STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1964 ◽  
Vol 45 (4) ◽  
pp. 560-575 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Tracer amounts of dehydroepiandrosterone-4-14C (DHA-4-14C) and dehydroepiandrosterone-7α-3H sulphate (DHAS-7α3H) were injected simultaneously into a uterine artery in two patients twelve to fifteen minutes prior to therapeutic interruption of pregnancy at laparotomy and the amniotic fluid, foetuses, placentas and urine samples were analysed for radioactive material. No radioactivity was found in the amniotic fluid. Regardless of the tracer administered, approximately 80 per cent of the radioactive material recovered from the placentas was in an unconjugated (free) form, whereas more than 80 per cent of the radioactivity present in the foetuses was in a conjugated form. More than 67 per cent of the total radioactive material in the two placentas and more than 87 per cent of that in the two foetuses was present as phenolic material. Approximately half of this phenolic material was identified as oestrone (OE1) and 17β-oestradiol (OE2). The 3H to 14C ratio of OE1 and OE2 isolated from the foetuses and urine specimens was lower than the ratio of the injected material. Corresponding 3H to 14C ratios in placental OE1 and OE2 were higher than those in foetal or urinary OE1 and OE2. Labelled oestriol (OE3) could be detected in the placentas, but not in the foetuses. However, a 16-hydroxylated phenolic intermediate (probably 16α-hydroxyoestrone) was found in one foetus studied. The results indicate that the DHA and DHAS of the maternal circulation can serve as direct precursors to placental OE2 and OE1 and as indirect precursors – via a foetal intermediate – to placental OE3. Both compounds reach the foetus mostly as phenolic material, the free form being a better precursor than the sulphate. It is suggested that – around midpregnancy at least – the human placenta functions as a barrier limiting the transfer to the foetus of androgens present in the maternal circulation.

1964 ◽  
Vol 46 (4) ◽  
pp. 525-543 ◽  
Author(s):  
R. Wilson ◽  
G. Eriksson ◽  
E. Diczfalusy

ABSTRACT Oestriol-16-14C was administered intravenously to four pregnant women prior to sterilisation and surgical interruption of pregnancy and the quantity and nature of radioactive metabolites in the products of conception, systemic venous blood and urine were studied. Thirty minutes following the injection of the isotope, less than 0.5 per cent of the administered dose was found in the amniotic fluid, foetus and placenta. Approximately 40 per cent of the radioactive material recovered from the systemic venous blood withdrawn 10 to 30 minutes following injection was unconjugated (free) oestriol. Some 15 per cent of the circulating radioactive material was identified as oestriol-3-sulphate and almost 10 per cent behaved as oestriol-3-sulphate,16(17?)-glucosiduronate. Oestriol-16(17?)-glucosiduronate was also detected, but only in minute quantities (0.5 per cent of total). The rest of the circulating radioactive material was present as unidentified »polar conjugates«. Urine specimens collected over various intervals revealed a changing pattern of conjugation. Oestriol and oestriol-3-sulphate were present only in very small amounts in all specimens studied. The bulk of radioactive material was excreted as oestriol-16(17?)-glucosiduronate and as so-called »polar glucosiduronates« (consisting of di- and perhaps triglucosiduronates of oestriol), accompanied by small, but significant, amounts of oestriol-3-sulphate,16(17?)-glucosiduronate-like radioactive material. As time passed following injection of the isotope, the amount of »polar glucosiduronates« present in the urine increased markedly. This was associated with a corresponding decrease in the amount of oestriol-16(17?)-glucosiduronate. At least 99 per cent of the oestrogen moiety of the urinary radioactive material consisted of oestriol. The recovery of radioactivity from the urine, collected during 72 hours, was low, ranging from 41 to 47 per cent.


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.


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.


2000 ◽  
pp. 53-59 ◽  
Author(s):  
ML Raffin-Sanson ◽  
F Ferre ◽  
J Coste ◽  
C Oliver ◽  
D Cabrol ◽  
...  

OBJECTIVE: The human placenta normally expresses the pro-opiomelanocortin (POMC) gene. The pattern and secretory kinetics of POMC and/or POMC-derived peptides by the placenta during gestation is still debated. We recently demonstrated that full length POMC was a normal product of the human placenta. The aim of our study was to establish its normal secretory kinetics and to explore its physiological relevance. DESIGN: In a prospective, longitudinal study, thirty normal pregnant women had monthly measurements of plasma POMC. In a cross-sectional study of 128 healthy pregnant women, plasma POMC and human chorionic gonadotrophin (hCG) were concomitantly measured to assess their correlation. Finally, POMC levels were assessed in venous and arterial cord blood samples, in amniotic fluid and in retroplacental blood. METHODS: Plasma POMC was measured by a specific IRMA in unextracted blood or biological fluid. RESULTS: Plasma POMC became detectable by the 8th week of pregnancy and reached its maximum at around the 20th week, remaining stable thereafter. The relationship between POMC and gestation time (weeks) best fitted with a third degree polynomia curve. A significant negative correlation (P=0.01) was observed between plasma levels of POMC and hCG after adjustment for gestation time to take into account the dependence of both hormones on this parameter. POMC was not secreted into the fetal circulation at term, but was present in very high levels in amniotic fluid. The highest levels of POMC were present in the retroplacental blood where the values were 35 times higher than in maternal blood; by comparison, corticotrophin releasing hormone and ACTH values in this compartment were twice or equal to those in the maternal blood. CONCLUSION: Placental POMC secretion increases during the first half of pregnancy and reaches a plateau from the 20th week to delivery. The inverse correlation between POMC and hCG plasma levels, and very high POMC levels at the feto-maternal interface suggest a physiological role for this precursor during pregnancy.


1985 ◽  
Vol 54 (3) ◽  
pp. 577-583 ◽  
Author(s):  
D. Sklan ◽  
I. Shalit ◽  
N. Lasebnik ◽  
Z. Spirer ◽  
Y. Weisman

1. The proteins binding retinol, and retinol concentrations, were determined in amniotic fluid, placental cytosol and in the fetal and maternal circulation.2. In non-pregnant women, plasma retinol was almost exclusively found in a transthyretin-retinol-binding-protein complex whereas, in pregnant women, retinol-binding-protein-bound retinol was observed not complexed to transthyretin. This latter fraction increased in concentration with fetal age. These two fractions were the major retinol-protein complexes in amniotic fluid and their relative amounts changed with progress of gestation.3. In fetal blood both of these fractions were again found, with higher proportions of retinol-binding- protein-bound retinol in the umbilical artery than in the umbilical vein.


2000 ◽  
Vol 38 (1) ◽  
pp. 1-6
Author(s):  
Rachel N. Jones ◽  
M. Lynne Neale ◽  
Brian Beattie ◽  
Diana Westmoreland ◽  
Julie D. Fox

ABSTRACT Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world. We have designed and evaluated an assay that includes an internal control for amplification and detection of CMV DNA in amniotic fluid and neonatal urine samples. We present data on the use of this assay in the diagnosis of congenital CMV infection. A total of 145 amniotic and fetal fluid samples were examined by this assay; 83 were from healthy pregnant women and 62 were from women who were being investigated because of concerns over the pregnancy (diagnostic group). CMV DNA was detected in three amniotic fluid samples from the diagnostic group but was not detected in any samples taken from healthy pregnant women. Thirty-nine urine samples were obtained from 19 neonates with suspected congenital infection; CMV DNA was detected in urine from 6 of these patients. The assay provides useful information about CMV infection in the fetus and the neonate; when used in conjunction with other diagnostic tools it will enable mothers and obstetricians to make informed decisions about the management of pregnancies complicated by CMV infection.


1971 ◽  
Vol 66 (4) ◽  
pp. 653-665 ◽  
Author(s):  
G. Benagiano ◽  
M. Ermini ◽  
B. de la Torre ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Three midgestation placentas were perfused at laparotomy during fifteen minutes with tracer amounts of [1,2-3H] testosterone [35S] sulphate sodium salt, and metabolites present in the placentas, perfusates and maternal urine specimens were analyzed. Most of the radioactive material administered was present in the placentas and perfusates; approximately 2% of it was recovered from the urine. More than 99.5% of the radioactive material recovered from the placentas and the perfusates was in a water soluble (conjugated) form. No unconjugated testosterone was found in these sources. Radiochemically homogeneous [1,2-3H] testosterone [35S] sulphate was isolated from the placentas, perfusates and urine specimens collected during the first 24 hours of experiment. The isotopic ratio of the conjugate isolated from these sources was very similar to that of the perfused material. Seventy per cent of the double labelled radioactive material recovered from the Day 1 urine samples was radiochemically homogeneous testosterone sulphate. The relative amounts of testosterone sulphate present in the Day 2 and Day 3 urine specimens showed a gradual decrease. This decrease was associated with an increase in tritium to sulphur-35 ratio. From the pooled extracts of all urine specimens, small amounts of exclusively tritium labelled conjugated 5α-androsterone and 5β-androsterone were also isolated. No 17β-oestradiol 17-sulphate was detected in any of the sources studied. It is concluded that little, if any, testosterone sulphate is hydrolyzed by the midgestation human placenta, and that a considerable part of the testosterone sulphate secreted by the foetus is transferred across the placenta to the mother in an unchanged form. The major part of the transferred testosterone sulphate is excreted in the urine; a smaller part of it undergoes hydrolysis with a subsequent metabolism of the steroid moiety.


1966 ◽  
Vol 52 (4) ◽  
pp. 550-564 ◽  
Author(s):  
U. Goebelsmanna ◽  
N. Wiqvist ◽  
E. Diczfalusy ◽  
M. Levitzb ◽  
G. P. Condonc ◽  
...  

ABSTRACT Tracer amounts of 3H-labelled oestriol-3-sulphate (OE3-3S) and 14C-labelled oestriol-16-glucosiduronate (OE3-16GI) were administered intraamniotically to two women at midterm 24 hours prior to the interruption of gestation. The radioactive metabolites present in the urine of the mother, amniotic fluid, placenta and various foetal tissues were isolated and identified. Averaging the results of the two experiments, 89% of the administered radioactive material was recovered. Thirty-six per cent of the 3H- and 12% of the 14C-labelled material was recovered from the maternal urine collected during the 24 hours preceding the termination of pregnancy, and an additional 14% of the 3H- and 4% of the 14C-labelled material during the following 96 hours. Thirty-five per cent of the 3H- and 67% of the 14C-labelled material administered were recovered from the foetal tissues and placenta.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Carla Prezioso ◽  
Marijke Van Ghelue ◽  
Ugo Moens ◽  
Valeria Pietropaolo

Abstract Background Human polyomavirus 6 (HPyV6) and HPyV7 are two of the novel polyomaviruses that were originally detected in non-diseased skin. Serological studies have shown that these viruses are ubiquitous in the healthy adult population with seroprevalence up to 88% for HPyV6 and 72% for HPyV7. Both viruses are associated with pruritic skin eruption in immunocompromised patients, but a role with other diseases in immunoincompetent patients or malignancies has not been established. Methods PCR was used to determine the presence of HPyV6 and HPyV7 DNA in urine samples from systemic lupus erythematosus (n = 73), multiple sclerosis (n = 50), psoriasis vulgaris (n = 15), arthritic psoriasis (n = 15) and HIV-positive patients (n = 66). In addition, urine from pregnant women (n = 47) and healthy blood donors (n = 20) was investigated. Results HPyV6 DNA was detected in 21 (28.8%) of the urine specimens from SLE patients, in 6 (9.1%) of the urine samples from the HIV-positive cohort, and in 19 (40.4%) samples from pregnant women. HPyV7 DNA was only found in 6 (8.2%) of the urine specimens from SLE patients and in 4 (8.5%) samples from pregnant women. No HPyV6 and HPyV7 viruria was detected in the urine samples from the other patients. Conclusions HPyV6, and to a lesser extend HPyV7, viruria seems to be common in SLE and HIV-positive patients, and pregnant women. Whether these viruses are of clinical relevance in these patients is not known.


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.


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