Ch4 Adrenal glands

• The adrenal glands consist of three (and a half) glands in one: the cortical zona glomerulosa which is responsible for salt homeostasis, the cortical zona fasciculata which is part of the HPA axis and stress response, the cortical zona reticularis which is responsible for reproduction, and the medulla which is responsible for the sympathetic nervous system broadcast.
• The other functions of adrenal catecholamines include increasing BMR by 30%, increasing glycogenolysis in the liver, and stimulating glycogenolysis in muscles followed by rapid local ATP synthesis and production of lactate, also known as the Cori cycle.
• Adrenal catecholamines increase thermogenesis in brown adipose tissue, a process that is permissive.
• Propranolol slows the heart and is used to treat cardiovascular disease and anxiety.
• The mammalian adrenal gland is located above each kidney and contains two tissue types: chromaffin (adrenaline-releasing) and adrenocortical (corticosteroid-releasing) tissue.
• Both types of adrenal tissue are also found in neighboring regions of the body cavity.
• The adrenal cortex is subdivided into zones: the zona glomerulosa which produces mainly aldosterone and deoxycorticosterone (mineralocorticoids), the zona fasciculata which produces mainly cortisol & corticosterone (glucocorticoids), and the zona reticularis which contains many connective tissue elements and is the source of dehydroepiandrosterone (DHEA) and androstenedione (weak androgens).
• Different adrenal layers release and are controlled by different hormones.
• The adrenal changes during human development are typical for primates and the fetal zone produces relatively large amounts of the weak androgen DHEA as well as some DHEA sulfate.
• Increase in GCs and suppression of the immune response is therapeutic in inflammatory diseases such as rheumatoid arthritis and asthma.
• Cortisone levels correlate with socioeconomic status.
• Changes caused by frequent activation of stress pathways, such as elevation of blood sugar, can have deleterious cardiovascular and metabolic effects.
• Glucose availability plays a role in thermoregulation and control of blood pressure.
• High levels of glucocorticoids (GCs) have immunosuppressive and anti-inflammatory actions, inhibiting production of antibodies and cytokines and increasing synthesis of anti-inflammatory proteins.
• Glucocorticoids block inflammation pathways by inhibiting NF-κ B and AP-1, important transcription factors in inflammation pathways.
• Activated glucocorticoid receptor (GR) directly interacts with NF-κ B and AP-1 to block their activity.
• The mammalian adrenal gland has a connection between stress and cortisone levels.
• Powerful synthetic glucocorticoids are used clinically, for example, in organ transplants.
• GR has other anti-inflammatory actions, for example, blocking histamine secretion from mast cells.
• High stress causes higher cortisone levels in blood.
• Cytokines can enter the brain via the circumventricular organs and activate CRH secretion.
• The fetal zone is situated between the cortex and the medulla and is important for maintaining pregnancy as the placenta cannot synthesize androgens and uses fetal adrenal androgens as precursors for estrogen synthesis.
• The synthesis of corticosteroid precursor involves the steps C21, C18, C19, C21, C21, C19, C21.
• Desmolase converts 27 carbon sterol to 21 carbon sterol, all corticosteroids are derived from pregnenolone.
• Glucocorticoids (GC) bind to more than 90% to corticosteroid-binding globulin (CBG), the bound fraction functions as a hormone reservoir.
• The synthesis of glucocorticoids and androgens depends on ACTH stimulation.
• Corticosteroids are not stored in the adrenal, circulating levels reflect synthesis rate.
• Biosynthesis and transport of corticosteroids involve the mammalian adrenal.
• Mineralocorticoids are synthesized in the zona glomerulosa.
• Weak androgens are synthesized in the zona reticularis (and fetal zone).
• Circulating glucocorticoid levels show a circadian rhythm with high levels in the morning (diurnal mammals) or evening (nocturnal mammals).
• The synthesis of aldosterone is mainly regulated by the renin-angiotensin system.
• The liver is the major site of metabolism of corticosteroids, the kidney and intestine also contribute.
• Most corticosteroids are conjugated with sulfates or glucuronides, this increases in water solubility and followed by excretion via urine, bile or faeces.
• Glucocorticoids are synthesized in the zona fasciculata.
• Aldosterone does not bind significantly to plasma proteins, has lower levels and is cleared more rapidly.
• ACE2 protease inactivates angiotensin II.
• ANP acts through a receptor guanylyl cyclase: activation generates second messenger cGMP.
• Angiotensin type 1 receptor (AT1) and MAS protooncogene receptor (MAS1) are involved in the actions of angiotensins.
• ANF inhibits sodium reabsorption by inhibiting both ENaC and the sodium/potassium ATPase through PKG-dependent phosphorylation.