The Adrenal Glands 1 Adrenal Cortex Introduction The hormones produced by the adrenal glands clearly play a vital role in the regulation of the body s homeostasis Anatomically the adrenal glands are associated with the superior poles of the two kidneys Composed of an outer part called the cortex and a central medulla only the adrenal cortex is vital for life Adrenal embryology and general structure The fetal adrenals are detectable from around the sixth week in utero Adrenal cortex develops from clusters of mesenchymal cells along the developing coelomic cavity wall close to the urogenital ridge Each adrenal cortex consists initially of an inner fetal and an outer permanent zone During the first year postpartum the inner fetal zone regresses while the permanent zone proliferates and differentiates into outer glomerulosa and inner fasciculata zones An additional even more inner zone reticularis develops subsequently Neural crest cells form the medulla chromaffin cells Each adrenal gland lies within its own capsule attached to the upper pole of its respective kidney cid 127 Weighs about 5 g and is pyramidal left or crescent shaped right intercostal arteries Radial capillaries pass through the three cortical zones to reach the adrenal medulla Blood then enters a central vein in the middle of the medulla Passes through the short right adrenal vein to train directly into the inferior vena cava Blood reaches each adrenal gland by a number of small arterial branches from the abdominal aorta as well as from the interior phrenic the renal and the Blood from the longer left adrenal vein usually drains into the left renal vein or sometimes into the left inferior phrenic vein before entering the vena cava Synthesis storage release and transport of the adrenocortical hormones The zona glomerulosa represents the outer 15 of the cortex the main part approximately 75 being the radial rows of cells comprising the zone fasciculata cid 127 Glomerulosa cells are small and grouped together in spherical clusters Fasciculata cells are larger and full of lipid and extend towards the innermost reticularis cells which are irregularly distributed and contain little lipid The chromaffin cells of the medulla are clearly different and separate being typical secretory cells with many granules The three cortical zones are associated with steroid hormones called corticosteroids Cannot be stored to any great extent as they would simply cross the lipid membranes of cells and move into the general circulation once synthesized Historically the hormones have been classified according to their principal physiological activities Hormones having a major role in mineral Na K ions regulation called mineralocorticoids Hormones having a major role in metabolic regulation called glucocorticoids Hormones more commonly associated with the gonads the sex hormones estrogens and androgens The first important step in corticosteroid hormone synthesis is the rate limiting transport of intracellular cholesterol across the outer to the inner mitochondrial membrane where in the presence of the enzyme P450scc it is converted to pregnenolone A specific steroidogenic acute regulatory stAR protein mediates this transport process which is controlled by the adenohypophysial hormone corticotrophin ACTH The pregnenolone enters the cytoplasm where is is converted to progesterone by the enzyme 3beta hydroxysteroid dehydrogenase Subsequent conversions are dependent on the specificity of enzyme present in the cells of the three zones and their specific intracellular location In the glomerulosa cells progesterone is converted to deoxycorticosterone by 21 hydroxylase which is found in the microsomes and endoplasmic reticulum Then converted to corticosterone by the mitochondrial enzyme 11beta hydroxylase In humans corticosterone is converted to the far more potent molecule aldosterone by aldosterone synthase The fasciculata and reticularis cells contain 17alpha hydroxylase which is absent from the glomerulosa cells Located in the micoromal endoplasmic reticulum it converts both pregnenolone and progesterone to their 17alpha hydroxy metabolites 17alpha hydroxypregnenolone can be converted to 17alpha hydroxyprogesterone by the 3beta hydroxysteroid dehydrogenase enzyme cid 127 Mainly in the fasciculata cells the 17alpha hydroxyprogesterone is converted to 11 deoxycortisol by the enzyme 21 hydroxylase This in turn is converted by 11beta hydroxylase to the the final end product in humans the powerful glucocorticoid cortisol Both 17alpha hydroxypregnenolone and 17alpha hydroxyprogesterone can also be converted to the weak androgens DHEA and androstenedione respectively by the action of 17alpha hydroxylase these actions take place mainly in the reticularis cells In humans the principal mineralocorticoid produced by the zona glomerulosa is aldosterone while the principal glucocorticoid is cortisol hydrocortisone Cortisol is inactivated to cortisone by 11beta HSD2 and reactivated by 11beta HSD1 The weak androgens produced DHEA and androstenedione can be converted to more potent androgens and estrogens in peripheral tissues depending on whether reductase or aromatase enzyme are present in the cells The adrenal androgens represent approximately 50 of the circulating androgens in females the reminder coming from the thecal cells of the developing ovarian follicles and the corpus luteum testosterone and DHT produced by the testes In males the adrenal androgens are normally of little significance since the majority of the circulating androgen content is provided by the more potent The corticosteroid hormones are believed to simply diffuse across the lipid comments of membranes once they have been synthesized cid 127 Once in the circulation over 90 of the corticosteroids are bound to plasma proteins cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 The total circulating concentration of cortisol is far greater than that of aldosterone The two main plasma proteins involved in corticosteroid transport are a specific high affinity alpha2 globulin synthesized in the liver called transcortin or CBG and the non specific low affinity but high capcity albumin Transcortin binds most of the