I recettori intracellulari

I recettori intracellulari sono recettori per ligandi lipofili che penetrano passivamente nel citoplasma e/o nel nucleo per diffusione passiva. Essi sono proteine citoplasmatiche o nucleari che, in seguito all’interazione col proprio ligando, sono in grado di modulare la trascrizione genica. I recettori intracellulari rappresentano il bersaglio molecolare degli effetti degli ormoni steroidei e tiroidei, dei retinoidi e delle vitamine D ed A. Gli ormoni steroidei, ad esempio, grazie alla loro struttura idrofobica, attraversano la membrana cellulare e si legano a specifici recettori intracellulari. Quando avviene questo legame, la struttura ormone-recettore viaggia verso il nucleo dove si legherà a sequenze di DNA ben definite. Queste sequenze, prendono il nome di “elementi di risposta ormonale” (HRE) e sono situati a monte di un promotore genico. Il legame del recettore allo specifico HRE può avviare un processo attivo (regolazione positiva) o inibitorio (repressione) sull’espressione genica. Dunque, a seconda del processo si avrà o meno la trascrizione di geni specifici.

Sito di attivazione

Il meccanismo di attivazione dei recettori intracellulari, come già accennato, avviene nel citoplasma o nel nucleo a seconda della classe di ormoni considerata. Ad esempio, i recettori per alcuni ormoni corticosurrenalici, come l’aldosterone, in condizioni di riposo, sono localizzati nel citoplasma. Essi, arrivano al nucleo solo dopo la loro attivazione da parte del ligando. Altri recettori, invece, sono associati anche in condizioni di riposo a strutture nucleari. Di questi recettori, ricordiamo quelli per gli ormoni tiroidei, estrogeni, vitamina D e per l’acido retinoico. Ci sono poi alcuni recettori che sono inattivi nel citoplasma e che vengono attivati col distacco di alcune subunità inibitorie (proteine Hsp). Di questa tipologia sono i recettori per i glucocorticoidi e per il progesterone. Quando questo tipo di recettore viene attivato, arriva al nucleo in forma di dimero dove si lega ad una sequenza palindromica di DNA (Glucocorticoid Response Element, GRE). Questa sequenza è situata a monte di promotori per specifici geni di cui regolano l’attività sia in senso positivo che negativo.


Recettore intracellulare che lega un attivatore (ormone) e viaggia verso il nucleo dove permette l'alterazione della trascrizione genica. Fonte: Summa Gallicana
Recettore intracellulare che lega un attivatore (ormone) e viaggia verso il nucleo dove permette l’alterazione della trascrizione genica. Fonte: Summa Gallicana

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