Progesterone metabolism in T47Dco human breast cancer cells--I. 5 alpha-pregnan-3 beta,6 alpha-diol-20-one is the secreted product.
Progesterone is a major hormone controlling normal breast development and function. In breast cancer, progesterone may be involved in tumor growth regulation, and the concentration of the intracellular receptor proteins for progesterone are used to distinguish hormone dependent from autonomous tumors. We have been studying the cytoplasmic and nuclear distribution of progesterone receptors after progesterone treatment of cultured T47Dco human breast cancer cells. Anomalous behavior of the receptors, when progesterone was compared to synthetic progestins, suggested that progesterone was being rapidly metabolized by the cells. We have now studied this metabolism in detail. When progesterone is added to medium of proliferating cells, it disappears with a half life of 2-4 h. A single metabolite (P-metabolite) is quantitatively released into the medium, but its release is delayed 10-14 h. The quantitative conversion of progesterone to P-metabolite was confirmed using two independent methods: gas chromatography with internal standards, and 14C-radioisotope measurements. We have used gas chromatography, gas chromatography/mass spectrometry, thin layer chromatography and nuclear magnetic resonance to identify the final metabolic product released into the medium as 5 alpha-pregnan-3 beta,6 alpha-diol-20-one.
D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011278:Pregnanes; D011280:Pregnanolone / Q000031:analogs & derivatives* / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*
D011278:Pregnanes; D011374:Progesterone; C051190:pregnan-3,6-diol-20-one; D011280:Pregnanolone