BISC 307L 2nd Edition Lecture 17 Current LectureAnatomy of the Adrenal GlandAdrenal cortex – adrenal gland is ontop of the kidney. It has two parts – anouter cortex and inner medulla (whichsynthesizes catecholamines likeepinephrine). For now we will focuson the cortex. (coid = steroid, corti =from the adrenal cortex)The cortex has 3 layers:1. Zona glomerulosa, the outer layerwhich secretes mineralocorticoids.These are involved with ion andmineral balance in the body. The mainone 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 sourceof estrogenichormones in thebody is the adrenalcortex. It becomesimportant inmaintaining libido,bone strength,muscle strength,etc.Steroid Hormone SynthesisDon’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 importantbecause 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 steroidhormones. 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 SecretionFar right = cortisol beingsecreted from adrenalcortex. Secretion ofcortisol is under thedirect control of ACTH, atrophic hormonesecreted by a specific cellin the anterior pituitary.Trophic hormone =supports growth andhormone synthesis froman endocrine gland(adrenal cortex in thiscase). ACTH’s release isregulated by releasinghormones 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 inthe 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 hypothalamusto 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 AdrenalCortexLeft = left adrenal gland.Right = same but cutdifferently.The patient in the middleis normal. The adrenalmedulla (dark inside) hasa normal volume. At the bottom are adrenalglands from patients with cushing’s disease. The adrenal cortex is tremendously hypertrophied due