These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Indanyl analogs of diethylstilbestrol: differential interaction with prostaglandin H synthase.
    Author: Degen GH, Metzler M.
    Journal: Carcinogenesis; 1989 May; 10(5):839-45. PubMed ID: 2495865.
    Abstract:
    The prostaglandin H synthase (PHS)-catalyzed metabolism of indenestrol A (IA), indenestrol B (IB) and indanestrol (I) and the effects of these compounds on PHS were studied in incubations with ram seminal vesicle microsomes (RSVM) by means of arachidonic acid (20:4)-dependent oxygen consumption and by HPLC analysis of parent compound conversion as well as UV spectroscopy. IA and I were metabolized by PHS via co-oxidation. By analogy with diethylstilbestrol (DES) they stimulated PHS cyclo-oxygenase dose-dependently and became inhibitory at higher concentrations. Cyclo-oxygenase activity determined at 20:4 concentrations ranging from 10 to 70 microM revealed an antioxidant-type of inhibition for IA with IC50 values ranging from 30 to 150 microM. IB, on the other hand, displayed an indomethacin-like type of PHS inhibition with an IC50 value of 20 microM not dependent upon 20:4 concentration which was consistent with the observation that IB inhibited the co-oxidation of DES when initiated with 20:4 but not with hydrogen peroxide. Recovery of IB was incomplete in extracts from incubations with native PHS, but the reaction was neither 20:4 dependent nor inhibited by indomethacin or catalase; it was partially inhibited by eicosatetraynoic acid (ETYA) or by butylhydroxyanisol (BHA). This may indicate affinity of IB for the enzyme protein and conversion of IB other than by a co-oxidation mechanism. UV spectroscopy revealed the formation of a p-quinoid intermediate in incubations with IA, but not with IB or I. The IA-quinone was synthesized and reacted with nucleophiles such as water, methanol, ethanol and mercaptoethanol to adducts which were further characterized by gas chromatography/mass spectrometry. Our data indicate that indanyl derivatives of DES interact differently with PHS and thus could provide a useful tool for future studies on the mechanism of action of tumorigenic stilbene estrogens as well as on the elucidation of the role of PHS-mediated metabolism in their toxic action.
    [Abstract] [Full Text] [Related] [New Search]