Pharmacology 3620 Lecture Notes - Lecture 39: Zona Fasciculata, Zona Glomerulosa, Adenylyl Cyclase
1 May 2018
School
Department
Course
Professor
13. Drugs used in Inflammatory Diseases and Osteoporosis
Learning Objectives
● Recall the mechanism of action of steroid hormones.
● Identify the major effects of glucocorticoids on human physiology.
● Explain why glucocorticoids are effective in treating inflammatory conditions.
● Identify the groups of synthetic modifications to the cortisol backbone that make it
suitable for various corticosteroid anti-inflammatory therapies.
● Identify the most common adverse effect of long term corticosteroid therapy, and
integrate this effect with the known effects glucocorticoids on human physiology.
● Recall the definition of osteoporosis, and the bone pathophysiology associated with this
disease.
● Identify three major classes of drugs used to treat osteoporosis, and explain their
mechanisms of action
Adrenal Gland
● Adrenal Cortex
○ Secrete steroid homes
○ 3 morphologically distinct layer
■ Zona glomerulosa
● Aldosterone production
■ Zona fasciculata
● Cortisol and androgen production
■ Zona reticularis
● Cortisol and androgen production
● Adrenal Medulla
○ Norepinephrine
○ Epinephrine
Stimulation of the HPA axis results in the secretion of steroid hormones
● CHR is released from the hypothalamus in response to stress
● CHR binds to the anterior pituitary
○ Induce the synthesis of proopiomelanocortin
○ proopiomelanocortin is processed to become ACTH
● ACTH is released into the bloodstream and binds to endocrine cells of the adrenal cortex
● Adrenal cortex secretes aldosterone, cortisol and androgens
● Cortisol is the negative feedback inhibitor of CRH and ACTH
Steroid Hormone Production
● ACTH binds to its receptor
○ Induce a GPCR signaling cascade
■ Get activation of adenylyl cyclase and PKA
○ PKA activates cholesterol esterase
● Cholesterol esterase free up cholesterol from lipid droplets within the cytoplasm
find more resources at oneclass.com
find more resources at oneclass.com
● STAR (steroidogenic acute regulatory protein)
○ Delivers the free cholesterol to the inner mitochondrial membrane
■ Where CYP11A is
● In the mitochondria and smooth ER, enzymatic process generates 5 different steroid
hormones from the cholesterol
● Steroid hormone then diffuse out of the cell and into blood
○ Binds to carrier proteins (binding globulins and albumin) for transport in the blood
The adrenal cortex secretes five steroid hormones synthesized from cholesterol
● Rate limiting step:
○ CYP11A
■ Converts cholesterol to pregonsion
● Produces
○ Glucocorticoids
■ Cortisols
■ Regulate glucose metabolism
○ Mineralocorticoids
■ Corticosterone
■ Aldosterone
■ Maintain salt balance through the kidney
● Na+ and K+
○ Sex steroids
■ Dehydroepiandrosterone
■ Androstenedione
● Steroid hormones diffuse through the plasma membrane and bind receptors IN the
cytosol of target cells
○ Ligand activate steroid hormone receptors form dimers
○ Dimers travel to the nucleus to bind to steroid hormone response elements in the
DNA
○ Get gene transcription (enhancement or inhibition)
Major actions of glucocorticoids (cortisol)
● Binds glucocorticoid receptors to alter gene transcription in multiple tissues
● Promotes the maintenances of carbohydrates stores and the circulating levels of glucose
○ So that tissue can use it in times of stress
● In muscle tissue:
○ Increase protein degradation, decrease protein synthesis
○ Decrease glucose utilization
○ Decrease sensitivity to insulin
● In liver tissue:
○ Increase glycogen storage and gluconeogenesis
■ More gluconeogenesis than glycogen storage
○ Increase activity and amount of enzymes
● In adipose cells:
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Drugs used in inflammatory diseases and osteoporosis. Identify the major effects of glucocorticoids on human physiology. Recall the mechanism of action of steroid hormones. Explain why glucocorticoids are effective in treating inflammatory conditions. Identify the groups of synthetic modifications to the cortisol backbone that make it suitable for various corticosteroid anti-inflammatory therapies. Identify the most common adverse effect of long term corticosteroid therapy, and integrate this effect with the known effects glucocorticoids on human physiology. Recall the definition of osteoporosis, and the bone pathophysiology associated with this disease. Identify three major classes of drugs used to treat osteoporosis, and explain their mechanisms of action. Stimulation of the hpa axis results in the secretion of steroid hormones. Chr is released from the hypothalamus in response to stress. Acth is released into the bloodstream and binds to endocrine cells of the adrenal cortex. Adrenal cortex secretes aldosterone, cortisol and androgens. Cortisol is the negative feedback inhibitor of crh and acth.
