[Testosterone metabolism in discrete areas of the brain in rat fetuses]. / Metabolizm testosterona v diskretnykh oblastiakh mozga plodov krys.

Experiments in vitro with further thin-layer chromatography of steroids were staged to investigate changing of 3H-testosterone into 3H-estradiol-17 beta and 3H-5 alpha-reduced metabolites in a fraction of 1000 g of homogenates of the medial preoptic area (MPA), the paraventricular nuclei (PVN), the dorsal vagal complex (DVC) of the lower cerebral trunk, the rostral and caudal parts of the amygdaloid complex (ACr and ACc) of the brain of 21-day male and female rat fetuses. The activity of aromatase (AA) and 5 alpha-reductase (AR) was detected in all investigated areas. AA was maximum in PVN of females and minimum in ACc of males and females. The production of 5 alpha-dehydrotestosterone prevailed among 5 alpha-reduced products in PVN, DVC and ACr, 5 alpha- and rostane-3 alpha and 17 beta-diol--in MPA and ACr, AR in ACr was much higher than in ACc. AR in DVC of females was slightly higher than in males. Sex differences in the other cerebral areas were undetectable. The results of the investigation suggest that the above cerebral structures are dependent on sex hormones.

[Simple synthesis of a complete set of unconjugated norethisterone metabolites and their deutero-analogs]. / Prostoi sintez polnogo nabora nekon"iugirovannykh metabolitov norétisteronea i ikh deiteroanalogov.

The short-step synthesis of all norethisterone (NET) hydrogenated metabolites and their deuteroanalogues has been accomplished. Reduction of NET by NaBH4 in the presence of N,N,N',N'-tetramethylethylenediamine provided 19-norpregn-20-yn-3,17-diols as a mixture of 3- and 5-epimers. The individual isomers were isolated by flash chromatography and oxidyzed by PyHCrO3Cl into 5 alpha- and 5 beta-dihydro-NET. These products were converted, on isotopic exchange with D2O--MeOD in alcaline conditions followed by reduction with NaBD4, into four stereoisomeric 2,2,3,4,4-pentadeuterated 19-norpregn-20-yn-3,17-diols; two isomeric 2,2,3,4,4,16,16,17-octadeuterated estrane-3,17-diols were also isolated as side products. All compounds obtained will be used as internal standards for chromato-mass-fragmentographic analysis.

[Molecular and crystallographic structure of D-11-aza-19-nortestosterone]. / Molekuliarnaia i kristallicheskaia struktura D-11-aza-19-nortestosterona.

Crystal and molecular structure of D-11-aza-19-nortestosterone monohydrate C17H25NO2.H2O (a 8,288(2), b 12,433(2), c 7,570(2) A, beta 90,25(1) degrees; space group P2(1), R 8.3%) has been determined by X-ray analysis. Its comparison with the molecular structure of D-19-nortestosterone showed that the decrease in the hormonal activity upon 11-aza-substitution may be due to difference in chemical properties of imino and methylene groups.

[Synthesis of pentadeutereted pregnanediol glucuronide]. / Sintez pentadeiterirovannogo gliukuronida pregnandiola.

The synthesis of 2,2,3,4,4-pentadeuteropregnanediol glucuronide sodium salt, an isotopically substituted analogue of the main progesterone metabolite, have been accomplished. The starting 5 beta-pregnane-3 alpha, 20 alpha-diol bis-tert-butyldimethylsilyl ether was converted by consecutive selective desilylation and oxidation into 5 beta-pregnane-20 alpha-ol-3-one 20-monoether. The latter's alpha-hydrogen atoms were exchanged for deuteriums by treatment with D2O-MeOD mixture catalysed with sodium carbonate, and 2,2,4,4-tetradeuterated 3-ketone formed was reduced by sodium borodeuteride into 2,2,3,4,4-pentadeuterated pregnanediol 20-silyl ether. The ether was glucuronidated under Koenigs-Knorr method with (2,3,4-tri-O-acetyl-alpha-D-glucopyranosylbromide) uronate in the presence of Ag2O. The completely protected pentadeuterated pregnanediol glucuronide resulted was converted into the above mentioned sodium salt by consecutive hydrofluoric acid hydrolysis and treatment with aqueous sodium bicarbonate solution.

[Synthesis of the leukotriene A4 methyl ester via acetylene intermediates]. / Sintez metilovogo éfira leikotriena A4 na osnove atsetilenovykh soedinenii.

The strategy of acyclic eicosanoid synthesis via polyacetylenic intermediates is examplified by the synthesis of the racemic leukotriene A4 methyl ester. Leukotriene synthons, namely, trideca-1,4,7-triyne and methyl 6-formyl-5,6-trans-epoxyhexanoate, were synthesised using propargylic alcohol (thrice) and 1-heptyne as starting materials. In the course of the synthesis all new carbon-carbon bonds were created through acetylenide anion condensations and (Z)-double bonds are introduced by triple bond hydrogenations. The strategy provides a straightforward and stereospecific synthetic pathway.

[Synthesis of leukotriene A4 methyl ester via acetylene intermediates]. / Sintez metilovogo éfira leikotriena A4 na osnove atsetilenovykh soedinenii.

Rac-leukotriene A4 methyl ester has been synthesized from propargylic alcohol and 1-heptyne. The synthetic strategy involves the assembly of carbon chain by acetylenide anion condensations and the introduction of (Z)-double bonds by the triple bond hydrogenation.

[Conformation of the dienone system of delta 4,9-19-nor-3-ketosteroids from x-ray analysis data and its relation to reception and hormonal activity]. / Konformatsiia dienonovoi sistemy delta 4,9-19-nor-3-ketosteroidov po dannym rentgenostrukturnogo analiza i ee sviaz' s retseptsiei i gormonal'noi aktivnost'iu.

Basing on the data of the X-ray analysis of 2 beta-methylestr-4,9-dien-3-one-17 beta-ol (C19H26O2) and A-ring unsubstituted steroid 4,9-dien-3-ones, the noncomplanarity and flexibility of the conjugated dienone system in these transformed steroids has been demonstrated. The results have been also confirmed by UV spectroscopy. The ability of the dienone system to assume conformations with the out of- plane C3 = O3 and/or C9 = C10 bonds allows the AB-fragment of the steroid molecule to adopt the conformations required for interacting with various receptors. This property may also account for a simultaneous enhancement of several hormonal activities upon such a modification of steroids. The results of the X-ray analysis of 2 beta-methylestra-4,9-dien-3-one-17 beta-ol (space group P2(1)2(1)2(1), a 8,543(2), b 9,783(2), c 18,690(7) A, R 8,7%) are presented.

[Comparative determination of progesterone in the blood plasma by radioimmunological and chromato-mass-fragmentographic methods]. / Sravnitel'noe opredelenie progesterona v plazme krovi radioimmunologicheskim i khromato-mass-fragmentograficheskim metodami.

A comparative determination of progesterone in the blood plasma was performed using a radioimmunoassay (RIA) and 2 variants of a chromato-mass-fragmentographic (CMF) method. A deuterated internal standard, capillary gas-liquid chromatography and 3-enol-3-tret-BDMS and 3.20-bis-enol-bis-BDMS progesterone ethers as chromatographied derivatives were employed. Both derivatives made it possible to perform CMF determination using simplified variants of the method. The variants of the CMF method were employed as references for RIA of progesterone. Comparison of the results of the CMF and RIA methods indicated RIA significance (r = +0.99) in using antiserum to the conjugate 3-(O-carboxy methyl)-oxime of progesterone with bovine serum albumin injected to rabbits.

[Comparative determination of norethisterone in the blood plasma by radioimmunological and chromato-mass fragmentographic methods]. / Sravnitel'noe opredelenie norétisterona v plazme krovi radioimmunologicheskim i khromato-mass-fragmentograficheskim metodami.

Radioimmunoassay (RIA) and two variants of the chromato-mass fragmentographic (CMF) method were used for comparative determination of norethisterone (NET) in the blood plasma. A deuterated internal standard, capillary gas-liquid chromatography and chromatographed derivates: 3-enol-3-tret-butyldimethylsilyl-17-tri-methysilyl and 3-enol-3,17-bis-tret-butyldimethylsilyl NET esters were used. Both derivates provide for CMF determination after simplified variants. They were used as references for RIA determination of NET. Comparison of the CMF and RIA results indicate to the significance of RIA determination (r = 0.979) while employing antiserum to NET conjugate 3-(0-carboxymethyl)-oxime with bovine serum albumin injected to rabbits.

PIP: Norethisterone (NES), a synthetic gestagen, is widely used in gynecological practice for contraception and therapy. Its quantitative determination in blood plasma is important for clinical and pharmacological studies. Radioimmunological assays (RIAs), routinely used for these analyses, are simple and easy to perform. However, they are not selective and depend strongly on the specificity of the antiserum used for the RIA. Therefore, RIAs should be controlled using a reliable reference method. In order to develop an independent reference method, RIA data are compared with the results of chromato-mass-fragmentographic (CMF) analysis. A study was performed on samples of blood plasma taken from women who used NES as a therapeutic agent. RIAs were performed with highly specific antibodies produced in rabbits in response to injections of the conjugate of NES 3-(0-carboxy-methyl)-oxime with bovine albumin serum. A good correlation was obtained between the RIA and CMF data; the regression coefficients were nearly the same. It is concluded that: 1) CMF analysis can be used as a reference method for monitoring RIA data relative to NES levels in blood plasma, 2) RIA is a reliable (r=.979) method for the quantitative determination of NES, and 3) the proposed antiserum is a specific agent for the radioimmunological determination of NES in blood plasma.

[Synthesis and anti-aggregating activity of 11-deoxyprostacyclin]. / Sintez i antiagregatsionnaia aktivnost' 11=dezoksiprostatsiklina.

11-Deoxyprostacyclin was prepared in three stages starting from the 11-deoxyprostaglandin F2 alpha methyl ester. 11-Deoxyanalog showed 0,9% of natural prostacyclin potency in inhibition of platelet aggregation.

[Effect of various 1,3,5(10)-estratrien derivatives on the estrogen receptor transport into the nucleus in the guinea pig uterus]. / Vliianie razlichnykh proizvodnykh 1,3,5(10)-éstratriena na transport retseptora éstrogenov v iadro v matke morskoi svinki.

The capacity of five derivates of 1, 3, 5 (10)-estratrien to be transported together with estradiol receptor from the cytoplasm into the nucleus in the uterus of sexually immature guinea pig was investigated. The extent of this transport was assessed by the amount of estrogen receptor in the nucleus following incubation of the uterine slices in the presence of the compound tested (2.5.10(-7) M). The content of estrogen receptor in the nucleus of the intact guinea pig uterus served as control. Incubation of the uterine slices with compounds containing 17 beta-hydroxyl group (2-brom-1, 3, 5 (10)-estratriendiol-3, 17 beta, 4-brom-1,3,5 (10)-estratriendiol, 3, 17 beta, 1, 3, 5 (10)-estratrienol-17 beta), led to a 1.9--4.2-fold increase in the content of nuclear estrogen receptor, this pointing to the transport of the estrogen receptor complex with these compounds into the nucleus. Two compounds (1, 3, 5 (10) estratrienol-3 beta and 3-methoxy-1, 3, 5 (10)-estratrien) contained no 17 beta-hydroxyl group and failed to increase the contents of the estrogen receptor in the nucleus in comparison with control. 17 beta-hydroxyl group is apparently necessary for the formation of conformative changes in the receptor molecule transforming the steroid-receptor complex into the active one, capable of transporting into the nucleus.

[11-azasteroids. V. Hormonal properties of 11-azaestranes]. / 11-azasteroids. V. Hormonal properties of 11-azaéstranes.

Experiments were conducted on sexually-immature female rats, ovariectomized mice and castrated male rats. Hormonal properties of some 11-azaestran were studied. As shown, introduction of azafunction into the position of the 11 molecule of the steroid sharply reduced the hormonal activity, irrespective of other functions in the molecule determining the reference of the steroid to the estron, estradiol, or 19-nortestosterone series.

[Characteristics of the estrogen receptor system of the guinea pig uterus]. / Kharakteristika éstrogenretseptornoi sistemy matok morskikh svinok.

Physico-chemical parameters of estradiol-receptor interaction in guinea pig uterine cytosol (velocity constants of association and dissociation, half-life time of estradiol-receptor complex, and the value of free energy change) were studied. The number of receptor sites per cell was calculated. It was shown that under conditions of different degree of approximation to the equilibrium, the affinity percentage in the system under study remained unchanged for the majority of steroids, this pointing to the achievement of equilibrium in these cases. The steroid affinity to the analyzed R-system depended on presence of intact 3- and 17beta-hydroxils with somewhat greater significance of 3-(phenolic) hydroxil of steroid molecule.

[Study of the specificity of the estradiol-binding system in the uteri of guinea pigs]. / Izuchenie spetsifichnosti éstradiolsviazyvaiushchei sistemy matok morskikh svinol

The authors analyzed the affinity of the steroids belonging to the estran series to the estradiol-binding system of the guinea pig uteri. The presence of free hydroxyl groups in positions 3 (phenol) and 17beta and their interorientation proved to determine the interaction with the recptor system of the guinea pig uterus. The data obtained indicated that the biological activity of the steroids was determined by the peculiarities of their structural interaction with the receptor systems of the uteri.