Adrenal DSA Flashcards
- Describe the pathways that control steroid hormone production including a description of the enzymes 17α-hydroxylase, 21-hydroxylase, and 11β-hydroxylase.
cortisol- synthesized n the zonae fasciculata/reticularis, which contains all of the enzymes required to convert cholesterol to cortisol:
cholesterol desmolase, which converts cholesterol to pregnenolone;
17α-hydroxylase, which hydroxylates pregnenolone to form 17-hydroxypregnenolone;
3β-hydroxysteroid dehydrogenase, which converts 17-hydroxypregnenolone to 17-hydroxyprogesterone;
and 21β-hydroxylase and 11β-hydroxylase, which hydroxylate at C11 and C21 to produce the final product, cortisol
Adrenal androgens (DHEA and androstenedione). – The precursors for the adrenal androgens are 17-hydroxypregnenolone and 17-hydroxyprogesterone, which are converted to androgens by removal of the C20,21 side chain.
The major mineralocorticoid in the body is aldosterone, which is synthesized only in the zona glomerulosa. The steps required to convert cholesterol to corticosterone are identical to those in the zona fasciculata, and the addition of aldosterone synthase in the zona glomerulosa converts corticosterone to aldosterone.
- Describe the actions of catecholamines in the body (i.e. which receptors do catecholamines act on and what is the effect).
Catecholamines cause general physiological changes that prepare the body for physical activity (fight-or-flight response). Some typical effects are increases in heart rate, blood pressure, blood glucose levels, and a general reaction of the sympathetic nervous system.
The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline).
- List the steroid hormones produced by the adrenal cortex and know in which layer the hormones are produced.
– Outer- zona glomerulosa produces mineralocorticoid aldosterone
– Middle- zona fasciculata produces the glucocorticoid cortisol
– Inner- zona reticularis produces androgens
- Describe the actions of mineralocorticoids, corticosteroids, and androgens.
Mineralocorticoids: Briefly, aldosterone has three actions on the late distal tubule and collecting ducts of the kidney: It increases Na + reabsorption, it increases K + secretion, and it increases H + secretion. Its effects on Na + reabsorption and K + secretion are on the principal cells, and its effect on H + secretion is on the α-intercalated cells. Thus, when aldosterone levels are increased (e.g., due to an aldosterone-secreting tumor), Na + reabsorption, K + secretion, and H + secretion all are increased.
Glucocorticoids: are essential for life. If the adrenal cortex is removed or is not functioning, exogenous glucocorticoids must be administered or death will ensue. The actions of glucocorticoids (e.g., cortisol) are essential for gluconeogenesis, vascular responsiveness to catecholamines, suppression of inflammatory and immune responses, and modulation of CNS function.
Androgens: The adrenal cortex produces the androgenic compounds, DHEA and androstenedione, which are converted to testosterone primarily in the testes. In males, adrenal androgens play only a minor role because de novo synthesis of testosterone from cholesterol in the testes is much greater than testosterone synthesis from adrenal androgenic precursors. In females, however, adrenal androgens are the major androgens, and they are responsible for the development of pubic and axillary hair and for libido.
- Describe the regulation mechanism for aldosterone and cortisol synthesis.
the synthesis and secretion of steroid hormones by the adrenal cortex depend on the stimulation of cholesterol desmolase (the first step) by ACTH. In the absence of ACTH, biosynthesis of adrenocortical steroid hormones ceases. Two questions arise, therefore: What regulates the secretion of ACTH? What special regulatory factors control the functions of the zonae reticularis, fasciculata, and glomerulosa?
♦ The zonae fasciculata/reticularis, which secrete glucocorticoids and androgens, is under the exclusive control of the hypothalamic-pituitary axis. The hypothalamic hormone is corticotropin-releasing hormone (CRH), and the anterior pituitary hormone is ACTH.
♦ The zona glomerulosa, which secretes mineralocorticoids, depends on ACTH for the first step in steroid biosynthesis, but otherwise it is controlled separately via the renin-angiotensin-aldosterone system.
Actions of cortisol
- Increases gluconeogenesis, protein catabolism, lipolysis, and decreases glucose utilization and insulin sensitivity
- Anti-inflammatory effects
• Inhibits phospholipase A2
• Inhibits histamine and serotonin release - Suppresses immune responses
• T cell suppression (IL-2)
• Lyses eosinophils - Maintain vascular responsiveness to catecholamines
• Maintains normal blood pressure
• ↓ cortisol → hypotension - Inhibition of bone formation
• Decreases type I collagen
• Decreases osteoblast activity
• Decreases gut Ca2+ absorption - Increases glomerular filtration rate (GFR)
• Causes vasodilation of afferent arterioles - Decreases REM sleep (psychosis)
• Also increases wake time
The precursor for all adrenocortical steriods is
cholesterol
The enzymes catalyzing the conversion of cholesterol to active steroid hormones require
cytochrome P450, oxygen, and NADPH
Regulation of secretion of adrenocorical steroids
♦ The zonae fasciculata/reticularis, which secrete glucocorticoids and androgens, is under the exclusive control of the hypothalamic-pituitary axis. The hypothalamic hormone is corticotropin-releasing hormone (CRH), and the anterior pituitary hormone is ACTH.
♦ The zona glomerulosa, which secretes mineralocorticoids, depends on ACTH for the first step in steroid biosynthesis, but otherwise it is controlled separately via the renin-angiotensin-aldosterone system.
the affinity of mineralocorticoid receptors for cortisol is, surprisingly, just as high as their affinity for aldosterone. Because circulating levels of cortisol are much higher than circulating levels of aldosterone, it seems that cortisol would overwhelm and dominate the mineralocorticoid receptors. How would the kidneys know that a change in aldosterone concentration had occurred and that mineralocorticoid actions are desired?
The “problem” is solved by the renal cells themselves. They contain the enzyme 11β-hydroxysteroid dehydrogenase, which converts cortisol to cortisone; in contrast to cortisol, cortisone has a low affinity for mineralocorticoid receptors. In this way, cortisol is effectively inactivated in mineralocorticoid target tissues. This unique solution allows changes in blood levels of aldosterone to be “seen” by the renal cells and not be overshadowed by the high circulating levels of cortisol. This inactivation of cortisol in mineralocorticoid target tissues also explains why, when circulating levels of cortisol are high, the cortisol has only weak mineralocorticoid activity (despite its high affinity for mineralocorticoid receptors).
