engleski

Influence of ethynodiol diacetate on the formation of A-homo-3-oxa-5-alpha-pregnane-4, 20-dione in female rats

Objective. To give more insight in the progesterone metabolism in rat after the treatment with the progestin ethynodiol diacetate. Methods. Urinary excretion of the metabolites of subcutaneously administered /4-14C/-progesterone was studied in female rats. After an acid hydrolysis and extraction of urine the metabolites were analysed by thin layer chromatography and by gas chromatography-mass spectrometry. Results. The most of radioactivity was excreted during the first 24 h, and total of 8.36 % has been recovered within four days. The excreted metabolites in urine were found as glucuronides and free steroids (80.72 %), and 19.28 % were determined as sulphates. Among detected metabolites, 5-alpha-pregnane-3, 20-dione, 3-alpha-hydroxy-5-alpha-pregnan-20-one and A-homo-3-oxa-5-alpha-pregnane- 4, 20-dione were determined in the urinary extracts. The last one has not been identified before in rat urine. Conclusions. Consecutive injections of progestin ethynodiol diacetate (6 mg/kg b.w. daily) to adult female rats during 10 days (short-term treatment), or during 70 days (long-term treatment), starting on the 21st day of life, caused significant differences in the amounts of excreted 3-alpha-hydroxy-5-alpha-pregnan-20-one and A-homo-3-oxa-5-alpha-pregnane-4, 20-dione. Significant increase in weights of pituitary, liver and kidneys were noted in rats treated with ethynodiol diacetate. The short-term treatment caused an increase, while after the long-term treatment a decrease of the ovarian weight was observed.

progesterone metabolites; rat; urine; ethynodiol diacetate; gas chromatography - mass spectrometry

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