine cells of the anterior pituitary CRH induces the synthesis of proopiomelanocortin by the anterior pituitary |
|
Stimulation of Hypo-pitui-adreno- axis: 2
|
proopiomelanocortin is posttranslationally processed to adrenocorticotropic hormone (ACTH), among other biologically active peptides ACTH is released into bloodstream and binds receptors on the surface of endocrine cells of the adrenal cortex |
|
Stimulation of Hypo-pitui-adreno- axis: 3
|
the adrenal cortex secretes the steroid homones, aldosterone, cortisol, and androgens, from three distinct layers cortisol is a negative feedback inhibitor of CRH and ACTH secretion |
|
General process of steroid hormone synthesis occurs in cells of the adrenal cortex and gonads
|
ACTHbinds GPCR (receptor) on adrenal gland Stimulatesadenylyl cyclase (AC) Activatesprotein kinase A (PKA) Activatescholesterol esterase |
|
General process of steroid hormone synthesis occurs in cells of the adrenal cortex and gonads: Cholesterol Esterase
|
Cholesterol Esterase: -release free cholesterol from LDL in cytoplasm -Free Cholesterol is processed by enzyme in mitochondria and ER to form 5 different steroid hormones |
|
General process of steroid hormone synthesis occurs in cells of the adrenal cortex and gonads:
|
Newlysynthesized, lipophilic steroid hormones diffuse through the plasma membraneinto blood where they bind to carrier proteins (CBG and albumin) |
|
General process of steroid hormone synthesis occurs in cells of the adrenal cortex and gonads
|
-rate limiting step is conversion of cholesterol to pregnenolone
|
|
Glucocorticoids
|
-Glucocorticoidsregulate glucose metabolism; -Overall function to cope with environmental adversity: maintain carbohydrates stores prevent hypoglycemia |
|
mineralocorticoids
|
regulatesalt balance through the kidneys’ handling of Na+ and K+ |
|
Glucocorticoids: liver |
-increase gluconeogenesis by increasing activity and amount of enzymes |
|
Glucocorticoids in adipose |
-decrease glucose utilization -decrease insulin sensitivity -send glycerol to liver |
|
Glucocorticoids in muscle |
-increase muscle degradation (More AA to the liver) -decrease protein synthesis -decrease insulin sensitivity (saves glucose for nerve tissue to keep going) |
|
Synthetic modification of cortisol
|
-extra 1:2 double bond: increase glucocorticoid activity -methyl at c6 and c16: increase in glucocorticoid activity fluorine at c9: has mineralocorticoid function (fludrocortisone) |
|
Steroid hormones exert actions on target cells by binding cytosolic receptors |
-corticoisteroids are lipophilic -->go through PM of target cell. -bind receptors in the cytosol of target cells -ligand activated steroid hormone receptor form dimers -this result in enhancement or inhibition of gene transcription |
|
Pharmacological treatment of adrenocortical insufficiency (hormone replacement)
|
|
|
Types of adrenocortical insufficiency conditions
|
1. Primary adrenocortical insufficiency (Addison's disease) 3. Tertiary adrenocortical insufficiency |
|
Primary adrenocortical insufficiency (Addison's disease)
|
hyposecretion of glucocorticoids andmineralocorticoids due to adrenal cortex dysfunction; treated withhydrocortisone (identical to cortisol) and fludrocortisone (potent syntheticmineralocorticoid) |
|
Secondary adrenocortical insufficiency
|
hyposecretion of glucocorticoids due todeficiency of ACTH (pituitary dysfunction); treated with hydrocortisone onlybecause aldosterone secretion is maintained by angiotensin II |
|
Tertiary adrenocortical insufficiency
|
hyposecretion of glucocorticoids due todeficiency of CRH (hypothalamic dysfunction); treated with hydrocortisone onlybecause aldosterone secretion is maintained by angiotensin II |
|
Treatment of
congenitaladrenal hyperplasia |
- a group of diseases resulting from an enzyme defect in the synthesis of one or more of the adrenal hormones -treatment requires administration of sufficient corticosteroids to restore negative feedback of CRH and ACTH -choice of replacement hormone depends on the specific enzyme defect |
|
The adrenal-immune axis: anti-inflammatory effects of corticosteroids
|
-It decreases peripheral lymphocyte and macrophage activation -indirect inhibition of arachidonic acid synthesis, leading to decreased production of prostaglandins and leukotrienes |
|
Pharmacological treatment of inflammatory diseases
|
-Rheumatoid arthritis, Osteoarthritis, allergies (IM, IV) -Inflammatory skin conditions (topical) |
|
Pharmacological treatment of inflammatory diseases (structure of inhaled corticosteroids)
|
-highly potent glucocorticoids with little mineralocorticoid activity -high potency allows effective inhibition of local inflammation in respiratory tract most have almost complete first pass metabolism in liver ensuring that the inadvertatnly swallowed portion of the dose (80%) becomes inactivated |
|
Structure of synthetic corticosteroids
|
-prednisolone, methylprednisone, dexamethasone, fludrocortisone (known as 11-hydroxy glucocorticoids, physiologically active) |
|
Structure of synthetic corticosteroids
|
Prednisone, cortisone <-- 11-keto congeners prodrugs that require activation by 11B-hydroxysteroid dehydrogenase -cannot be used to treat inflammation of skin |
|
Osteoporosis
|
-glucocorticoids directly inhibit calcium uptake in the intestines -glucocorticoids inhibit the actions and formation of the biologically active form of vitamin D3 |
|
Osteoporosis
|
glucocorticoids decrease sex hormone synthesis (negative feedback) leading to decreased estrogen) |
|
Osteoporosis
|
|
|
Osteoporosis
|
if you have more osteoclasts than osteoblasts --> bone mass loss |
|
Treatment of Osteoporosis
|
-Bisphosphonic acid |
|
Treatment of Osteoporosis
|
alkalinephophatase, secreted by osteoblasts, cleavespyrophosphate to increase local phosphate concentrations which promotesmineralization (etidronate, risedronate, alendronate, ibandronate, amidronate, tiludronate,, zolendronic acid) --are analogs of pyrophosphate - they accumulate in bone and are incorporated into mineral matrix as bone is remodelled, bisphosphonates are released from the matrix and taken up (phagocytosis) by osteoclasts Within osteoclasts, bisphosphonates inhibit an important cholesteron biosynthetic pathway, resulting in osteoclast apoptosis |
|
Treatment of Osteoporosis: Selective Estrogen Receptor Modulators (SERMs)
|
SERM-ER complexes appear to bind selectively to tissue specific hormone response elements of DNA SERM-ER complexes may also recruit transcriptional co-repressors and co-activators in a tissue selective manner the SERM, raloxifene, is an ER agonist in bone, but an ER antagonist in endometrium and breast |
|
Pharmacological treatment of Osteoporosis (RANKL monoclonal antibody)
|
-in 2010 Canada approved Denosumab, a human monoclonal antibody against RANKL, for treatment of osteoporosis.
|