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Forelesningsserie, veksthormon(er) v/Jan O. Gordeladze • Endokrin regulering av: • vekst (veksthormon) • basal metabolisme (også thyroideahormoner) • ”alt mulig” (også glukokortikoidhormoner) Endokrin regulering • Endokrine kjertler frisetter kjemiske forbindelser, hormoner, fra kjertelceller til ekstracellulær væske, blod • Diffunderer og transporteres gjennom kroppen • Reagerer med spesifikke reseptorer for å fremkalle cellulære endringer. Endokrine Kjertler • 7 hovedgrupper: • • • • • • • Hypofyse Skjoldbruskkjertel (thyroid gland) Biskjoldbruskkjertel (parathyroid) Testis Ovary Adrenal gland Pancreas • Pluss CNS, tarm, lokale celler (”faktorer”) Hormongrupper • Peptider: insulin, glukagon, ACTH, GH, TSH, TRH • Aminosyrederivater: katekolaminer, indolaminer, tyrosinderivater • Steroider: aldosteron, kortisol, progesteron, østrogen, testosteron Hormonmetabolisme • Syntese: i spesifikke celler • Frisetting: eksocytose eller andre mekanismer • Transport: Fritt i plasma (peptider, aminosyrer) vs. proteinbundet (steroider) • Nedbrytning: Oftest lever, nyre • Utskilles: Urin, tarm Funksjonell homeostase • Enkel tilbakemelding (”feed back”) • Eksempel: nivåer av glukose – ßceller insulin - glukose • Hierarkisk regulering: via CNS, hypofyse. • Eksempel: binyrebarkhormoner - CRH - ACTH binyrebarkceller Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier Growth hormone (somatropin) • Protein, 2(3) variants, 191 or 176 a.a. • Synthesized in somatotrophs in anterior pituitary • Stored in secretory granules, released by Ca2+dependent exocytosis Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier Effects of GH • Acute effects – diabetogenic: • • • • Decrease glucose uptake Increase lipolysis Increase glukoneogenesis Induce insulin resistance • Long Term Effects – bodily growth: • Mediated by insulin-like growth factor-I (IGF-I) • IGF-I is synthesized/released by GH-receptor activation in most tissues • IGF-I receptor: tyrosine kinase – ras-mediated effect. Veksthormon= Growth Hormone = GH VIRKER på nesten ALT VEV Tyrosin-kinase reseptoren dimeriserer, fosforyleres og P-grppene binder forskjellige signalproteiner Tyrosinkinase-assosiert reseptor GH virker via en tyrosinkinaseassosiert reseptor Tyrosin kinase reseptorer IGF virker via en tyrosin-kinase reseptor. Her er tre typer av disse reseptorene Akromegali Gigantisme Akromegali eller gigantisme • ØKT SEKRESJON AV VEKSTHORMON FØR AVSLUTTET LENGDEVEKST: GIGANTISME • ØKT SEKRESJON AV VEKSTHORMON ETTER AVSLUTTET LENGDEVEKST: AKROMEGALI Dvergvekst • MANGLENDE SEKRESJON AV VEKSTHORMON I OPPVEKSTEN (kan også skyldes manglende reseptor for GH) • KORTVOKST; under 120 cm, men med normale proporsjoner • Hvis ikke andre hormonforstyrrelser, normal kjønnsutvikling Quiz: Er de fysiologiske effektene av veksthormon alltid direkte på målcellene? Begrunn svaret. Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier IGF-I-mediated regulation of GH release • IGF-I effects on CNS • on anterior pituitary somatotrophs Downloaded from: StudentConsult (on 28 January 2011 01:28 PM) © 2005 Elsevier Other growth-regulating hormones • Thyroid - lack of gives cretinism, dwarfism • Cortisol - lack of gives dwarfism • Sex hormones – puberty determines end of growth period • Insulin - lack of gives Langerhans’ islets «type» dwarfism Clinical Relevance • Before puberty • Lack of GH/IGF-I: dwarfism (0.9 m body size) • Excess of GH/IGF-I: gigantism (2.7 m body size) • After puberty (growth zones closed) • Excess of GH/IGF-I: Acromegaly (expansive skeletal growth, multiple problems, diabetes, heart failure etc) Multiple choice 1-5: Which of the following statement(s) is/are false? 1) GH-release from the pituitary is stimulated by GHRH, but inhibited by Somatostatin (ST) 2) GH-release is mediated by the PLC-pathway (enhanced DAG and IP3) via mobilization of intracellular Ca2+. 3) The acute effects of GH are: decreased glucose uptake, increased lipolysis, decreased gluconeogenesis, induced insulin resistance, enhanced lean body mass. 4) GH-induced IGF-1 (synthesized by the liver) is inhibiting the GH-release via negative feed-back on GHRH-secretion, and negative feed-back on ST (hypothalamus), and direct negative feed-back on the pituitary. 5) The pubertal peak rate of growth corresponds to the peak serum concentration of IGF-II.
