Expression of 3beta-hydroxysteroid dehydrogenase-5,4-en isomerase activity by infiltrating ductal human breast carcinoma in vitro.
In order to determine whether human mammary tumors could contribute to progesterone synthesis from pregnenolone in breast cancer patients, homogenates of infiltrating ductal primary breast tumors at different stages of malignancy (Stages II and III) obtained from pre- and post-menopausal patients (n = 7, age 37-66 years) were incubated with [7n-3H]pregnenolone as substrate. Controls were heated homogenates instead of fresh homogenates. With the use of reverse-isotope dilution analysis, [3H]progesterone was isolated and characterized. No such metabolite was evident in the control incubations of heat-denatured enzymes. The extent of enzymic conversion varied from 0.02 to 4.0%. The results reveal that activity of 3beta-hydroxysteroid dehydrogenase-5,4-en isomerase that metabolizes pregnenolone to progesterone can be identified with the viable homogenates. It is suggested that there exists a potential for substantial progesterone synthesis in vivo. This conversion may be of considerable clinical, therapeutic, and pathophysiological significance in the patient with breast cancer. The biological impact of this conversion should be a high priority research objective.
Gunasegaram
R
R
University Department of Obstetrics & Gynaecology, National University Hospital, Singapore, Republic of Singapore.
Peh
K L
KL
Loganath
A
A
Ratnam
S S
SS
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D011374:Progesterone / Q000032:analysis* / Q000096:biosynthesis*
D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases