PARAENDOCRINE BEHAVIOUR OF HUMAN BREAST CARCINOMA: IN VITRO TRANSFORMATION OF STEROIDS TO PHYSIOLOGICALLY ACTIVE HORMONES

Abstract

SUMMARY Conversion in vitro of [4-14C]dehydroepiandrosterone and [4-14C]pregnenolone to Δ4-3-ketosteroids has demonstrated the occurrence of an isomerasedehydrogenase system in human breast carcinoma tissue. Aromatisation of [4-14C]testosterone to oestriol, via 16α-hydroxytestosterone, also occurred, thus demonstrating for the first time a paraendocrine activity associated with steroid hormone production. A major metabolite of dehydroepiandrosterone was identified as androst-5-ene-3β, 16α, 17β-triol which may be an intermediate in the 'direct' pathway to oestriol. Steroid sulphatase activity was detected in homogenates of breast carcinoma tissue. This finding, and the previously demonstrated occurrence of steroid sulphokinases in the soluble fraction, suggest that sulphated forms of the steroid may act as intermediates in some of the transformations described. These observations can possibly explain previous unaccountable reports on the metabolism of steroids administered to oophorectomized and adrenalectomized patients with breast carcinoma. The formation of oestriol and androst-5-ene-3β,16α,17β-triol by the carcinoma tissue may offer an explanation for the significant elevation of oestriol and the lowered dehydroepiandrosterone concentrations in the urine of postmenopausal women with breast cancer (Marmorston, 1966).