STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1965 ◽  
Vol 48 (3) ◽  
pp. 413-422 ◽  
Author(s):  
R. Jaffea ◽  
R. Pionb ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Umbilical Vein ◽  
Radioactive Material ◽  
Experimental Techniques ◽  
Antecubital Vein ◽  
Term Administration

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.

STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1964 ◽  
Vol 45 (4) ◽  
pp. 576-599 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Specific Activity ◽  
Umbilical Vein ◽  
Radioactive Material ◽  
Placental Barrier ◽  
Therapeutic Abortion ◽  
Antecubital Vein

ABSTRACT In connection with therapeutic abortion, in two patients tracer amounts of dehydroepiandrosterone-4-14C sulphate (DHAS-4-14C) were injected into the umbilical vein and tracer amounts of dehydroepiandrosterone-7α-3H sulphate (DHAS-7α-3H) into an antecubital vein. The over-all aromatisation of the two labelled compounds in the presence of viable foetuses was studied by analysing the radioactive metabolites excreted in the urine during a period of 6 days. More than 25 per cent of the 3H-labelled metabolites and more than 75 per cent of the 14C-labelled metabolites recovered from the urine were phenolic in character. More than half of this phenolic radioactive material behaved as oestrone (OE1), 17β-oestradiol (OE2) and oestriol (OE3) when analysed by a modified Brown (1955) method. The OE3 to OE1 + OE2 ratio expressed as 14C incorporated into these three fractions was significantly higher in both patients than the corresponding ratio of 3H. Also the 3H to 14C ratio of urinary OE1 significantly exceeded that of OE3. The specific activity (S. A.) of OE3-7α-3H was by far lower than that of OE1-7α-3H, whereas the S. A. of OE3-4-14C differed much less from that of OE1-4-14C. A concept is presented describing the placental barrier to circulating androgen and the role of the placenta in the formation of OE1, OE2 and OE3.

STUDIES ON THE AROMATISATION OF NEUTRAL STEROIDS IN PREGNANT WOMEN

1964 ◽  
Vol 45 (4) ◽  
pp. 535-559 ◽  
Author(s):  
E. Bolté ◽  
S. Mancuso ◽  
G. Eriksson ◽  
N. Wiqvist ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Comparative Studies ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Radioactive Material ◽  
Placental Barrier ◽  
Therapeutic Abortion ◽  
Limited Ability ◽  
Better Than

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.

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 ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Placental Transfer ◽  
The Other ◽  
Radioactive Material ◽  
List Type ◽  
Low Degree

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.

The efficacy and safety of long-term administration of alpha-interferon and lamivudine in patients with chronic hepatitits B

2001 ◽  
Vol 120 (5) ◽  
pp. A572-A572
Author(s):  
F JABOLI ◽  
E RODA ◽  
C FABBRI ◽  
S MARCHETTO ◽  
F FERRARA ◽  
...  
Keyword(s):  
Alpha Interferon ◽  
Efficacy And Safety ◽  
Term Administration

LACK OF AROMATISATION OF CIRCULATING DEHYDROEPIANDROSTERONE AND DEHYDROEPIANDROSTERONE SULPHATE IN AMENORRHOEIC WOMEN STIMULATED WITH HUMAN GONADOTROPHINS

1965 ◽  
Vol 49 (2) ◽  
pp. 248-261 ◽  
Author(s):  
S. Mancuso ◽  
Francesca P. Mancuso ◽  
K.-G. Tillinger ◽  
E. Diczfalusy
Keyword(s):  
Pregnant Women ◽  
Ovarian Stimulation ◽  
Interstitial Cell ◽  
Follicular Phase ◽  
Radioactive Material ◽  
Dehydroepiandrosterone Sulphate ◽  
Experimental Conditions ◽  
Human Menopausal Gonadotrophin ◽  
Urine Specimens ◽  
Stimulating Hormone

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.

INDIREKTE PAPIERCHROMATOGRAPHISCHE METHODE ZUR BESTIMMUNG DER HARNOESTROGENE

1961 ◽  
Vol 38 (4) ◽  
pp. 545-562 ◽  
Author(s):  
L. Kecskés ◽  
F. Mutschler ◽  
I. Glós ◽  
E. Thán ◽  
I. Farkas ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Granulosa Cell ◽  
Iron Content ◽  
List Type ◽  
Granulosa Cell Tumour ◽  
Hydrolysis Of ◽  
Phenol Fraction ◽  
Qualitative Determination

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.

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
Keyword(s):  
Pregnant Women ◽  
Placental Perfusion ◽  
Homogeneous Form ◽  
Urine Specimens

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.

STUDIES IN THE SUPPOSED GOITROGENOUS EFFECT OF TAP WATER IN HELSINKI

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 630-636
Author(s):  
F.-E. Krusius ◽  
P. Peltola
Keyword(s):  
Tap Water ◽  
Physiological Saline ◽  
Normal Weight ◽  
The Body ◽  
Iodine Uptake ◽  
Redistilled Water ◽  
Detectable Difference ◽  
Term Administration ◽  
Long Term Experiment

ABSTRACT The study reported here was performed in order to examine the tap water of Helsinki for its alleged goitrogenous effect. In a short-term, 24-hour experiment with rats, kept on an iodine-poor diet, we noticed no inhibition of the 4-hour 131I uptake, as compared with that of animals receiving physiological saline instead of tap water. Two similar groups of rats receiving 1 and 2 mg of mercazole in redistilled water showed a distinct blockage of the 4-hour uptake, which proved the effect of this substance. In a long-term experiment of 5 weeks' duration there was no detectable difference in the body weight, thyroid weight and the 4-hour 131I uptake when the rats receiving tap water or distilled water to which 0.45 per cent of sodium chloride was added were compared with each other. Replacement of tap water by a 10 mg per cent solution of mercazole in redistilled water enlarged the thyroid to double its normal weight and increased the 131I uptake to approximately five times that of the controls. Thus our experiments failed to demonstrate any goitrogenous effect in the tap water of Helsinki. Changes similar to those produced by a long-term administration of mercazole, i. e. an enlargement of the thyroid and an increased thyroidal iodine uptake, have been shown to be due to milk collected from goitrous areas. The observations here reported confirm the importance of milk in the genesis of the goitre endemia of Helsinki. Attention is further called to the fact that a thyroidal enlargement combined with an increased thyroidal iodine uptake cannot always be taken as a sign of iodine deficiency because similar changes may be produced by the administration of goitrogens.

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