BISC 307L 2nd Edition Lecture 17 Current Lecture Anatomy of the Adrenal Gland Adrenal cortex adrenal gland is on top of the kidney It has two parts an outer cortex and inner medulla which synthesizes catecholamines like epinephrine For now we will focus on the cortex coid steroid corti from the adrenal cortex The cortex has 3 layers 1 Zona glomerulosa the outer layer which secretes mineralocorticoids These are involved with ion and mineral balance in the body The main one in humans is aldosterone and it has two targets distal part of kidney tubules where it stimulates sodium reabsorption from tubular fluid back into blood and potassium secretion from blood into tubular fluid It does the same thing in the large intestine 2 Zona fasciculate the middle part where glucocorticoids come from Gluco means they have to do with levels of glucose It will be the main subject of today s lecture 3 Zona reticularis innermost layer secretes androgens It is not important in men because we have much higher levels of testosterone so much that they overshadow the androgens being secreted by the zona reticularis But in women after menopause ovarian follicles stop cycling and the only source of estrogenic hormones in the body is the adrenal cortex It becomes important in maintaining libido bone strength muscle strength etc Steroid Hormone Synthesis Don t need to memorize this It is a simplified view of the pathway for synthesis of steroid hormones There are lots of details left out Some of the intermediates in the boxes aren t labeled The main take away is that all these steroid hormones are synthesized from cholesterol and are related structurally Many of the important ones in the colored boxes are related to the others as products or precursors After a couple of steps cholesterol is converted to progesterone which is the precursor for synthesis of corticosterone and cortisol These two hormones are the main glucocorticoids we are focusing on In humans cortisol is more abundant than corticosterone which is the precursor to aldosterone Progesterone and other intermediates are precursors to androstenedione and so is DHEA Androstenedione is important because it is the precursor to testosterone Progesterone estrone and estradiol are the main female hormones Estrone and estradiol are the estrogens which is a term that covers functionally steroid hormones in humans Androgen is a collective term for the steroid hormones in males Main ones being testosterone and dihydrotestosterone Also in about half of the places in the male body where testosterone acts to promote maleness it is aromatized to estradiol and it binds estrogen receptors So it doesn t necessarily activate testosterone receptors All of these steroid hormones are water soluble and lipid insoluble so they cannot be synthesized in advanced and stored in vesicles because they would diffuse right out Synthesized on demand mostly by oxidases in mitochondria And once synthesized and released they just take off Not very soluble so they diffuse and travel bound to carrier proteins For cortisol and corticosterone the specific plasma proteins are the CBG s or transcortin The other very important carrier for glucocorticoids and other steroid hormones is the most abundant plasma protein albumin and amongst other functions it binds and transports steroid hormones It s not just in the watery plasma that the steroid hormones have to be transported by being bound to binding proteins but also in the extracellular fluid and intracellular fluid and so on Control of Cortisol Secretion Far right cortisol being secreted from adrenal cortex Secretion of cortisol is under the direct control of ACTH a trophic hormone secreted by a specific cell in the anterior pituitary Trophic hormone supports growth and hormone synthesis from an endocrine gland adrenal cortex in this case ACTH s release is regulated by releasing hormones from the hypothalamic neurons There are two of them which are released into the capillary of the median eminence which drains into a small vein that goes to the anterior pituitary where it breaks up into another capillary bed and releases more hormones onto the hormone secreting cells of the anterior pituitary The small blood vessel that drains capillaries in the median eminence at the top of the stalk of the pituitary carries those hormones to the anterior pituitary By definition a vein which has capillaries at both ends a portal vein Only 3 or 4 in whole body If you think about it most veins have capillaries at the upstream end and the heart at the downstream This small vein has them at both ends It goes from hypothalamus to anterior pituitary so it is called the hypothalamic hypophyseal portal The main releasing hormone from the hypothalamic neurons is called CRH And it causes release of ACTH Another one ADH is also a releasing hormone in the brain Dashed lines show inhibition Can see long and short loop feedback inhibition ACTH goes back and inhibits hypothalamus Cortisol itself feeds back and inhibits both the hypothalamus and Anterior pituitary Longer loop Back to hypothalamus What controls its secretion Many factors including diurnal rhythms seen in graph at upper right corner which has levels in nanomolars of ACTH as a function of time day At 4 6 AM it peaks just before you wake up Then it declines and reaches its lowest level around bedtime then increases while you are sleeping It goes from 100 to 1000 so there is a big range of concentration So timing is important when sampling or testing cortisol levels At the bottom we have lymphokines a class of cytokines messengers that lymphocytes use to communicate with each other They powerfully affect the hypothalamus and inhibit the system reducing levels of cortisol Parasympathetic activity tends to inhibit it And related to that is the important effect of stress Stress is the most powerful influence on the hypothalamus to control this system Stress of any sort will trigger it Starvation anxiety tissue trauma like surgery infection exposure to intense heat cold restraints etc Pathology of the Adrenal Cortex Left left adrenal gland Right same but cut differently The patient in the middle is normal The adrenal medulla dark inside has a normal volume At the bottom are adrenal glands from patients with cushing s disease The adrenal cortex is tremendously hypertrophied due to a primary tumor in the cells of the pituitary gland that secrete ACTH a pituitary adenoma a type of pituitary cancer of the cells