STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN 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.

1968 ◽  
Vol 58 (3) ◽  
pp. 377-395 ◽  
Author(s):  
J. W. Reynolds ◽  
S. Mancuso ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT 3β,17β-Dihydroxy-androst-5-en-16-one-4-14C (16-oxo-Δ5-DIOL) has been biosynthesized and four placentas were perfused in situ at midpregnancy with tracer amounts of this compound in combination with dehydroepiandrosterone-7α-3H. Exclusively 3H-labelled oestrone (OE1) and 17β-oestradiol (OE2) and exclusively 14C-labelled 17β-hydroxy-androst-4-ene-3,16-dione (16-oxo-T), 3,17β-dihydroxy-oestra-1,3,5(10)-trien-16-one (16-oxo-OE2) and oestra-1,3,5(10)-triene-3,16β,17β-triol (16-epi-OE3) were isolated in a radiochemically homogeneous form from the placentas as well as from the perfusates. In addition, 16α,17β-dihydroxy-androst-4-en-3-one (16α-HO-T) and oestriol (OE3) were isolated from the placentas, but not from the perfusates. Among the 16-substituted compounds isolated, 16-oxo-OE2 was the quantitatively most important one in the placentas and 16-oxo-T in the perfusates. Crystallisation with authentic carrier indicated the absence of any androst-5-ene-3β,16α,17β-triol (Δ5-TRIOL), 3β,16α-dihydroxy-androst-5-en-17-one (16α-HO-DHA), 16β,17β-dihydroxy-androst-4-en-3-one (16β-HO-T) and 3,16α-dihydroxy-oestra-1,3,5(10)-trien-17-one (16α-HO-OE1) in the combined extracts of placentas and perfusates. In addition, chromatographic evidence indicated the lack of androst-5-ene-3β,16β,17β-triol (16-epi-Δ5-TRIOL) and 16α-hydroxy-androst-4-en-3,17-dione (16α-HO-A) in these sources. From the urine specimens 3H-labelled OE1, OE2 and 16α-HO-OE1 and both 3H and 14C-labelled 16-oxo-OE2, OE3 and 16-epi-OE3 were isolated. The 3H/14C ratio of urinary 16-oxo-OE2 was significantly higher than that of OE3 whereas the isotopic ratio of urinary 16-epi-OE3 was significantly lower than those of 16-oxo-OE2 and OE3. A concept is presented describing the formation mechanism of 16-oxo-OE2. OE3 and 16-epi-OE3 in the placental compartment of the human foeto-placental unit at midpregnancy.


1971 ◽  
Vol 66 (4) ◽  
pp. 637-647 ◽  
Author(s):  
J. Schwers ◽  
T. Vancrombreucq ◽  
M. Govaerts ◽  
G. Eriksson ◽  
E. Diczfalusy

ABSTRACT Two midgestation placentas were perfused in situ with a combination of [7α-3H] dehydroepiandrosterone sulphate and [4-14C] oestrone sulphate and metabolites were isolated from the placentas, perfusates and maternal urine specimens. Approximately 70 per cent of the perfused radioactive material was recovered from these three sources. The bulk of the administered radioactive material was recovered in an unchanged form from the perfusates; some 2–4 per cent was excreted in the urine and less than 0.5% was found in the placentas. The tritium to carbon-14 ratio of the unconjugated material isolated from the perfusates and placentas was higher, and that of the conjugated material recovered from the same sources was lower than the ratio of the administered material. In addition, more tritium than carbon-14 labelled material was present in the urine. Approximately 2 per cent of the perfused dehydroepiandrosterone sulphate was recovered in the form of phenolic steroids, mostly from the urine. From this source double labelled oestrone, oestriol, 16α-hydroxy-oestrone and 16-epioestriol were isolated. The tritium to carbon-14 ratio of all oestrogens isolated from the urine was higher than that of the perfused material. From the urine specimens 10 to 15 times more double labelled oestriol than oestrone was isolated.


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.


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.


1967 ◽  
Vol 55 (2) ◽  
pp. 263-277 ◽  
Author(s):  
E. Lamb ◽  
S. Mancuso ◽  
S. Dell' Acqua ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Dehydroepiandrosterone sulphate (DHAS) labelled with 3H and dehydroepiandrosterone (DHA) labelled with 14C were simultaneously administered into the arterial supply of four placentas perfused in situ immediately following the removal of the foetus at midpregnancy. From the perfused placentas testosterone (T), androstenedione (A), oestrone (OE1) and 17β-oestradiol (OE2) derived from the metabolism of both DHA and DHAS were isolated in a radiochemically homogeneous form. In addition DHA derived from DHAS was isolated. No labelled 19-hydroxy-androst-4-ene-3,17-dione, or 3β,19-dihydroxy-androst-5-en-17-one was detected. From the perfusates the same steroids were isolated as from the placentas. They contained so small amounts of 3H that their radiochemical homogeneity could be established only on the basis of the 14C label. The 3H/14C ratio of the A isolated from each placenta was higher than that of DHA and OE1 isolated from the same source, indicating a higher contribution of DHAS to A than to DHA or OE1 However, no conjugated or unconjugated intermediates between DHAS and A other than DHA were detected. One possible explanation for the differences in isotope ratios based on the existence of two hypothetical placental compartments, is discussed.


2021 ◽  
Vol 74 (3) ◽  
pp. 460-464
Author(s):  
Iryna M. Shcherbina ◽  
Iryna Yu. Plakhotna

The aim: To assess the condition of the vaginal ecosystem in pregnant women with BV. Materials and methods: The main group consisted of 60 pregnant women with BV in the II trimester. The bacterioscopic examination, of vaginal smears was carried out. DNA diagnostics of the microbial spectrum of vaginal contents was performed. Bacteria with biofilm were visualized by fluorescence hybridization in situ. Results: Biofilms were found in 25 women (41.65%) of the main group, the main component of which was bacteria belonging to the Gardnerella cluster at a concentration of 7.9 ± 0.13 log CFU/ g. Atopobium vagine cluster bacteria gave positive hybridization signals in more than half of the patients and amounted to 6.8 ± 0.15 lg CFU / g. In addition, Snethia spp. was determined as a part of the biofilm at a concentration of 5.8 ± 0.3 lg CFU / g. Conclusions: Thus, the use of the proposed treatment regimen for women with vaginal dysbiosis led to the elimination of pathogenic and conditionally pathogenic microflora. However, the effectiveness of treatment in 5 cases was lower than expected, which indicates the emergence of bacterial resistance.


2000 ◽  
Vol 81 (11) ◽  
pp. 2625-2633 ◽  
Author(s):  
Signy Bendiksen ◽  
Ole Petter Rekvig ◽  
Marijke Van Ghelue ◽  
Ugo Moens

The ubiquitous human polyomaviruses BK (BKV) and JC (JCV) persist with no adverse effects in immunocompetent individuals. Virus-induced pathogenesis has been linked to virus reactivation during impaired immune conditions. Previous studies have shown a significant difference between the VP1 DNA sequences of JCV obtained from control urine samples and those in progressive multifocal leukoencephalopathy brain samples. This difference could not be detected when comparing normal control urinary JCV DNA with DNA sequences from chronic progressive multiple sclerosis patients. Since BKV and JCV are readily activated in systemic lupus erythematosus (SLE) patients, the presence of specific strains, related to VP1 DNA sequences, was investigated in these patients. VP1 DNA sequences in 100 urine samples from 21 SLE patients and 75 urine samples from 75 healthy pregnant women were analysed and compared to previously reported sequences. The results show that the VP1 sequence profiles of JCV and BKV excreted by SLE patients do not differ significantly from those excreted by immunocompetent individuals. The European JCV subtypes 1A or 1B were represented among all JCV-positive urine specimens, while BKV VP1 sequences showed complete, or almost complete, identity with the MM or JL strains. Different urine samples from the same patient collected over a 1 year period were predominantly stable. BKV VP1 DNA in urine specimens from healthy pregnant women was only detected during the third trimester of their pregnancy. These results argue against SLE-specific JCV and BKV strains and suggest reactivation of the viruses rather than recurrent re-infections of patients with SLE.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Jaime Salvador-Moysén ◽  
Yolanda Martínez-López ◽  
José M. Ramírez-Aranda ◽  
Marisela Aguilar-Durán ◽  
Alberto Terrones-González

There are analyzed some of the main aspects related to the causality of preeclampsia, privileging two types of models: the clinic model and the epidemiologic model, first one represented by the hypothesis of the reduced placental perfusion and the second one considering the epidemiologic findings related to the high levels of psychosocial stress and its association with preeclampsia. It is reasoned out the relevance of raising the causality of the disease from an interdisciplinary perspective, integrating the valuable information generated from both types, clinical and epidemiologic, and finally a tentative explanatory model of preeclampsia is proposed, the subclinical and sociocultural aspects that predispose and trigger the disease are emphasized making aspects to stand out: the importance of reduced placental perfusion as an indicator of individual risk, and the high levels of physiological stress, as a result of the unfavorable conditions of the psychosocial surroundings (indicator of population risk) of the pregnant women.


2019 ◽  
Vol 128 (12) ◽  
pp. 788-795
Author(s):  
Zoltan Kozinszky ◽  
AbelT. Altorjay ◽  
Andras Molnar ◽  
Tibor Nyári ◽  
Sandor G. Vari ◽  
...  

Abstract Aims The aim of our study was to assess the effect of glycemic control on placental vascularization in pregnancies complicated by type 1 diabetes mellitus (T1DM) and to compare dataset of optimal/suboptimal glycemic control to normal placental 3-dimensional power Doppler (3-DPD) indices in 2nd and 3rd trimester. Methods Placental vascularization of pregnant women was prospectively evaluated by 3-DPD ((vascularization-index (VI); flow-index (FI); vascularization-flow-index (VFI)) ultrasound technique. The normal pregnancies (n=214) were compared to those complicated by T1DM (n=53) with optimal (HbA1C≤6%;≤ 42 mmol/mol) and suboptimal (HbA1C>6%;>42 mmol/mol) glycemic control. Results Pregnancies complicated by T1DM expressed lower placental vascularization indices as compared with normal pregnancies (adjusted odds ratio (AOR) for VI:0.86; FI:0.94; VFI:0.76). Placental 3-DPD indices have a significant correlation with HbA1C and optimal glycemic control is associated with lower placental perfusion (AOR for VI:1.64; FI:1.13; VFI:2.34). Short-term adverse neonatal outcome was predicted by lower 3-DPD indices (AORVI:0.83, AORFI:0.93, AORVFI:0.66, p<0.05 for each index). Besides the glycemic control, the pregestational body mass index (BMI), had significant influences on placental perfusion. Conclusions VI displayed the best screening ability for suboptimal glycemic control with a sensitivity of 90.9%. The suboptimal glycemic control has a direct deteriorating effect on placental vasculature. Therefore the ultrasound examination could be an adjunct diagnostic modality for pregnant women with T1DM.


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