Anterior Pituitary: Growth HormoneFactors that affect Growth hormone releaseFactors 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 IGFFactors 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 antagonistsBiological actions of growth hormoneDirect effects1. 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 GHa. Increase gluc levels in blood GH diebtogenic hormoneb. High levels of GH above physiological levels diabetes mellitus2. Since cells cant pick up glucose from blood (except neurons), GH breaks fownlipids to provide substrates for catabolic by cells to provide energy—> GH stimulates liposis (breakdown of lipids), hence, GH is reffered to as lipithtic hormonea. 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 factors4. 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 synthesisIndirect effects- 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 diaphysiso 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=estradiono At the beginning of puberty, the sex steroid horms synergize with GH to inc IGF production by the hepatocyteso 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 adolescenceo 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 determined10/9 (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 exclusivelyglucose 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 espin children is associated with short stature. IGF deficiency is observed in the ppygmieso GH levels are normal/above levels compared to age-matured indivs- If GH deficiency is established in a child do diagnostic tests to confirm suspiciono 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 testso 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 confirmedo 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 levelsHypofunction 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 dysfunctionProlactinFactors that stimulate Prolactin release:- PRH- Pregnancy – due to high levels of Estrogens - Nursing – nipple stimulation causes Prolactin release via a neuroendocrine reflex- Dopamine antagonists- Pituitary tumor- Seizures- 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