From the extracts of enzyme-or acid hydrolysed pregnancy urine and urine of newborn infants a new oestrogen metabolite has been isolated.On the basis of the physical and chemical characteristics of this compound it is concluded that it is identical with 15\g=a\-hydroxy-oestriol(oestra\x=req-\ 1 , 3 , 5 ( 1 0 ) -t r i e n e -3 , 1 5 \ g = a \ , 1 6 \ g = a \ , 1 7 \ g = b \ -t e t r o l ) .It has been reported from this laboratory that one of the quantitatively most important metabolites of radioactive 17/5-oestradiol injected to malformed infants is an oestrogenic tetrol. It has been suggested that this compound is identical with 15a-hydroxy-oestriol, or possibly with 18-hydroxy-oestriol (Hagcn et al. 1965). Continued studies revealed that this compound is a normal constituent of pregnancy urine, of the urine of newborn infants and meconium 1 Ford Foundation Fellow in Reproductive Endocrinology. Present address:

Oestrone-6,7-3H-glucosiduronate-14C (OE1-3H-Gl-14C) has been prepared biosynthetically and its metabolism studied in two cases of therapeutic abortion following the administration of the tracer at laparotomy into the umbilical vein. The bulk of the radioactive material recovered was in the foetus and placenta; only small amounts were present in the urine of the mother. Minute quantities of the radioactive material recovered from any of these sources were in an unconjugated form. Following reduction with KBH4 of the extract of the foetal liver oestriol-3-glucosiduronate (OE3-3Gl) was isolated from this source with the same isotopic ratio as that of the injected material. Following hydrolysis with β-glucuronidase, 3H-labelled oestrone, 17β-oestradiol and oestriol were isolated in a radiochemically homogeneous form from the foetal liver and from the urine of the mother, and oestrone and 17β-oestradiol from the placenta. From the urine of the mothers OE1-3H-Gl-14C was also isolated. It exhibited the same isotopic ratio as the injected material. Following the intravenous infusion to two women at midpregnancy of a combination of 3H-labelled OE1-Gl and 14C-labelled oestrone sulphate (OE1-S), the tracer administered as OE1-Gl was eliminated in the urine far more rapidly than that infused in the form of OE1-S. It is concluded that at midpregnancy a) the foetus is capable of metabolizing OE1-Gl without any preceding hydrolysis, b) the placenta exhibits no β-glucuronidase activity, c) only a limited amount of OE1-Gl is transferred from the foeto-placental circulation to the mother and exclusively in an unchanged form, and d) OE1-Gl is eliminated from the maternal circulation much more rapidly than OE1-S.

Pregnant rats were deprived of paradoxical sleep for 3 days starting on the 18th gestational day. The condition of PS-D was imposed by confinement on a small platform surrounded by water or by daily injections of clomipramine. Four hours before the killing rats received a s.c. injection of [3H]-thymidine. The amount of radioactive DNA determined by autoradiography in several regions of fetal brain was found to be markedly increased under both experimental conditions in comparison with the control fetal brain. Considerably more limited effects were observed in kidney. Comparable changes of lower magnitude were obtained by comparing the specific radioactivity of DNA samples purified by chlorophorm extraction and digestion with RNase and proteinase K. The results fully confirm our previous data obtained under similar experimental conditions but based on the analysis of an acid-washed DNA fraction.