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GRELİNİN YAPISI ve ORGANİZMADAKİ FONKSİYONLARI

GHRELIN: STRUCTURE and BIOLOGICAL FUNCTIONS

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Abstract (2. Language): 
Ghrelin, a 28 amino acid peptide hormone discovered in 1999 by Kojima et al., is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. It is secreted mainly by the stomach and n-octanoylation at the third serine residue of this peptide is essential for its bioactivity. Ghrelin stimulates growth hormone release, increases intracellular calcium concentration in somatotrophs by binding its GHS-R1a receptor and also many effects of ghrelin are mediated via the activation of its receptor. Ghrelin participates in modulation of feeding behaviour by acting on hypothalamic arcuate nucleus. Circulating ghrelin levels increase preprandially and decrease after meals. Ghrelin is an only orexigenic hormone which counteracts to leptin. Non-acylated form of ghrelin has also been suggested to have some biological activities such as cell proliferation, lipolysis, adipogenesis and cardiovascular functions. However the binding receptor of non-acylated ghrelin and its biological functions are still unclear. Circulating ghrelin levels are reported to be increased or decreased in response to physiological and pathological alterations. Ghrelin concentrations are shown to decrease in obese subjects and in patients with type 2 diabetes. It is secreted in circadian rhythm showing especially a nocturnal peak at 2 a.m. It is expected that numerous unknown biological functions of ghrelin, particularly those of non-acylated form, will be elucidated by further studies in the near future.
Abstract (Original Language): 
Grelin, 1999 y›l›nda Masayasu Kojima taraf›ndan tan›mlanm›fl bir hormondur. 28 aminoasitten oluflmufl bir polipeptiddir. Dolafl›mdaki grelin miktar›n›n önemli bir k›sm› mideden salg›lan›r ve biyolojik olarak aktif olabilmesi için üçüncü aminoasidi olan serin kal›nt›s›na n-oktanoik asit ba¤lanmas› gereklidir. Grelin, reseptörü olan GHSR1a’a ba¤lanarak hücreiçi Ca konsantrasyonlar›n› artt›r›r, büyüme hormonu (GH) salg›lanmas›na neden olur ve birçok fizyolojik etkisini bu yolla gösterir. Grelin, hipotalamik arkuat nükleusa etki ederek, g›da al›m›n› kontrol eder; açl›kta grelin düzeyleri yükselir, yemek yemeyi takiben düfler. Oreksijenik etkilidir ve leptine z›t etki gösterdi¤i bildirilmifltir. Açillenmemifl (n-oktanoik asit ba¤lanmam›fl) grelinin de biyolojik fonksiyonlar› oldu¤u düflünülmektedir; ancak henüz ba¤land›¤› reseptör ve etki mekanizmas› tan›mlanmam›flt›r. Açillenmemifl grelinin; hücre proliferasyonunda, lipolizde, adipogenezde ve kardivaskuler fonksiyonlarda etkili oldu¤u düflünülmektedir. Fizyolojik ve patolojik de¤iflimlerde, grelin düzeylerinin azald›¤› veya artt›¤› bildirilmifltir. Obezlerde ve tip 2 diyabetli kiflilerde de grelin düzeylerinin düflük oldu¤u gösterilmifltir. Grelin salg›lanmas› sirkadyen ritm gösterir; özellikle sabaha karfl› 2 saatlerinde dolafl›mdaki grelin miktar› en yüksek düzeydedir. Önümüzdeki dönemlerde yap›lacak çal›flmalar›n grelinin birçok bilinmeyen fonksiyonuna ve özellikle açillenmemifl grelinin biyolojik etkilerine ›fl›k tutaca¤› düflünülmektedir.
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