BISC 307L 2nd Edition Lecture 19 Current LectureGrowth 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 thegrowth of that tissue. Those are the indirect and most powerful effects. Direct – widespread.Stimulates: many anabolic reactionsprotein & RNA synthesislipolysis: in adipose tissuesOverall • 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 heightControl of Growth HormoneSecretion: Control follows the classicalhypothalamic and anteriorpituitary pathway. If we start withgrowth hormone secretion fromsomatotropes of the AnteriorPituitary, the release of GH isdirectly stimulated by GHRH.There is also a hypothalamicrelease-inhibiting hormone, calledSS. So there is dual hypothalamiccontrol of the secretion of GHfrom 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 throughIGH 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 PathologiesDwarfism: 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 iscalled the oral glucose tolerance test. The test consists ofhaving a person fast for 12 hours and then consume a syrupyliquid of glucose to drink, and then measuring plasmaglucose levels in the person. What you should see isillustrated by the solid line on the bottom of the graph to theright. (On the Y-axis is plasma glucose concentration, and onthe x-axis is the hours after giving the glucose.) Patient A, onthe bottom, shows a normal response. Plasma glucose at the beginning isn’t too high, but it getshigher 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 findingsreported 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