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A Journal on Internal Medicine

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Panminerva Medica 2003 December;45(4):261-6

language: English

Sex steroid receptors, secondary bile acids and colorectal cancer. A possible mechanism of interaction

Berta L., Fronticelli Baldelli C., Fazzari A., Radice E., Bargoni A., Frairia R., Gaetini A.

Department of Clinical Pathophysiology University of Turin, Turin, Italy


Aim. The aim of the ­work was to ­study in ­colon-rec­tum can­cer muco­sae the bind­ing cha­rat­er­is­tics, as sex ster­oid recep­tors.
Methods. Specific andro­gen (AR), estro­gen (ER) and pro­ges­te­rone (PgR) recep­tors ­were meas­ured in the tis­sue sam­ples of 35 ­patients (15 ­males, 20 ­females) under­go­ing colec­to­my or colo­proc­tec­to­my for aden­o­car­cin­o­ma. The char­ac­ter­is­tics of andro­gen recep­tor (AR, DHT-R: dihydrotestosterone receptor) ­were ­also inves­ti­gat­ed ­using com­pet­i­tive activ­ity of cyproterone ace­tate, cortisol, aldosterone and ster­oid-­like sub­stanc­es ­such as deoxicholic and lithocholic ­acid, ­present in the ­milieu of the con­sid­ered ­organ. Binding ­assays and com­pe­ti­tion ­tests ­were con­duct­ed ­using a char­coal dex­tran meth­od.
Results. When ­present (50%), ER and PgR recep­tors ­showed ­very low lev­els and no dif­fer­ence was not­ed ­between can­cer­ous and the sour­round­ing ­healthy muco­sa. AR ­were ­found in all sam­ples ­from ­both neo­plas­tic and non neo­plas­tic sour­rond­ing muco­sa, ­with no sig­nif­i­cant dif­fer­ence. Androgen recep­tor how­ev­er exhib­it­ed an ­altered bind­ing activ­ity in can­cer spec­i­mens. Cyproterone ace­tate did not dis­place DHT ­from AR ­while sig­nif­i­cant dis­plac­ing activ­ity was elic­it­ed by DHT, testosterone, as ­well as by lithocholic ­acid, but not by deoxycholic ­acid.
Conclusion. In can­cer­ous ­large bow­el muco­sa, andro­gen recep­tors ­show ­altered bind­ing carac­ter­is­tics. The selec­tive bind­ing of lith­o­chol­ic ­acid to AR sup­ports the hypoth­e­sis ­that ­diet-relat­ed endo­lu­mi­nal sub­stanc­es may ­play a ­role in can­cer devel­op­ment mod­el ­where molec­u­lar alter­a­tions ­such as DNA dam­age or muta­tion is the ­1st ­event.

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