Physiology 2130 Lecture Notes - Lecture 60: Zona Fasciculata, Zona Glomerulosa, Zona Reticularis
1 May 2018
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Lecture 060: Adrenal Physiology
Functional anatomy
● Adrenal cortex
○ Source of adrenal steroids
○ 3 zones
■ Zona glomerulosa
● Makes aldosterone
■ Zona fasciculata
● Makes cortisol
■ Zona reticularis
● Makes sex steroids
● Adrenal medulla
○ Composed of “chromaffin” cells
■ Secretes catecholamines
■ Controlled by direct innervation ((neuroendocrine response)
Adrenal Steroidogenesis
● Occurs in the adrenal gland
● Precursor is cholesterol
● Intracellular enzymes in the adrenal gland convert cholesterol into different
hormones
○ Steroidogenic enzymes are cytochrome p450s (e.g. CYP17)
○ Found in the membrane of mitochondria and the ER
○ Energy comes from the ETC
HPA Axis
● In response to systemic/chronic stress (cold, hypoglycemia, fear)
○ Hypothalamus release corticotropin releasing hormone (CRH)
■ Acts on the ACTH receptor in anterior pituitary
○ Anterior pituitary release ACTH
■ Acts on the ACTH receptors adrenal cortex
○ Adrenal cortex release cortisol
■ Cortisol increase blood glucose
● Gluconeogenesis
● Muscle catabolism (amino acid)
● Inhibition of GLUT4 activity
■ High levels of cortisol negative feedback on the hypothalamus and
anterior pituitary to stop production of CRH and ACTH
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Production of Cortisol
● ACTH binds to its GPCR on the adrenal gland causes:
1. Increase activity of adenylyl cyclase and level of cAMP
■ Increase the activity of cholesterol ester hydrolase (CEH)
2. Upregulates the expression of the ACTH receptor itself
■ Amplifies the action of the feedforward loop
● Increased action, makes more cortisol
3. Upregulates steroid acute regulatory protein (StAR) activity
■ Mobilizes cholesterol into the mitochondria
4. Upregulate the receptor for LDL
■ LDL is a precursor for cholesterol
● cAMP activate cholesterol ester hydrolase
○ Librates cholesterol by removing the ester from cholesterol ester
● Cholesterol is brought into the mitochondria by StAR
○ RATE LIMITING STEP
● Cholesterol is converted into cortisol on the mitochondrial membrane
ACTH Receptor
● Is a GPCR coupled to cAMP
● Promotes the activity of CEH
● Rapidly increase the production of StAT
○ Movement of Cholesterol into the mitochondria is the rate-limiting
step in steroidogenesis
● Expressed primary in the zona reticularis and zona fasciculata
○ Can get some aldosterone secretion
Cortisol
● Is a steroid hormone
○ Not soluble
● 75% in plasma is bound to corticosteroid binding globulin (CBG)/transcortin
● 15% bound to human serum albumin (HSA)
● 10% “free” available for biological activity
○ Carrier protein will dissociated when cortisol reaches its target tissue
■ Cortisol will dissolve easily across the membrane
● Primarily metabolized in the liver
● Excreted by the kidney
○ Can use urine tests for steroid abuse
■ look for the sulfated form of cortisol
ACTH and Cortisol release is pulsatile
● Diurnal rhythm
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find more resources at oneclass.com
Document Summary
Intracellular enzymes in the adrenal gland convert cholesterol into different hormones. Steroidogenic enzymes are cytochrome p450s (e. g. cyp17) Found in the membrane of mitochondria and the er. In response to systemic/chronic stress (cold, hypoglycemia, fear) Acts on the acth receptor in anterior pituitary. Acts on the acth receptors adrenal cortex. High levels of cortisol negative feedback on the hypothalamus and anterior pituitary to stop production of crh and acth. Acth binds to its gpcr on the adrenal gland causes: increase activity of adenylyl cyclase and level of camp. Increase the activity of cholesterol ester hydrolase (ceh: upregulates the expression of the acth receptor itself. Amplifies the action of the feedforward loop. Increased action, makes more cortisol: upregulates steroid acute regulatory protein (star) activity. Mobilizes cholesterol into the mitochondria: upregulate the receptor for ldl. Librates cholesterol by removing the ester from cholesterol ester. Cholesterol is brought into the mitochondria by star. Cholesterol is converted into cortisol on the mitochondrial membrane.
