Venning and Browne (1 to 7) have shown that sodium pregnanediol glucuronidate is excreted in urine of human pregnancy in concentrations which become increasingly higher as gestation approaches term. Although this demonstration has been repeatedly confirmed (8 to 16), relatively few workers have studied the precise levels and ranges of normal excretion, or have secured long-continued records of output in individual parturients. As a consequence, there has not been complete agreement concerning the quantitative aspects of normal excretion. We have accordingly studied the urines of a number of healthy women throughout pregnancy. In addition to corroborating the original findings of Venning and Browne, our studies have thrown light upon a number of points which have previously been in question, and have supplied data concerning excretion during multiple pregnancy.
METHODSTwenty-four hour volumes of urine were collected at weekly intervals from early pregnancy to the onset of labor. The specimens were delivered to the laboratory within an hour of the completion of their collection, and were then kept at 0 to 50 until their work-up, which in no instance was delayed longer than 15 hours.The work-up of the urines was carried out in accordance with Venning's modified method (3), except that 3.0 cc. of water were used for re-dissolving the first precipitates obtained from acetone. From the 24-hour collections, aliquots were selected which were expected to yield at least 15 mgm. of the glucuronidate. When the pure compound was added to pregnancy urines in this amount, recoveries were quantitative with the procedure employed. This did not justify the assumption that the recoveries of the pre-formed glucuronidate of such urines were also quantitative, since the addition of 15 mgm. of pure compound to urines containing no glucuronidateie., male or menopausal urine-resulted in recoveries of only about 85 per cent. Nevertheless, the yields of preformed compound from pregnancy urine were calculated 1Aided by a grant from the Penrose Fund of the The pregnanediol glucuronidate isolated during the systematic examinations of pregnancy urine was identified in every instance by a melting point determination, standardized to the above rate of heating. In general, the preparations obtained from urine of early and mid-pregnancy were relatively colorless crystals which rarely melted at temperatures lower than 2730 (corrected). Those obtained from urine of late pregnancy were brown and semicrystalline, and showed melting points 6 to 100 lower than that of the standard preparation. Although it was obvious that the impurities present in such samples caused over-estimates of the amounts of glucuronidate obtained, no correction was applied to the yields. However, preparations which gave melting points more than 100 lower than the standard were further purified before weighing.In conformity with previous reports, our results have been recorded in terms of free pregnanediol. Since our glucuronidate products were dried in vacuo before weighing, a...
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