Blood levels of progesterone and 15-keto-13,14-dihydro-prostaglandin F2alpha during the normal oestrous cycle and early pregnancy in heifers.
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Biomedical subjects
Publications and source records attributed to E Granström.
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Radioimmunoassays were developed for the main plasma and urinary metabolites of PGF2alpha in the human, viz., 15-keto-13,14-dihydro-PGF2alpha and 5alpha, 7alpha-dihydroxy-11-ketotetranorprosta-1,16-dioic acid. The methods allowed assay of unextracted samples and had a sensitivity of 5 pg and 2 pg, respectively. The assays were evaluated by comparison with mass spectrometric data. Normal levels of these metabolites were estimated in a number of subjects. Levels in plasma and urine of the metabolites were followed after injection or during infusion of PGF2alpha and during administration of various antiinflammatory drugs.
The metabolism of three analogues of PGF2alpha was studied in the Cynomolgus monkey and in the human, viz., 15-methyl-PGF2alpha, 16,16-dimethyl PGF2alpha, and 17-phenyl-18,19,20-trinor-PGF2alpha. The half-lives of the three compounds in the human circulation was considerably longer than that of PGF2alpha. The dehydrogenation of the secondary alcohol group at C-15 was completely blocked in the two first-mentioned compounds. These were degraded mainly by beta-oxidation, and their main metabolites, both in plasma and urine, were dinor-15-methyl-PGF2alpha and dinor-16,16-dimethyl-PFG2alpha, respectively. 17-Phenyl-18,19,20-trinor-PGF2alpha, finally, was metabolized to some extent by dehydrogenation at C-15, and also by reduction of the delta13 double bond and by beta-oxidation.
The levels of the major plasma metabolite of PGF2alpha, 15-keto-13,14-dihydro-PGF2alpha, were followed in peripheral venous plasma during the reproductive cycle in three species, viz., the ovine, bovine, and human species. In the sheep and cattle low levels were encountered during the major part of the estrous cycle. During the last days of the cycle high levels of the prostaglandin metabolite were found, coinciding with the decrease in progesterone production. The human menstrual cycle was characterized with respect to some plasma steroids and peptide hormones. The prostaglandin metabolite levels were low throughout the cycle, generally ranging between 30 and 70 pg/ml. No significant variation in the prostaglandin production could be seen during the menstrual cycle.
[9beta- -3H]-17-Phenyl-18,19,20-trinor-PGF2alpha was injected subcutaneously into female Cynomolgus monkeys and the structures of six products appearing in the urine were determined. The main urinary metabolites were the dinor- and tetranor-derivatives of 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha. Unchanged 17-phenyl-18,19,20-trinor-PGF2alpha was also identified among the urinary products, as well as its dinor- and tetranor-derivatives. Finally, the dinor-derivative of 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha was also found in urine. The same six products were also found in urine from human female subjects that had received 17-phenyl-18,19,20-trinor-PGF2alpha either subcutaneously or intravenously. Studies on the half-life of the compound in the circulation were also performed in human females. Two less polar metabolites in plasma were identified, viz. 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha and 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha.
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