Mechanisms of sex-steroid accumulation in the aetiology of human breast carcinoma: the role of intracellular sex hormone binding globulin.
In malignant breast tissue cytosols (n = 14), significantly high levels of oestradiol (E2), testosterone and 5a-dihydrotestosterone (DHT) and sex hormone binding globulin (SHBG) were found as compared to breast tissue cytosols from normal women (n = 12) (p less than 0.001 for all parameters measured). In serum from the same patients and normal control groups no differences in these hormones or SHBG were detected, nor was relationship between serological and cytosolic levels observed. In the cytosol of the malignant group there was a significant correlation between testosterone and DHT, r = 0.98, p less than 0.001. This was also the case in the cytosol of normal breast tissue, r = 0.97, p less than 0.001. No such correlation between the two androgens was observed in the sera of either group. We hypothesise that the malignant breast is able to regulate its own hormonal milieu and that the nearly 8 times higher levels of intracellular SHBG compared to those in normal breast cytosol may be one the factors responsible for this accumulation of sex-steroids. In addition, SHBG due to its higher affinity for androgens than for E2 may shift the balance in favour of free oestrogens in malignant breast tissue.
Iqbal
M J
MJ
Department of Surgery, Rayne Institute, Kings College School of Medicine and Dentistry, London, England.
Valyani
S H
SH
Roberts
J V
JV
D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol