NEUROENDOKRINA KONTROLA FIZIOLOŠKIH PROCESA ADENOHIPOFIZA
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1 NEUROENDOKRINA KONTROLA FIZIOLOŠKIH PROCESA ADENOHIPOFIZA
2 ADENOHIPOFIZA Identifikovati tri familije hormona adenohipofize i uočiti glavne strukturne razlike među ovim hormonima Objasniti mehanizme regulacije produkcije hormona adenohipofize i delovanje tropnih hormona hipotalamusa Prepoznati mehanizam duge i kratke negativne povratne sprege na primeru pojedinih hormona adenohipofize Pretpostaviti promene koje će nastupiti u organizmu usled smanjene ili prekomerne produkcije ovih hormona Objasniti značaj pulsne sekrecije i dnevno-noćne ritmike oslobađanja hormona
3 Pars distalis Pars tuberalis Pars intermedia
4
5
6
7 Ćelije adenohipofize Neurohormon Hormon adenohipofize Laktotropne Dopamin Prl Kortikotropne CRH POMC: ACTH, β-lph, α-msh, β-endorfin Tirotropne TRH TSH Gonadotropne GnRH LH/FSH Somatotropne GHRH GH Tropni hormoni: TSH, LH, FSH, ACTH, MSH Metabolički hormoni: GH, Prl Podela hormona na osnovu strukturne sličnosti: TSH, FSH, LH - glikoproteini GH, Prl ACTH, MSH, LPH, endorfini, enkefalini
8 Kontrola sekrecije hormona adenohipofize Direktna kontrola - neurohormoni hipotalamusa. Modifikacije odgovora hormonski status povratna sprega dnevno-noćni ritam GH tokom sporotalasnog spavanja (delta aktivnost mozga) TSH i kortizol faze plićeg sna
9 Metabolički hormoni GH AK Somatotropne ćelije, 50% Pulsno oslobađanje Stimulacija GHRH Dopamin Kateholamini Neke AK Inhibicija Somatostatin IGF1 Glukoza SMK T3, T4 grelin <3 ng/ml, 60% vezano za GH-vezujući protein Poluživot: 6-20 min
10 IGF1 70 AK Oko 80% vezano za IGFBP-3
11 Prl AK Laktotropne ćelije, 15-20% Prolaktin Hiperprolaktinemija Stimulacija Serotonin Opioidi GnRH Galanin TRH Inhibicija Dopamin Somatostatin GABA Hipogonadizam 300 različitih funkcija kod kičmenjaka! Roditeljsko ponašanje Ribe balans H 2 O/soli Regulacija rada imunskog sistema Hematopoeza, koagulacija Energetska homeostaza Libido Razvoj mozga,...
12 Tirotropne ćelije 5% Glikoproteini TSH α: 92 AK ljudi 96 AK ostali sisari β: AK Alen i Smith eksperimenti na žabama pokazali značaj TSH i tiroidnih hormona Gonadotropne ćelije 5-10% LH FSH RIBE, VODOZEMCI, GMIZAVCI Endotermni organizmi Faza menstrualnog ciklusa Hormoni gonada GnRH pulsevi Oslobađanje gonadotropina Luteinska - folikulska Niska [estradiola i inhibina] min FSH > LH Srednja i kasna folikulska Povišena [estradiola i inhibina B] 60 min LH > FSH Postovulacija Povišena [estradiola, inhibina A i progesterona] 3-5 sati Sinteza FSH Involucija žutog tela Smanjena [estradiola, inhibina A i progesterona] min FSH
13 Kortikotropne ćelije (10%) Proopiomelanokortinska familija hormona
14 Intermedini (α-msh, β-msh, γ-msh) IRIDOFORE RETINA MSH-RH MSH-IF + - svetlo MSH MELANOFORE
15
16 Poremećaji funkcije adenohipofize Hormon-produkujući adenomi adenohipofize Prolaktinomi (40-45%): hiperprolaktinemija + galaktoreja + hipogonadizam Somatotropni adenomi (20%): akromegalija/gigantizam Kortikotropni adenomi (10-12%): Kušingov sindrom centralna gojaznost, proksimalna miopatija, hipertenzija, promene raspoloženja, hiperglikemija, bizonova grba Gonadotropni adenomi (15%): obično ne utiču na produkciju hormona Tirotropni adenomi (1-2%) Hipofunkcija adenohipofize Najčešći su nedostaci hormona rasta i gonadotropina. Urođeni i stečeni (trauma) oblici. Smanjena osetljivost/neosetljivost tkiva na hormon rasta Laronov sindrom Delecije ili mutacije u genu za GH receptor onemogućuju stvaranje IGF1 i IGFBP-3. Rezultat je patuljast rast.
17 Funkciju adenohipofize kontrolišu: GH deluje na ciljna tkiva direktno i: Laron Z. Insulin-like growth factor 1 (IGF-1): A growth hormone. Mol Pathol. 2001;54:3011. Pritchard LE, Turnbull AV, White A. Pro-opiomelanocortin (POMC) processing in the hypothalamu: Impact on melanocortin signalling and obesity. J Endocrinol. 2002;172:411. Samson WK, Taylor MM, Baker JR. Prolactin-releasing peptides. Regul Pept. 2003;114:1. Tsatmali M, Ancans J, Thody AJ. Melanocyte function and its control by melanocortin peptides. J Histochem Cytochem. 2002;50:125.
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