STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN.

1967 ◽  
Vol 55 (3) ◽  
pp. 401-414 ◽  
Author(s):  
S. Dell'Acqua ◽  
S. Mancuso ◽  
G. Eriksson ◽  
J. L. Ruse ◽  
S. Solomon ◽  
...  

ABSTRACT 16α-Hydroxy-dehydroepiandrosterone-7α-3H (16αHO-DHA), 16α-hydroxy-androstenedione-4-14C (16αHO-A) and 16α-hydroxy-testosterone-4-14C (16αHO-T) were synthesized. Human placentas were perfused in situ at midpregnancy with these steroids and the radioactive material recovered from the placentas and perfusates was analysed. In order to compare the aromatisation of 16α-hydroxylated and 16-desoxy precursors, in a second series of perfusions 16αHO-DHA was combined with differently labelled dehydroepiandrosterone (DHA) and 16αHO-T with testosterone (T). Following the perfusion of 16αHO-DHA, both 16αHO-A and oestriol (OE3) were isolated from the placentas and perfusates. No labelled androst-5-ene-3β,16α,17β-triol (Δ5-TRIOL) or 16αHO-T was detected in these sources. When 16αHO-A or 16αHO-T was perfused, OE3 was isolated from the placenta and perfusates. However, there was no interconversion between 16αHO-A and 16αHO-T. No oestrogenic ring D ketols were found in the placentas and perfusates in any of the experiments. The extent of aromatisation (judged from the amount of oestrogen isolated from the placenta and perfusate) was approximately the same following the perfusion of 16αHO-DHA, 16αHO-A, DHA and T, but was much lower when 16αHO-T was perfused. The low degree of aromatisation of 16αHO-T was associated with the presence of large amounts of unchanged 16αHO-T in the placentas as well as in the perfusates. The transfer of 16αHO-T to the maternal compartment was also much lower than that of the other precursors studied. It is concluded that the placental transfer and aromatisation of 16αHO-T is much lower than those of other oestrogen precursors. This condition might lead to the accumulation of this compound in the placenta. The placental metabolism of Δ5-TRIOL and 16αHO-DHA follow separate pathways with no interconversion until the stage of aromatisation, or possibly 19-hydroxylation.

1964 ◽  
Vol 45 (4) ◽  
pp. 535-559 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT In 15 cases of therapeutic abortion by laparotomy the placenta was disconnected from the foetus and perfused in situ with tracer amounts of radioactive dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), androst-4-ene-3,17-dione (A), testosterone (T) and 17β-oestradiol (OE2). Analysis of the placentas, perfusates and urine samples revealed an extensive aromatisation of DHA, A and T; more than 70% of the radioactive material recovered was phenolic, and at least 80 % of this phenolic material was identified as oestrone (OE1), 17β-oestradiol (OE2) and oestriol (OE3), the latter being detected only in the urine. Comparative studies indicated that A and T were aromatised somewhat better than DHA and that all three unconjugated steroids were aromatised to a much greater extent than DHAS. Radioactive OE1 and OE2 were isolated and identified in the placentas and perfusates, but no OE3, epimeric oestriols, or ring D ketols could be detected in these sources, not even when human chorionic gonadotrophin (HCG) was added to the blood prior to perfusion. Lack of placental 16-hydroxylation was also apparent when OE2 was perfused. Regardless of the precursor perfused, there was three times more OE2 than OE1 in the placenta and three times more OE1 than OE2 in the perfusate. This was also the case following perfusion with OE2. The results are interpreted as suggesting the existence in the pregnant human of a placental »barrier« limiting the passage of circulating androgen. The barrier consists of a) limited ability to transfer directly DHAS and b) an enzymic mechanism resulting in the rapid and extensive aromatisation of the important androgens DHA, A and T.


1961 ◽  
Vol 38 (4) ◽  
pp. 545-562 ◽  
Author(s):  
L. Kecskés ◽  
F. Mutschler ◽  
I. Glós ◽  
E. Thán ◽  
I. Farkas ◽  
...  

ABSTRACT 1. An indirect paperchromatographic method is described for separating urinary oestrogens; this consists of the following steps: acidic hydrolysis, extraction with ether, dissociation of phenol-fractions with partition between the solvents. Previous purification of phenol fraction with the aid of paperchromatography. The elution of oestrogen containing fractions is followed by acetylation. Oestrogen acetate is isolated by re-chromatography. The chromatogram was developed after hydrolysis of the oestrogens 'in situ' on the paper. The quantity of oestrogens was determined indirectly, by means of an iron-reaction, after the elution of the iron content of the oestrogen spot, which was developed by the Jellinek-reaction. 2. The method described above is satisfactory for determining urinary oestrogen, 17β-oestradiol and oestriol, but could include 16-epioestriol and other oestrogenic metabolites. 3. The sensitivity of the method is 1.3–1.6 μg/24 hours. 4. The quantitative and qualitative determination of urinary oestrogens with the above mentioned method was performed in 50 pregnant and 9 non pregnant women, and also in 2 patients with granulosa cell tumour.


1972 ◽  
Vol 70 (1) ◽  
pp. 132-142 ◽  
Author(s):  
U. Goebelsmann ◽  
J. M. Roberts ◽  
R. B. Jaffe

ABSTRACT Four human placentas were perfused in situ at midpregnancy, two with biosynthetically prepared 3H-oestriol-16-glucosiduronate-14C (OE3-16Gl) and two with 3H-oestriol-3-sulphate-16-glucosiduronate (OE3-3S,16Gl). The radioactive material recovered from the placentas, perfusates and maternal urine was quantitated and identified. Only 0.8 to 3.7% of the labelled material administered was recovered from urine specimens; the bulk of the labelled material perfused was found in the extracts of placentas and perfusates. The double-labelled material isolated from the three sources following perfusion with 3H-OE3-16Gl-14C was identified as OE3-16Gl. The 3H/14C ratios measured in these fractions were virtually identical with those of the tracers perfused. Following perfusion with 3H-OE3-3S,16Gl, three-fourths of the 3H-labelled material recovered from the urine was identified as OE3-3S,16Gl and a small but significant portion of the tritiated material extracted from the placentas and perfusates was shown to be 3H-OE3-16Gl. No significant quantities of unconjugated labelled material could be detected in any of the four placental perfusions. The data presented provide conclusive evidence that both OE3-16Gl and OE3-3S,16Gl are transferred across the placenta in situ without previous hydrolysis. The placenta in vivo is capable of converting some OE3-3S,16Gl to OE3-16Gl. The latter conjugate remains unhydrolysed.


1968 ◽  
Vol 59 (3) ◽  
pp. 426-432 ◽  
Author(s):  
U. Goebelsmann ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Two human placentas were perfused in situ at midpregnancy with a combination of oestriol-15-3H-3-glucosiduronate (OE3-3Gl) and oestriol-16-14C-16-glucosiduronate (OE3-16Gl) and the radioactive material recovered from the placentas, perfusates and urine specimens was analysed. Only 1 to 2 per cent of the tracers administered was recovered from the urine; the bulk of the administered material was found in the perfusates and placentas. Under the experimental conditions used, no evidence for the metabolism of the two conjugates was found. The OE33Gl isolated from the three sources contained only 3H-label, and the OE3-16Gl only 14C-label. Whereas the evidence indicating the placental transfer of OE3-16Gl in an unchanged form is circumstantial, conclusive evidence is presented that OE3-3Gl is transferred across the placenta without hydrolysis.


1964 ◽  
Vol 45 (2) ◽  
pp. 297-320 ◽  
Author(s):  
R. C. Haynes ◽  
G. Mikhail ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Five normal previable foetuses were perfused with tracer amounts of oestradiol-4-14C and the metabolism of the compound was investigated. This study was completed by 3 experiments in which the oestradiol-4-14C was introduced in situ into the intact foeto-placental unit via the umbilical circulation. More than 80 per cent of the radioactive material present in the various foetal organs in both types of experiments was in a conjugated form. In contrast, in the placentas, less than 10 per cent of the total radioactivity present was in a conjugated form. The bulk of the radioactive material present in the foetal tissues was identified as oestradiol 3-sulphate and oestrone sulphate. In addition, two minor fractions were detected in the perfused foetuses, one of which behaved in countercurrent distribution studies as »glucosiduronates«; the other resembled »sulphates«. The oestrogen moiety of these two fractions was neither oestradiol nor oestrone, but it appeared to be a complex mixture. Although some radioactive material was found which closely resembled oestriol, it was not possible to detect oestriol with certainty. No glucosiduronate-like material was found in the foetal tissues following the injection of oestradiol-4-14C into the intact foeto-placental unit. Also the quantity of the »sulphate-like« material different from oestradioland oestrone sulphates was greatly reduced: A number of unconjugated metabolites were also detected, among which oestrone was identified. A perfusion experiment with an anencephalic foetus indicated that this foetus was capable of forming conjugated metabolites from oestradiol-4-14C. The results obtained do not favour the view that oestriol is a major and instantaneously formed foetal metabolite of oestradiol. On the other hand, they lend additional support to the concept that oestrogens reaching the foetus are extensively sulphurylated by the foetus and that these oestrogen sulphates are hydrolysed by the placenta before transfer of the oestrogen moiety to the maternal circulation.


1965 ◽  
Vol 48 (3) ◽  
pp. 413-422 ◽  
Author(s):  
R. Jaffea ◽  
R. Pionb ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Using a variety of experimental techniques, including perfusion of placentas in situ, injection into the intact foeto-placental unit via the umbilical vein, as well as long-term administration into the amniotic sac or antecubital vein of the mother, very little if any oestrone, 17β-oestradiol- or oestriol-like radioactive material could be detected in the placenta, foetal tissues and urine of the mother following the administration of labelled progesterone. The results are interpreted as supporting the concept that progesterone is not a significant precursor of placental oestrogens.


Author(s):  
J. I. Bennetch

In a recent study of the superplastic forming (SPF) behavior of certain Al-Li-X alloys, the relative misorientation between adjacent (sub)grains proved to be an important parameter. It is well established that the most accurate way to determine misorientation across boundaries is by Kikuchi line analysis. However, the SPF study required the characterization of a large number of (sub)grains in each sample to be statistically meaningful, a very time-consuming task even for comparatively rapid Kikuchi analytical techniques.In order to circumvent this problem, an alternate, even more rapid in-situ Kikuchi technique was devised, eliminating the need for the developing of negatives and any subsequent measurements on photographic plates. All that is required is a double tilt low backlash goniometer capable of tilting ± 45° in one axis and ± 30° in the other axis. The procedure is as follows. While viewing the microscope screen, one merely tilts the specimen until a standard recognizable reference Kikuchi pattern is centered, making sure, at the same time, that the focused electron beam remains on the (sub)grain in question.


1965 ◽  
Vol 49 (2) ◽  
pp. 248-261 ◽  
Author(s):  
S. Mancuso ◽  
Francesca P. Mancuso ◽  
K.-G. Tillinger ◽  
E. Diczfalusy

ABSTRACT Two amenorrhoeic women were given a course of 10 injections of human menopausal gonadotrophin (HMG) in daily doses corresponding to 260 IU of follicle stimulating hormone (FSH) activity and 165 IU of interstitial cell stimulating hormone (ICSH) activity. In both patients an extensive ovarian stimulation was observed as indicated by the greatly increased urinary excretion of oestrone, 17β-oestradiol and oestriol. When HMG-treatment was followed subsequently by the administration of human chorionic gonadotrophin (HCG) for 5 days in a total dose of 18 000 and 30 000 IU, respectively, functional corpus luteum tissue was formed in both patients as evidenced by a huge rise in urinary pregnane-3α,20α-diol excretion and by the secretory transformation of a previously atrophic endometrium. At the approximate height of the follicular phase tracer doses of 3H-labelled dehydroepiandrosterone sulphate (DHAS) and 14C-labelled dehydroepiandrosterone (DHA) were administered to both patients in the form of a continuous intravenous infusion of 10 hours' duration. Infusion of the same dose was repeated under identical experimental conditions at the approximate height of the luteal phase. In both patients, very little radioactive material was associated with oestrone and 17β-oestradiol and none with oestriol isolated from 96-hours' urine specimens obtained at both phases of ovarian stimulation. It is concluded that — in contradistinction to the situation in pregnant women — circulating DHAS is not a significant precursor of urinary oestrogens in non-pregnant women.


1970 ◽  
Vol 65 (1) ◽  
pp. 69-83 ◽  
Author(s):  
H. Vokal ◽  
D. F. Archer ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT The following steroids, [7α-3H]5-androstene-3β,16α,17β-triol and [4-14C] 5-androstene-3β,16β,17β-triol were biosynthesized and their metabolism was studied in two subjects at midgestation, following placental perfusion in situ. Among the metabolites isolated in a radiochemically homogeneous form, exclusively 3H-labelled 16α,17β-dihydroxy-4-androsten-3-one was isolated from the extracts of placentas and perfusates. Exclusively 14C-labelled 16β,17β-dihydroxy-4-androsten-3-one was isolated from the placentas and perfusates and 16-epioestriol (1,3,5(10)-oestratriene-3,16β,17β-triol) from the placentas, perfusates and urine specimens. The following compounds contained both 3H and 14C-label: oestriol (placentas and urine specimens) and 5β-androstane-3α,16α,17β-triol (urine specimens). The 3H/14C-ratio of oestriol isolated from the urine specimens was much lower than that of urinary 5β-androstane-3α,16α,17β-triol, or that of the oestriol isolated from the placentas. The 3H/14C-ratio of the oestriol isolated from the urine 2–4 days following the perfusion was lower than that of the perfused material. It is concluded that a considerable amount of the 16-epioestriol secreted by the placenta is gradually converted to oestriol by the maternal organism. A limited conversion occurs also in the placenta.


2020 ◽  
Vol 98 (3) ◽  
pp. 178-184
Author(s):  
T. V. Chernyakova ◽  
A. Yu. Brezhnev ◽  
I. R. Gazizova ◽  
A. V. Kuroyedov ◽  
A. V. Seleznev

In the review we have integrated all up-to-date knowledge concerning clinical course and treatment of glaucoma among pregnant women to help specialists choose a proper policy of treatment for such a complicated group of patients. Glaucoma is a chronic progressive disease. It rarely occurs among childbearing aged women. Nevertheless the probability to manage pregnant patients having glaucoma has been recently increasing. The situation is complicated by the fact that there are no recommendations on how to treat glaucoma among pregnant women. As we know, eye pressure is progressively going down from the first to the third trimester, so we often have to correct hypotensive therapy. Besides, it is necessary to take into account the effect of applied medicines on mother health and evaluate possible teratogenic complications for a fetus. The only medicine against glaucoma which belongs to category B according to FDA classification is brimonidine. Medicines of the other groups should be prescribed with care. Laser treatment or surgery may also be a relevant decision when monitoring patients who are planning pregnancy or just bearing a child. Such treatment should be also accompanied by medicines.


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