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Translation Series No. 910 TRI,NSLATION SERVICES CAN 7,.DA F4iI ICIEi OR S. T. I. NATIONAL FESEARCH COUNCIL OTTAWA FISHERIES RESEARCH BOARD OF CANADA CANArg Translation Series No. 910 The metabolism of steroid hormones By Renata Derowska and Bogdan Szukalski Original title: Metabolizm hormonciw sterY-dowych. From: Post. Biochem., Vol. 12, pp. 309-345. 1966. Translated by the Translation Bureau (MJK) Foreign Languages Division Department of the Secretary of State of Canada Fisheries Research Board of Canada Research Laboratory, Halifax, N. S. 1967 ', -DEPARTMENft OF THE SECRETARY OF STATE SECRÈTARIAT D'ÉTAT 9/0 BUREAU FOR TRANSLATIONS BUREAU DES TRADUCTIONS FOREIGN LANGUAGES DIVISION DES LANGUES DIVISION ÉTRANGÈRES TRANSLATED rnom - TRADUCTION DE IN TO --• -•À Polish English SUBJECT - SUJET Steroid Chemistry AUTHOR - AUTEUR Renata D.erowska and Bogdan Szukalski TITLE IN ENGLISH - TITRE ANGLAIS The metabblism of steroid hormones TITLE IN FOREIGN LANGUAGE - TITRE EN LANGUE dTRANGèRE Metabolizm hormonew sterydowych REFERENCE - ReFgRENCE (NAME OF BOOK OR PUBLICATION - NOM DU LIVRE OU PUBLICATION Postgpy w Biochemii ( Advances in Biochemistry ) Vol.12 PUBLISHER - eDITEUR CITY - VILLE DATE PAGES Warsaw 1966 309 - 345 60 typed pages Dr. D.R. Idler REQUEST RECEIVED FRom Fisheries Research Board OUR NUMBER 9332 REQU(S PAR NOTRE DOSSIER NO DEFARTmENT of Fisheries TRANSLATOR M ,J eicrtrhynSki MINISTÉRE TRADUCTEUR YOUR NUMBER 769 - 18 - 14 DATE COMPLETED 14 July 1967 VOTRE DOSSIER N° REMPLIE LE DATE RECEIVED May 15, 1967 REÇU LE (Advàiiices- in BiocflemiS- t;ir) 9:› "A?- if, (/7 Renata Derowsk:and Bogdan Szukalski The metabolism of steroid hormones The biosynthesis and catabolism of steroid hormones are reviewed. The physiological importance of steroid hormones, as well as their ever increasing clinical application are the reason why for a number of years investigations of their biosynthesis and catabolism have been conducted. The basic methods used for that purpose are perfusion of a gland or some other organ with metabolites and an analysis of the resulting products, incub- ation of metabolites with pieces or homogenates of gland tissue (adrenal glands, testes, ovaries, placenta) and the analysis of blood leaving the gland, blood of the peripheral circulatory system, and urine. The application of tracer compounds accel- erated considerably the progress in this field and supplied much new information, permitting to create a fairly complete 'picture of the metabolism of steroid hormones. › M.Sc.Eng., Senior Instructor, Institute of General Chemistry, Medical Academy, Warsaw M.D.,M.Sc. (Chem) Assistant Professor, Institute of General Chemistry, Medical Academy in Warsaw, and the II Internal Medicine Division, the Bielariski Hospital in Warsaw. List of abbreviations applied: DHA - dehydroepiandrosterone; androsteAtione 4-androstene-3,17-dione; ACTH - adrenocorticotropic hormone , Translator's note: A Polish-English biochemioal dictionary not being available, the following 1 dictionaried and reference books were used to clarify terminological problems 1. Diotionary of Organic Compounds. Eyree & Spottiewoods. London, 1965 • ' 2. Merok Index, 1965. 3. Physiology and Bioohemistry. Bell,Davidson, Scarborough, 1965. 4. Review of Physiological Chemistry. Harold A. Harper, 1965 5. Biochemistry. West Todd Mason, Van Bruggen, 1966. •••2 • 2 • The division of steroid hormones is based on their physio- logical activity conditioned by their chemical structure. All the steroid hormones can be derived from three synthetic hydrocarbons: pregnane built of 21 carbon atoms, androstane of 19 atoms and estrane of 18 atoms. In a live system, cholesterol is the intermediary compound in the process of formation of all steroid hormones. Its com- plete biosynthesis was the subject of exhaustive works by Supniewski (158) and lately by Clayton (29). We shall deal with changes of cholesterol leading to steroid hormones: gestagens, cortice-steroids androgens and estrogens and with the catabolism of those hormones. I. Routes of biosynthesis of steroid hormones 1 . "2..q.AIP 521 * The first stage of biosynthesis of pregnancy hormones taking place in the corpus luteum, adrenal glands, testes, ovaries and the placenta, is based on a degradation of the side chain of cholesterol. Solomon et al. (156) established that homogenates of the adrenal gland of a cow produce 2O_fl (II) from cholesterol (I). The subsequent stage of cholesterol trans- formation after 201 hydroxylation is hydroylation in position 22 with formation of 20/1 , 22 a -dihydroxycholesterol (III) (145) which is transformed into pregnenolone(IV) by the action of 20, 22-desmolase, with detachment of the side chai n in thea form of l'ç Ti-anslatoris note: Term not found in English books. Appnrently a collective name for pregnancy hormones. *• * 3 . 3 isocaproilx aldehyde (143, 144, 163). Of other oxidized cholesterol derivatives, 22-hydroxycholesterol is a better substrate for de- composing enzymes than cholesterol itself, and 22-ketocholesterol does not decompose in those conditions. 20P 41.ydroxy-20-ketochol- esterol is not sensitive to the action of desmolase (30), and therefore cannot be considered as an intermediate product of the transformation of cholesterol into "gestagene. In pregnenolone in position 3, under the influence of dehydrogenase found in the microsomes of the adrenal glands, a reversible transformation occurs of the hydroxyl group Into the ketone group with formation of Z1 5_ pregnene-3,20-diofflV); subsequently under the influence of A5-3-ketoisomerase a shift of the double bond into a conjugatalposition in relation to the newly formed ketone group takes place. The product of those transformations is the pregnancy hormone progesterone (VI), (scheme 1). The cyclical corpus luteum produces in 24 hours about 20 mg of progesterone, whereas in the cortex of the adrenal glands about 250 mg of it is formed during that period (14, 78). Under the influence of dehydrogenases 20- othydroAy-AA-pregnenone-3 and its isomer 20 f3- / can result from progesterone and from pregnenolone 200C-hydroxy--pregnenol- 3 is formed. Talalay et co-workers ( 161, 176) obtained from Pseudomonas testosteroni the isomerase of 21;5-3-ketesteroids i participating •••4 See:nOte ion page 2. in formation of progesterone, in crystalline form. It shows its _optimum activity between - Schemat 1. Biosynteza gestagenôw Scheme 1. Biosynthesis ofn gestagens" 6 pH and 8 pH, is competitively inhibited by a low concentration 31 of 1718 -estradiol, 19-nortestosterone and 17-dihydroequilenin (67). Among animal tissues, it is in the adrenal glands, where this enzyme is present most abundantly (43, 44). The reversibil- ity of the isomeration reaction is pointed out by investigations conducted by Ward and Engel (177), Who reported that extracts of acetone powder from the adrenal glands of sheep cause a transformation of androster;hone into 3/3 -hydroy„y-45-androsten- 17-one. 2. Corticosteroids Among more than 70 steroids isolated from the cortex of adrenal glands (182) only 7 show to a greater or lesser degree the ability of r.emoving the disturbances occurring after removal See footnote on page Z. " See footnote on page 1. •••5 .5 • of the cortex. They are cortisol(XV), cortisone(XVI), corticosterone(XI) îl-dehydrocorticosterone(XII), cortexolone(IX) and aldosterone(X)II). Their systematic names and synonyms used are compiled in Table 1. Table 1 Sysjpematic names and used synonyms of fundamental corticosteroids \C cram° n name . Synon,yms in use Syst emati name Cortisol hydr000rti sol ; 17 -hydro3eoorticouterone ; A, 4 -pregnene -lip , 174 '21 -triol -3,20-di one Kendall '8 substance 'TH; Rei abstain's substance "M" Cortisone 7-hydroxy -11 -dehydr000rtiooster one ; Kendall 's substance "E"; Reichstein's substance 'IF'? A4 -pregnene -17J,21 -di ol 1 ,21 -tri one Corti oost erone Kendall 'a substance Hs" R ohstein '9 substance "HI' A4 -pregnene-np,21 -diol -3, 20 -dione 11 -dehydrocorti 4 cc st e ro ne Kendall's substance HA" -pre gnarl , —21 -al -3,11 ,20-tri one Cortexone 11 -desorycorti cost erone ; 'DOC ; 21 -hydroxyp ro gesterone ; et Reichr+ein's bstance "CI" LN2-preg,non -21-o 1 -3 ,20 -di one Cortex°lone 17d-hydr oxy cot BX o ne ; 17-hydrox,y -11 -desoxyoortio ester one ; ll -des ox,y oorti s ol ; Reichstein's substance "Sit 4 -pregne.ne -17,4 21 -di ol -3, 20-dl one Aldosterone A.4 -pre gnene -Ile, 21 --dial -3,20-di —18a1 Apart from cortex hormones proper with molecules built of 18 carbOn atoms, etxx compounds with 18 carbon atoms in the mole- also cule have/been isolated from the adrenal glands, pertaining to female sexual hormones as well as compounds of androgenic pro- perties containing 19 carbon atoms (180, 181). ...6 . 6 . 312 312 R. DABROWSKA, B. SZUKALSKI [41 0 m 4 0 • 0 0 X tn 0 e e o 9.1 0 O 0 OI1 O fl x 0 o u II el 0 ,p o p O X 0 se • CH > O 0 /IF re) (:)C=, ) t._ & 2. ,C c z -2 0 0 0 , o Translator' s note 11 r. Roman :•rimerals to denote The authors use e steroid hormones both 1.-n the text (in m and tt.0 brackets af ter the nar,é;) in diagrams. ctj However, this sys tem i*pears to be some- »ri what confusing, since 1.n several cases the sanie Roman numeral is used to denote compounds differing buth in naine and stereochemical structure. These numerals are: )(II in diagrams 2 and LMV to LX:k= in dinrrams 11 and 12. LMV, IMI/1 and LXVI1T are shown in diagram 12, but not mentioned in the text 0 I ntbt find any c..„-Çplanation in text books. could On the other hand what, is confusing to me may be clear to a specialist in steroid chemistry. Nevertheless I thought it worthwhile to raise • this point. ••• • 7 • The main route of biosynthesis of glucocorticosteroids is based 313 on hydroxylations of progesterone (VI) in the order 17c.(, 21, 11 p .
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