Sex steroid receptors, secondary bile acids and colorectal cancer. A possible mechanism of interaction.
OBJECTIVE
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 deoxycholic 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 surrounding healthy mucosa. AR were found in all samples from both neoplastic and non neoplastic surrounding 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.


CONCLUSIONS
In cancerous large bowel mucosa, androgen receptors show altered binding characteristics. 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.
Berta
L
L
Department of Clinical Pathophysiology, University of Turin, Turin, Italy.
Fronticelli Baldelli
C
C
Fazzari
A
A
Radice
E
E
Bargoni
A
A
Frairia
R
R
Gaetini
A
A
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001647:Bile Acids and Salts / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism*; D004032:Diet / Q000009:adverse effects; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*
D001647:Bile Acids and Salts; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D013196:Dihydrotestosterone