Endocrinology EXAM 2 MATERIAL Cells releasing hormones in the Anterior Pituitary The anterior pituitary contains cells that express receptors that bind to hypothalamic hormones released via the hypothalamic hypophyseal portal system Cell types in the anterior pituitary that respond to hypothalamic hormones to synthesize release other hormones The target cells are themselves autocrines 1 Somatotrophs are the target cells for GHRH growth hormone releasing hormone and GHIH growth hormone inhibiting hormone release Growth Hormone GH a Under the influence of GHRH the somatotrophs respond to GHRH to synthesize and b GHIH inhibits the somatotrophs from synthesizing and releasing GH i GHIH is also referred to as a somatostatin 2 Lactotrophs stimulated to synthesize release the hormone prolactin a Lactotrophs are inhibited by prolactin inhibiting hormone PIH aka dopamine b Lactotrophs are stimulated by prolactin releasing hormone PRH 3 Thyrotrophs are stimulated by TRH to synthesize release thyroid stimulating hormone TSH a Not all cells are under the influence of a releasing hormone and an inhibiting hormone have to find a way to turn this off thyroid hormones feed back to inhibit by negative feedback 4 Corticoitrophs are stimulated by CRH to synthesize release adrenocorticotrophic hormone 5 Gonadotrophs are stimulated by GnRH to synthesize release 2 hormones ACTH a Inhibited by negative feedback a Luteinizing hormone LH b Follicle stimulating hormone FSH Growth hormone GH Somatotropin Growth hormone is a 191 amino acid polypeptide hormone released by the somatotrophs in the anterior pituitary Growth hormone release declines with age o Children release 1 600 ug 1 800 ug day release more as a child o Adults release 400 ug day Growth hormone is not released into fetal blood therefore you can t often tell if there is a defect early on The effects of GH are seen after birth takes awhile before the physician can see any defects o Always have to adjust for parental heights o Gene for tallness is dominant so that it is still possible to have a short child with two tall parents which could be heterozygous and have short alleles Release more growth hormone when you sleep Plasma half life is 20 min 50 min Factors that affect Growth hormone release Factors that increase growth hormone levels o Increased GHRH secretion from the hypothalamus can stimulate the Somatotrophs to release more GH o Sleep 70 of daily GH secretion occurs during the 3rd and 4th stages of sleep Sleep divided into 4 stages Release more in deep sleep 3rd stage Light also effects release release less when you sleep during the day o Stress emotional physical exercise trauma surgery o Metabolic factors Hyperaminoacidemia high levels of amino acids Amino acids in the blood are used for protein synthesis Hypoglycemia low levels of blood glucose Hormone works to bring glucose back into the blood o Anorexia nervosa and starvation results in hypoglycemia can act as a stimulus o Dopamine PIH agonists o Chronic liver failure results in low levels of IGF which removes negative feedback mechanism that inhibits GH release In normal conditions GH stimulates the hypothalamic cells to synthesize release insulin like growth factors IGF1 and IGF2 aka Somatomedins High levels of IGF will inhibit GH release via negative feedback mechanism Factors that decrease growth hormone levels Increased somatostatin GHIH secretion o o Hyperglycemia high levels of glucose o Hyperlipidemia high levels of fatty acids o Obesity due to persistent hyperglycemia and hyperlipidemia o Severe emotional depression o Dopamine antagonists Paradoxically dopamine agonists SUPPRESS growth hormone levels in acromegaly Biological Actions of Growth Hormone Growth hormone binds to growth hormone receptors that recruit Tyrosine Kinase JAK MAPK STAT signal transduction pathway o Need to dimerize receptor binds to two receptors o JAK will phosphorylate other downstream proteins including STAT and MAPK Biological actions may be direct and indirect Direct biological actions of GH o GH stimulates lipolysis GH is a lipolytic hormone Break down fatty acids and feed into the energy pathways Indirect biological actions of GH o GH inhibits cellular uptake of glucose resulting in increased blood glucose levels GH is an insulin antagonist cellular uptake of glucose GH is a diabetogenic hormone GH increases blood glucose levels by preventing Neurons liver and skeletal muscles are some of the major users of glucose and are all insulin dependent they must be able to pick up glucose o GH stimulates the production of IGFs Insulin like Growth factors by hepatocytes o GH stimulates the production of IGF 1 and IGF 2 which then stimulate postnatal longitudinal bone growth IGFs stimulate proliferation of cartilage epiphyseal plates and growth of the organs o Growth hormone via IGF synergizes with sex steroid hormones to cause adolescent growth spurt An increase in GH increase in IGR increase linear bone growth by the IGFs stimulating growth of the epiphyseal plates and ossification of the long bone abutting the epiphyseal plates Lengthen shaft diaphysis which will lengthen the bone and increase height Add hylein cartilage to epiphyseal plates top and bottom the same amount will be turned into bone tissue shifting top superior and bottom inferior plate shifting When GH is released after the plates close due to high levels of the sec steroid hormones you see widening of bones that would otherwise growth tall o Stimulates cellular uptake of amino acids and protein synthesis o Hence the growth promoting effects of GH are indirect via IGF actions Abnormal Growth Abnormal growth is not always due to growth hormone dysfunction there are many other causes Some causes of short stature o Hypothalamic dysfunction hyposecretion of GHRH o Pituitary dysfunction GH deficiency in childhood results in dwarfism o GH receptor insensitivity Laron s dwarfism o Hypothyroidism o Vitamin D deficiency rickets o Chronic renal disease o o Chromosomal abnormalities such as Down syndrome Turner s syndrome o Pseudohypoparathyroidism o Chronic renal diseases o Progeria rare genetic disease with aging symptoms There are a lot of causes of abnormal growth rather than just growth hormone IGF Somatomedin deficiency resistance pygimies Progeria Currently there are less than 40 cases reported worldwide According to the Mayo Clinic since Progeria or Hutchinson Gilford Progeria Syndrome is extremely rare 1886 only 130 cases have been