Anterior Pituitary Growth Hormone Factors that affect Growth hormone release Factors that increase growth hormone levels Increased GHRH secretion SLEEP 70 of daily GH secretion occurs during the 3rd and 4th stages of sleep Stress emotional physical exercise trauma surgery Metabolic factors hyperaminoacidemia hypoglycemia Anorexia nervosa and starvation result in hypoglycemia Dopamine agonists Chronic liver failure due to the absence of negative feedback by IGF Factors that decrease growth hormone levels Increased Somatostatin GHIH secretion Hyperglycemia Hyperlipidemia high levels of fatty acids Obesity due to persistent hyperglycemia and Hyperlipidemia Severe emotional deprivation Dopamine antagonists Biological actions of growth hormone Direct effects 1 Antagonizing insulin dec in glucose uptake by insulin dependent cells hence inc glucose levels in blood reise to proved glucose to the neurons glucose sparing effect of GH Increase gluc levels in blood GH diebtogenic hormone a b High levels of GH above physiological levels diabetes mellitus 2 Since cells cant pick up glucose from blood except neurons GH breaks fown lipids to provide substrates for catabolic by cells to provide energy GH stimulates liposis breakdown of lipids hence GH is reffered to as lipithtic hormone a Would you recommend GH for weight loss 3 GH binds to GH recept on hepatocytes liver cells to stimulate the hepatocytes to produce insulin like growth factors 4 GH also stimulates the cellular uptake of amino acids b c GH is released in response to hyperaminoacidemia cellular uptake of amino acids inc protein synthesis Stimulates the lengthening of long bones Inc GH inc IGF inc chrondroblasts inc hyaline cartilage in the proliferative zone of the epithelial plate Convert ossification zone into bone tissue in kids where epiphyseal plates are present the amount of hyaline cartilage added into the proliferative zone about the epiphysis is the same as the bone tissue added in the ossification zone about the diaphysis o Maintain the thickness of the epiphyseal plate but the plate has shifted away from the diaphysis inc the length of the diaphysis Indirect effects o Inc diaphysis of a long bone results in inc height long bones in lower legs o GH has an indirect effect on heights attained bipeds o At after puberty the sex steroid hormones gonanadal steroids androgens in males testosterone estrogens in females estradion o At the beginning of puberty the sex steroid horms synergize with GH to inc IGF production by the hepatocytes o GH sex steroid hormones high levels of IGF high levels of chronfroblast proliferation high levels of hyaline cartilage in proflieration zone inc osteoblasts in sdlf zone inc diaphysis growth spurt in adolescence o At a critical sex steroid hormone level which is very high the sex steroid hormones antagonize GH action at the hepatocytes dec IGF b c levels of GH are going down with age edc chrondroblasts dec hyaline cartilage in prolif zone sex steroid hormones will stimulate osteoblast activity inc ossification in ossify zone and over time the entire epiphysical plate besomes ossified leaving a remnant called the epiphyseal line epipheseal closure height is determined 10 9 missed 10 7 and 10 4 Hypofunction Growth hormone hypofunction in children causes dwarfism o Clinical Features of dwarfism Short stature Delay in skeletal maturation Obesity with pudgy face and fingers due to lack of the lipolytic effect of GH High pitched voice absence of thickening of vocal cords Hypoglycemia due to lack of the diabetogenic effects of GH Hypoglycemic seizures not enough glucose available for neurons neurons including those in the brain use exclusively glucose in aerobic respiration to produce energy GH deficiency low or negligible GH levels in blood GH receptor dysfunction GH in sensitivity laron s cyndrome laron s dwarfism GH levels are higher than normal in individuals cage matched normal indivs IGF deficiency low or negligible IGF levels in blood due to abnormalities of hepatocytes responding to GH to produce IGF Hence chronic liver failure esp in children is associated with short stature IGF deficiency is observed in the ppygmies o GH levels are normal above levels compared to age matured indivs If GH deficiency is established in a child do diagnostic tests to confirm suspicion o Excersice challenge test Purpose excerise stress which induces GH release Test after vigerous exercise take blood samples and measure GH levels If GH levels are still low negligible GH deficiency is confirmed If GH levels are not conclusively low do subsequent diagnostic tests o Arginine infusion test Purpose infuse a a arginine creates hypoaminoacidemia strong stimulus for GH release Test Collect blood sample to measure GH levels Result still low negligible GH deficiency confirmed o Insulin Tolerance test ITT performed under medical supervision to prevent hypoglycemic coma in a GH deficient child Cells will pick up gucose in blood and deprice neurons of glucose lack of glucose sycopic episodes fainting and eventually hypoglycemic coma death Test to create extreme hypoglycemia strongest stimulus for GH release Insulin is given as an IV bolus to create severe hypoglycemia in 20min Hypoglycemia stimulates GH release Results Normal individuals substantial increase in GH levels above the basal GH level GH deficient children NO increase in GH levels still low negligible levels Hypofunction Treatments In GH deficient children Human Growth Hormone hGH replacement therapy these children eventually produce antibodies against the recombinant DNA hGH In Laron s dwarfism IGF 1 replacement therapy Pygmies IGF 1 replacement therapy if treatment is desired Pygmies may also have IGF receptor dysfunction Prolactin Factors that stimulate Prolactin release PRH Pregnancy due to high levels of Estrogens Nursing nipple stimulation causes Prolactin release via a neuroendocrine reflex Seizures Dopamine antagonists Pituitary tumor Primary hypothyroidism due to lack of the thyroid hormones the negative feedback on TRH is absent hence TRH levels high levels of TRH stimulate Prolactin release Factors that inhibit Prolactin release PIH Dopamine dopamine agonists such as Bromocriptine Primary hyperthyroidism causes low levels of TRH Hypophysectomy Lesions in the pituitary or in the brain PIH Dopamine 2 forms of evidence 1 Dopamine agonists such as Bromocriptine inhibit prolactin release used to prevent prolactin release post partum if lactation is not