Adrenal Gland 1 Flashcards
What part of the adrenal gland secretes catecholamines?
Adrenal medulla located in the cetner of the adrenal gland
What are the three zones of the adrenal cortex and what do they synthesize?
Zona glomerulosa - outer
Zona fasciculata - middle
Zona reticularis- inner
All three zones produce both pregnenolone and progersterone
Where does the conversion of cholesterol to 11-deoxycorticosterone (DOC) occur?
Zona glomerulosa and Zona fasciculata
What zone synthesizes aldosterone?
Zona glomerulosa
Only zone that expresses aldosterone synthase that converts DOC to aldosterone
What is the functions of 11B-hydroxylase?
Converts DOC to corticosterone (cortisol) in the zona fasciculata
What is enzyme P450c17?
Enzyme required for the synthesis of cortisol and androgen synthesis
Has 17a-hydroxylase and 17,20-lyase activities
Expressed in both the zona fasciculata and zona reticularis
Where are glucocorticoids mainly synthesized?
Zona fasciculata with small amounts in the zona reticularis
Zona glomerulosa lacks 17a-hydroxylase activity so it is unable to synthesize cortisol and androgens
Where are androgens mainly synthesized?
Zona reticularis
How is transcription of StAR induced in the zona fasciculata and reticularis?
ACTH via a cAMP-dependent mechanism
How is transcription of StAR induced in the zona glomerulosa?
Angiotensin II via Ca-calmodulin-dependent mechanism
What is the effect off K on aldosterone synthesis?
K induces aldosterone synthesis in the zona glomerulosa via activation of VG-Ca channels
What is the primary action of mineralcorticoids?
Maintain ECF volume by regulating Na reabsorption
Also promote K and H excretion
Principal mineralcorticoid is aldosterone
What adrenal steroids have mineralcorticoid activity?
DOC and Cortisol
Aldosterone is quantitatively more important than DOC because of its large free fraction (40-50% compared to 5%)
Cortisol contributes very little to mineralcorticoid activity
Why doesn’t cortisol contribute to mineralcorticoid activity?
It is converted to cortisone by 11B-HSD2
This enzyme is expressed in tissues with glucocorticoid receptors
Cortisol can cause hypertension if this enzyme is inhibited
What is the principal adrenal androgen released by the zona reticularis?
Dehydroepiandrosterone (DHEA)
Secreted as DHEA sulfate (DHEAS)
High affinity for albumin
Small amounts of androstenedione are also released
Why do DHEA and androstenedione have little androgen activity?
Low affinity for the androgen receptor
They are converted to more potent androgens peripherally
Describe androgen production during pregnancy?
Fetal adrenal gland produces large amounts of DHEA sulfate, which is converted to estrogen by the placenta
What layers is the fetal adrenal cortex composed of?
Neocortex
Fetal zone - source of DHEAS
What is adrenarche?
Increase in circulating levels of adrenal androgens starting at 6-7 in girls and 7-8 in boys and continue to increase progressively through adolesence
Not invovled in the initiation of puberty
What is the relationship between ACTH and adrenal androgens?
ACTH plays a role in regulating adrenal androgen secretion, but it is not the only factor
Adrenal androgens do not exert a negative feedback on ACTH secretion
What is the state of circulating cortisol?
5-10% of circulating cortisol is free
75% bound to Corticosteroid binding globulin (CBG)
15% bound to albumin
What is the most accurate measurement of daily cortisol output?
24-hour urinary excretion of unmetabolized cortisol
Why do synthetic glucocorticoids have enhanced activity?
Increased receptor affinity
Delayed plasma clearance
What is the principal physiological regulator of cortisol release?
ACTH
Released in secretory pulses throughout the day
What are the acute actions of ACTH?
Increase hydrolysis of cholesterol esters
Synthesis of StAR
Increased blood flow to the adrenal cortex
What are the chronic effects of ACTH?
Increase in growth and cell proliferation in the Zona reticularis and fasciculata
Increased synthesis of steroidogenic enzymes, LDL receptors
What results from long-term suppression of ACTH?
Adrenal gland atrophy
Conversely, excessive ACTH production will cause adrenal gland hypertrophy
How is ACTH release controlled?
CRH is the principal regulator of ACTH secretion
What is the circadian pattern of cortisol release?
Diurnal rhythm
Cortisol levels are highest in the morning upon awakening
How does stress affect cortisol?
Stress increases cortisol release via the CNS
CNS increases the activity of CRH-secreting hypothalamic neurons
Also causes the release of vasopressin that potentiates CRH-mediated ACTH secretion
Strong, overrides negative feedback control
What is the negative feedback loop for cortisol?
Cortisol exerts a negative feedback effect on the hypothalamus and pituitary
What is the permissive effect of cortisol?
Doesn’t initiate processes specifically, but rather ensures the cell has the capacity to fully respond to stimuli by regulating the expression of certain genes for a particular process
E.g. maintains glycogen synthase, therefore has a permissive effect on glucagon- and epinephrine-induced glycogenolysis
How does cortisol protect against hypoglycemia?
Promotes gluconeogenesis via pathway enzyme production
Mobilizes amino acids for use in gluconeogenesis
Permissive effect on glycogenolysis
What is the effect of cortisol on fat metabolism?
When present, promotes fat deposition in the trunk and face
Permissive effect on enzymes necessary to support fat mobilization
What are the metabolic effects experienced by hypo- and hyperadrenal patients?
Hypoadrenal - fasting hypoglycemia
Glucocorticoid excess- hyperglycemic and hyperinsulinemic
What are the cardiovascular effects of cortisol?
Required for normal responsiveness of blood vessels to vasoconstrictors
Stimulates erythropoietin
What are the nervous system effects of cortisol?
Mood, behavior, wakefulness and the perception of sensory signal intensity
What are the developmental effects of glucocorticoids?
Alveolar maturation and surfactant production
What are the effects of cortisol on calcium homeostasis?
Excess levels of glucocorticoids increases risk for osteoporosis
Antagonize the effects of Vitamin D
Inhibit renal Ca reabsorption
Inhibits bone formation
What are the anti-inflammatory actions of glucocorticoids?
Suppress the inflammatory response by blocking the expression of genes that code for pro-inflammatory cytokines
Inhibit enzymes like phospholipase A2 and NO synthase
Induces synthesis of Lipocortin (inhiibts PPLA2)
