BISC 307L 2nd Edition Lecture 19 Current Lecture Growth Hormone Effects Indirect effects are due to induction of IGF synthesis and secretion within target cells Among these target cells IGF production in the liver was particularly important because of the amount of IGF production spilling out of the liver and becoming a circulating growth hormone for the rest of the body For most other tissues IGF acts locally as a paracrine hormone to stimulate the growth of that tissue Those are the indirect and most powerful effects Direct widespread Stimulates many anabolic reactions protein RNA synthesis lipolysis in adipose tissues Overall lean body mass due to increase in muscle growth fat content in adipose tissue Increased organ size especially in bones heart and lungs Effects on long bones important in determining height Control of Growth Hormone Secretion Control follows the classical hypothalamic and anterior pituitary pathway If we start with growth hormone secretion from somatotropes of the Anterior Pituitary the release of GH is directly stimulated by GHRH There is also a hypothalamic release inhibiting hormone called SS So there is dual hypothalamic control of the secretion of GH from the ant pit GH affects many different target cells indirectly GH works through 3 different stimuli for growth direct effect of circulating growth hormone on target cells an indirect effect mediated through IGH produced in the target tissue and an indirect effect mediated by IGF produced by the liver and circulating through the body as a hormone So IGF acts as both a circulating hormone and a paracrine hormone The negative feedback is typical the peripheral hormones IGF and GH feedback and inhibit the releasing hormone and the GH itself as shown by the dashed arrows Patterns of GH secretion originate in the hypothalamus Can see that there is a strong age dependent pattern to GH release In fetal life it doesn t have much effect but it has a strong effect in prenatal life After birth GH secretion is highest in childhood reaching a peak at puberty Then it starts a slow and steady decline from that point throughout the rest of life In midlife and advanced age GH is still secreted but at lower levels A fall in plasma glucose from a high level like after a meal will cause an increase in secretion of GH Insulin will take care of moving the fuel molecules from the plasma into glycogen stores and fat stores as we ve discussed Then what happens That energy stored in those forms can be utilized to power tissue growth by a subsequent bout of secretion of growth hormone Makes it possible for food you ate to actually go into RNA protein synthesis and growth and maintenance of tissue Growth Hormone Pathologies Dwarfism Caused by a deficiency in growth hormone secretion or a deficiency in GH or IGF Receptors because GH works through IGF in childhood Not very common anymore because recombinant human growth hormone has become available to treat this Gigantism and Acromegaly Effects of over secretion of GH If it occurs in childhood it results in gigantism Shown in the picture are twin brothers Normal on right giant on left This is more difficult to treat because it involves treating a tumor radiation therapy etc are necessary A second manifestation of GH oversecretion is acromegaly GH oversecretion occurring in adulthood whether or not it happened in childhood Bones grow during childhood and adolescence at their ends But when the long bones stop growing growth stops So bones can still grow but they can t grow in length instead grow in thickness or girth This causes a disfiguring condition and limits mobility and is extremely painful Acromegaly patients usually die young Gestational Diabetes Mellitus it had been recognized for a long time that women who were diabetic before they became pregnant had a worsening of their diabetic condition during pregnancy When this happened the outcome for the newborn had a higher chance of being poor originally thought to be reversible temporary standard method for accessing the diabetic condition is called the oral glucose tolerance test The test consists of having a person fast for 12 hours and then consume a syrupy liquid of glucose to drink and then measuring plasma glucose levels in the person What you should see is illustrated by the solid line on the bottom of the graph to the right On the Y axis is plasma glucose concentration and on the x axis is the hours after giving the glucose Patient A on the bottom shows a normal response Plasma glucose at the beginning isn t too high but it gets higher over the next hour and within an hour or two it falls back down to normal levels This is due to the action of insulin A person who has diabetes would look like the line at the top of the graph At time 0 blood glucose is already elevated They have an elevated resting plasma level It rises to alarmingly high levels without plateauing and peaks and falls as there is eventually some insulin action but the fall is much slower This kind of pattern is called glucose intolerance On the bottom of the graph is shown normal glucose tolerance insulin handles it for you Upper curve abnormal Used to measure the extent of diabetic or pre diabetic condition So this worsening of diabetes in women occurs but not just in diabetic women Women who were not diabetic before they got pregnant also developed glucose intolerance during pregnancy After testing the oral glucose tolerance test on a number of women the findings reported that women who were not diabetic pre pregnancy had lower risk of getting diabetes after pregnancy and that the higher the glucose intolerance before pregnancy the more likely they would develop diabetes sooner Two realizations have come out of this research 1 Development of insulin resistance during pregnancy is normal and occurs in all women 2 Changes in the glucose intolerance test are caused by insulin resistance that is the mothers tissue becomes less sensitive to secreted insulin during pregnancy However most women during pregnancy do not show any kind of diabetic condition because as insulin resistance of her tissue increases during pregnancy Starting during the second half of pregnancy the beta cells compensate for this So in response to insulin resistance beta cells secrete more insulin such that insulin levels go high in the mother during pregnancy If everything goes right plasma glucose doesn t elevate much at all or is only slightly abnormal One leading theory of what causes