ACETATE AND CHOLESTEROL METABOLISM IN THE HUMAN FOETO-PLACENTAL UNIT AT MIDGESTATION.

1970 ◽  
Vol 63 (1) ◽  
pp. 91-104 ◽  
Author(s):  
G. Telegdy ◽  
J. W. Weeks ◽  
U. Lerner ◽  
G. Stakemann ◽  
E. Diczfalusy

ABSTRACT As the first part of a series of investigations on acetate and cholesterol metabolism, the conversion of acetate to cholesterol was studied in the various compartments of the midgestation foeto-placental unit in perfusion experiments carried out for 90 min at 35–36°C. Following their removal at laparotomy two complete foeto-placental units were perfused each with 5.0 mCi of uniformly labelled sodium acetate-14C + 5.0 mCi of cholesterol-7α-3H. The study was completed by the separate perfusion of two isolated midgestation foetuses and two midgestation placentas. The doses administered in each of these four last experiments were 2.5 mCi of 14C-labelled acetate and 2.5 mCi of 3H-labelled cholesterol. Cholesterol was isolated in a radiochemically homogeneous form from each of the tissues studied. The cholesterol isolated from the placentas, placental perfusates and from the blood bathing the placenta from the maternal side (»maternal perfusates«) contained exclusively 3H-label. On the other hand, the cholesterol isolated from all foetal livers, adrenals, testicles, 3 of 4 residual foetal tissues and 1 out of 4 foetal perfusates also contained significant quantities of 14C-label. It is concluded, that the midgestation human placenta is not capable of synthesizing cholesterol from acetate, but that the conversion of acetate to cholesterol is a quantitatively significant metabolic pathway in the human foetus at midgestation.

1970 ◽  
Vol 63 (1) ◽  
pp. 119-133 ◽  
Author(s):  
G. Telegdy ◽  
J. W. Weeks ◽  
D. F. Archer ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Two complete foeto-placental units were perfused at midgestation with 5.0 mCi of uniformly labelled 14C-sodium acetate plus 5.0 mCi of cholesterol-7α-3H and two isolated foetuses were perfused with 2.5 mCi of 14C-labelled sodium acetate plus 2.5 mCi of cholesterol-7α-3H. The perfusions were carried out at 35–36°C for 90 min. The foetal adrenals, livers, testes and perfusates were analyzed and various labelled steroids were isolated in a radiochemically homogeneous form. Major quantities of 14C- and 3H-labelled pregnenolone (3β-hydroxy-pregn-5-en-20-one) and dehydroepiandrosterone (3β-hydroxy-androst-5-en-17-one) were isolated from the foetal perfusates, livers and adrenals. Minor amounts of 14C- and 3H-labelled progesterone (pregn-4-ene-3,20-dione) were isolated from the perfusates and adrenals, and 17α-hydroxy-progesterone (17α-hydroxy-pregn-4-ene-3,20-dione) and androstenedione (androst-4-ene-3,17-dione) from the perfusates. Smaller amounts of exclusively 14C-labelled androstenedione were isolated also from the adrenals. No labelled progesterone, androstenedione or testosterone (17β-hydroxy-androst-4-en-3-one) was detected in the testes. Attempts to isolate 20α-dihydroprogesterone (20α-hydroxy-pregn-4-en-3-one) or 20β-dihydroprogesterone (20β-hydroxy-pregn-4-en-3-one) from the perfusates, adrenals and livers failed. No labelled cortisol (11β,17,21-trihydroxy-pregn-4-ene-3,20-dione) or corticosterone (11β,21-dihydroxy-pregn-4-ene-3,20-dione) was detected in the adrenals, and no testosterone, oestrone (3-hydroxy-oestra-1,3,5(10)-trien-17-one) or 16α-hydroxy-dehydroepiandrosterone (3β,16α-dihydroxy-androst-5-en-17-one) in the perfusates. Pregnenolone and dehydroepiandrosterone (which were present in approximately equal amounts) accounted for as much as 95% of all steroids isolated from all sources. The bulk of these two steroids was isolated from the perfusates. The 14C/3H ratio of the pregnenolone and dehydroepiandrosterone isolated from the conjugated fraction of the perfusates was much higher than that of the unconjugated compounds. It is concluded that the midgestation human foetus is capable per se of carrying out the de novo synthesis of major quantities of pregnenolone and dehydroepiandrosterone. It is suggested that in foetal steroidogenesis acetate is utilized predominantly via a conjugated pathway and circulating cholesterol mainly via an unconjugated pathway.


1970 ◽  
Vol 63 (1) ◽  
pp. 39-49 ◽  
Author(s):  
G. Benagiano ◽  
S. Mancuso ◽  
B. de la Torre ◽  
E. Diczfalusy

ABSTRACT One female and one male foetus were perfused at midpregnancy with 17β-oestradiol-16-14C,17α-3H and metabolites were isolated in a radiochemically homogeneous form from the perfusates and various foetal tissues. The 3H/14C ratio of the perfused material was 60.2. Unconjugated and conjugated 17β-oestradiol and oestrone were isolated from all tissues studied. The 3H/14C ratio of the oestradiol isolated from all tissues, except the liver, agreed with the perfused one. The oestrone isolated from different sources did not contain any 3H-label. Unconjugated oestriol and conjugated oestriol, 16-epi-oestriol, 16α-hydroxy-oestrone, 16-oxo-oestradiol and 15α-hydroxy-oestradiol were isolated from the extracts of the livers. No 3H-label was present in 16α-hydroxy-oestrone, and only traces, if any, in 16-oxo-oestradiol. On the other hand, the isotopic ratios of 16-epi-oestriol, oestriol and 15α-hydroxy-oestradiol were between 1.5 and 5.0. It is concluded that a small but significant part of the oestriol, 16-epi-oestriol and 15α-hydroxy-oestradiol synthesized by the foetal liver is formed via a direct hydroxylation of oestradiol.


1970 ◽  
Vol 63 (1) ◽  
pp. 105-118 ◽  
Author(s):  
G. Telegdy ◽  
J. W. Weeks ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT Two midgestation placentas were perfused with 2.5 mCi of uniformly labelled 14C-sodium acetate plus 2.5 mCi cholesterol-7α-3H. and two complete foeto-placental units were perfused with 5.0 mCi of 14C-labelled sodium acetate plus 5.0 mCi of cholesterol-7α-3H. The perfusions were carried out at 35–36°C for 90 min. After the perfusion of the isolated placentas, the following 3H-labelled steroids were isolated from the placentas as well as from the perfusates in a radiochemically homogeneous form: pregnenolone (3β-hydroxy-pregn-5-en-20-one), progesterone (pregn-4-ene-3,20-dione), 20α-dihydroprogesterone (20α-hydroxy-pregn-4-en-3-one), 20β-dihydroprogesterone (20β-hydroxy-pregn-4-en-3-one), 17α-hydroxy-pregnenolone (3β,17α-dihydroxy-pregn-5-en-20-one),dehydroepiandrosterone(3β-hydroxy-androst-5-en-17-one) and 17β-oestradiol (oestra-1,3,5(10)-triene-3,17β-diol). The same compounds were also isolated from the placentas following the perfusion of the complete foeto-placental units. With the exception of pregnenolone and progesterone, all steroids were isolated in minute quantities. None of the steroids isolated contained any 14C-label. It is concluded that the midgestation human placenta is not capable of carrying out any de novo steroid synthesis from acetate and that cholesterol is an obligatory precursor in placental steroidogenesis.


1971 ◽  
Vol 66 (4) ◽  
pp. 711-719 ◽  
Author(s):  
H. A. van Leusden ◽  
M. Siemerink ◽  
G. Telegdy ◽  
E. Diczfalusy

ABSTRACT In order to investigate the synthesis of squalene and lanosterol in the human foeto-placental unit at midgestation, two complete foeto-placental units, two isolated midgestation foetuses and two isolated midgestation placentas were perfused with [14C] sodium acetate immediately following their removal at laparotomy. The perfusions were carried out at 36°C for 90 minutes, administering 5.0 mCi (foeto-placental units), or 2.5 mCi (separate perfusions of foetuses or placentas) amounts of [14C] sodium acetate. Chromatographic evidence indicated the presence of [14C] squalene-like material in the extracts of all adrenals and livers. Radiochemically homogeneous squalene was isolated in the form of squalene dodecabromide from one adrenal and two liver extracts, which were studied more in detail. In the extracts of all placentas, testicles, carcasses and perfusates, the presence of any [14C] squalene was excluded by crystallization. Sufficient material for the identification of [14C] lanosterol was present in the extracts of three adrenals, three livers, four testicles and two carcasses. From all these extracts radiochemically homogeneous [14C]-lanosterol was isolated. The [14C] lanosterol-like material present in all perfusates was so limited that it precluded further identification. In the extracts of three placentas, the presence of any [14C] lanosterol was excluded by crystallization. From the extract of a separately perfused placenta a minute amount of radiochemically homogeneous [14C] lanosterol was isolated. It is concluded that the midgestation human foetus is capable of synthesizing major quantities of squalene and lanosterol. Little, if any, squalene and lanosterol are formed by the midgestation human placenta.


1985 ◽  
Vol 63 (3) ◽  
pp. 183-186 ◽  
Author(s):  
W. Gibb ◽  
J. C. Lavoie ◽  
M. Morin-Gonthier

Recent studies from our laboratory and others have shown that Km values for steroid substrates of the 3β-hydroxysteroid dehydrogenase in the human placenta were in the nanomolar range compared with micromolar values previously described. The purpose of the present study was to measure the kinetic parameters of the 3β -hydroxysteroid dehydrogenase in other human tissues, namely the ovary and chorion laeve, and to determine whether they were similar to those of the placental enzyme. In chorion laeve microsomes the 3β-hydroxysteroid dehydrogenase had Km values for dehydroepiandrosterone and pregnenolone similar to those found in placenta. Microsomes from human ovaries, on the other hand, had Km values for both substrates 10- to 20-fold higher. However, the ability of various steroids to inhibit the ovarian enzyme was similar to that previously described from the placenta and the chorion laeve.


1972 ◽  
Vol 27 (5) ◽  
pp. 528-530 ◽  
Author(s):  
Helga Wittmann ◽  
Helmut Rathmayr

Benzylmalonyl Chloride reacts in the presence of sodium acetate in boiling benzene to give tribenzyl-phloroglucinol-triacetate, however with sodium chloroacetate to 3,5-dibenzyl-6-phenethylpyran-2,4-dion. In both cases trimerisation of benzylketene or benzylketene carboxylic acid chloride occurs. On the other hand, benzylmalonylchloride reacts with sodium benzoate and sodium phenylacetate via a dimeric benzylketene carboxylic acid chloride under the loss of phosgene to yield cyclopentadienyl derivatives.


1970 ◽  
Vol 65 (4) ◽  
pp. 663-674 ◽  
Author(s):  
R. S. Mathur ◽  
D. F. Archer ◽  
N. Wiqvist ◽  
E. Diczfalusy

ABSTRACT In order to assess the quantitative significance of the de novo cholesterol synthesis in the foeto-placental unit at midgestation, two midgestation foetuses and two complete foeto-placental units were perfused with [14C]-sodium acetate immediately following their removal at laparotomy. The perfusions were carried out at 36°C for 120 min administering 3.0 and 6.0 mCi of [14C] sodium acetate, respectively. The amount of [14C]-cholesterol formed was estimated on the basis of the recovery of [7α-3H]-cholesterol internal standard present in the radiochemically homogeneous cholesterol isolated from the various tissues. The cholesterol isolated from the placentas was devoid of any [14C] label. On the other hand, [14C] cholesterol was isolated from all perfusates, as well as from all foetal tissues studied, including the adrenals, livers, testicles, brains and residual foetal tissues. The average quantity of radiochemically homogeneous [14C] cholesterol formed by the four foetuses corresponded to 0.68% of the radioactive material perfused: 0.45% was isolated from the liver, 0.13% from the adrenals, 0.01% from the testicles and 0.08% from the perfusates. Cholesterol sulphate was also isolated from the extracts of adrenals, livers and perfusates. The quantity of [14C] cholesterol sulphate formed was much less than that of [14C] cholesterol; following correction for procedural losses, the total amount of [14C] cholesterol sulphate isolated did not exceed 0.01% of the perfused material. It is concluded that the midgestation human foetus synthesizes large quantities of cholesterol, utilizing small molecular material such as sodium acetate as a precursor and that part of the cholesterol synthesized by the foetus is secreted to the placenta.


1963 ◽  
Vol 41 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Harold J. Perkins ◽  
D. W. A. Roberts

Sodium acetate-1-C14 or (in one case) succinic-2,3-C14 acid was fed to both immature and mature leaves of four monocotyledons (lily, oats, philodendron, and tradescantia), three dicotyledons (red clover, petunia, geranium), a gymnosperm (spruce), and a pteridophyte (Boston fern). These experiments have indicated that chlorophyll synthesis and thus chlorophyll turnover in the mature leaves of the monocotyledons is very slow or non-existent. On the other hand, considerable amounts of C14 were incorporated into the dihydroporphyrins isolated from the mature leaves of the dicotyledons, the gymnosperm, and the pteridophyte.


1966 ◽  
Vol 51 (4) ◽  
pp. 599-608
Author(s):  
Dale M. Peterson ◽  
James C. Warren

ABSTRACT Glutamate dehydrogenase (EC 1. 4. 1. 3.) has been purified approximately 3700 fold from human placenta. The effects of sex hormones and co-factors on the activity and stability of this preparation have been studied. NAD+ was noted to activate this enzyme at high concentrations while NADP+ did not. Mg2+ was shown to be a competitive activator of glutamate with NADP+ as cofactor and an uncompetitive inhibitor of glutamate with NAD+ as cofactor. With NAD+ as cofactor, steroids at concentrations physiological for placenta had no effect on activity while significant inhibition of initial velocity by 1.0 μm oestrone and 17β-oestradiol and 2.0 μm progesterone was seen with NADP+ as co-factor. The stability of the enzyme was uneffected by several steroids alone at 20 μm concentrations. The stability of the enzyme was markedly decreased by NADPH but natural steroids at physiological concentrations failed to potentiate this cofactor induced instability. Mg2+ ion, ATP and ADP at physiological concentrations, on the other hand, clearly protect the enzyme against NADPH. These observations militate against steroid effects on stability but do not exclude steroid inhibition of activity with NADP+ as cofactor as a possible mechanism of steroid action, at least in placenta.


2020 ◽  
Vol 11 (4) ◽  
pp. 468-469
Author(s):  
S. Yu. Khazan
Keyword(s):  

Pointing to the scarcity of our information about the very first stages of the development of the placenta, the scarcity depends, on the one hand, on the fact that the studied material, the products of miscarriages, in most cases has a pathological character, on the other hand, on the other a proper assessment of his age is not always possible - and prefaced by a description of seven apparently normal drugs, the author expresses the following view of the development of the placenta.


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