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Effect of Progestins on Nucleic Acids and Others in the Ovariectomiz

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Effect of Progestins on Nucleic Acids and Others in the Ovariectomiz Title Pharmacological researches on progestin action [II] : effect of progestins on nucleic acids and others in the ovariectomized rat uterus Sub Title Author 加藤, 礼子(Kato, Reiko) 中村, 幸子( Nakamura, Yukiko) 木村, 都( Kimura, Miyako) 中村, 悦郎( Nakamura, Etsuro) Publisher 共立薬科大学 Publication year 1970 Jtitle 共立薬科大学研究年報 (The annual report of the Kyoritsu College of Pharmacy). No.15 (1970. ) ,p.61- 68 Abstract Notes 原報 Genre Technical Report URL https://koara.lib.keio.ac.jp/xoonips/modules/xoonips/detail.php?koara_id=AN00062898-0000001 5-0061 慶應義塾大学学術情報リポジトリ(KOARA)に掲載されているコンテンツの著作権は、それぞれの著作者、学会または出版社/発行者に帰属し、その権利は著作権法によって 保護されています。引用にあたっては、著作権法を遵守してご利用ください。 The copyrights of content available on the KeiO Associated Repository of Academic resources (KOARA) belong to the respective authors, academic societies, or publishers/issuers, and these rights are protected by the Japanese Copyright Act. When quoting the content, please follow the Japanese copyright act. Powered by TCPDF (www.tcpdf.org) No. 16 (1970) Pharmacological Reseaches on Progestin Action ;II] : E 妊ect of Progestins Progestins on N ncleic Acids and Others in the Ovariectomized Rat Uterus Reiko KATO, Yukiko NAKAMURA, Miyako KIMURA and Etsuro NAKAMURA •l之 ’ fhc effects of pro 芯csteronc and synthetic progestins, i.e., rctroprogesterone, megestrol acetate, acetate, ethynocliol diacetate, and 19-norethysterone, on uterine RNA, DNA, protein contents contents and others were studied in ovariectomizcd adult rats. 1》rogcsterone ancl retroprogesterone decreased the estrogen-induced e丘ects on the uteru 百. ::Vlc 只estrol acetate and cthynodiol diacetatc were proved to have the cstrogenic activities activities themselves and also to enhance the increasing of the uterine phosphates-levels estradiol. by estradiol. H) ふforethysterone was estrogenic, as well as anclrogenic-anabolic, therefore, the the effects of this steroid on RNA/DNA ratio, protein concentration and uterine weights were were varied from the subjects. No particular change was ol 川 n・ed in DNA concentration by any treatment studied in adult rats. The relationships ht イ； ween changes of uterine phosphates phosphates and biological activiti ℃s were discussed. In recent years, estradiol has been reported to have a stimulatory effect on the synthesis of of nucleic acids or protein in the uterus.1,2,3,4) HoweYer, on those of progesterone or progestins, progestins, there is no agreement among the several investigators.5•6•7•8•9) In our previous reports on the effects of progesterone and 沿ynthetic progestins upon the the uteri and the ovaries in rats and rabbits, it was shown that progestins caused some changes on the levels of phosphates and protein in the organ. However, it was difficult difficult to 白ncl a certain relation between protein metabolism in the organ and the biological biological potencies since the potencies of the progestins ・were so ample in variation and complicated. complicated. The present experiments ¥Vere designed to proceed the researches on the effect of pro- gestins, gestins, i.e., progesterone, retroprogesterone, megestrol ac 、etate (G-dehydro-G-methr1- l 7a-acetoxyprogesterone), ethynodiol diacetate (17 叶 ethynyl-1 D引 ortestosterone-B, 17 -di- acetate) acetate) and 19-norethysterone (17 昨 ethynyl-19-nortestosterone), upon the levels of the phosphates and protein in the ovariectomized rats uteri and to clarify the responsibility of the the biologic 、.al activities of the compounds for the changes of phosphate level 日 in uteri. * Dcpcrtmcnt of I》harmacology, Kyoritsu College of Pharmacy, (:i -Shibakocn, :'.¥linatoku ‘Toky け， Japan. Japan. 1) 1) Ui, H., and G.C. l¥Iueller, Proc. Aアαt. Ac α d. Sci., U.S.A. 50: '.2,:,li, l!Hi:l. 2) 2) 2¥Icans, A.R., and T.H. Hamilton, ibid., 56: G8G, lntiG. 3) 3) Gorski, J ., ]. Biol. Chern., 239: 88n, Hl64. 4) 4) Hamilton, T.H., C.C. ¥Vindrell and J. R. Tata, ibid., 243: -WS, 1!)!i8. 5) 5) Telfer, l¥LA., Arch. Bioc!tcni., 44: 111, 1%3. 6) 6) Borell, U ., A eta E ηdocrinol., 9: 141, 1%2. 7) 7) Lerner, L.J ., R. Hilf, A.R. T、urkeimer, I. Michel, and S.L. Engel, Jよnd υcrinology, 78: 111, HHi6. 8) 8) Brody, S., and A. ¥Vestman, Acta 1子ndoclinol., 27: 493, 1958. 。） Hallis, D.N., L.J. Lcr 肘 r, and R. Hilf, Trans N. Y. A cad. Sci., 30: i74, 1068. - 61- No. 1λ （］ f110) Materials Materials and Methods Female Sprague-Dawley rats, G 7-GO days old and weighing from 170- 1DO g, were used. used. They ,wre daily cxcrmined vaginal smear throughout the period of the experiment 吋 and m りre than one estru ぉ cycle were passed before the animals ・were placed on experi- rncnb. rncnb. Ovariectomy V¥'as undertaken under light ether anesthesia and the administration ()f ()f th ヒトtcroids v,a 日 begun ：？ ιhours after the operation. The experiments were designed to study the effect of a) consecutive administration of of progestins alone, and b) single injection of progestins after estrogen pretreatment. The animals ,wre given progesterone, retroprogesterone, megestrol acetate, ethynodiol di di acetate, 19-norethysterone as follows: a) Progestins were subcutaneously injected onceοn each of 4 consec 、utive days with daily doses of 0.25 mg in 0.2 ml of arachis oil and the rats were sacrificed 2壬hours after the last inJection. b) The animals were primed ，，江 h 30 pg of estradiol in 0.2 ml of arachis oil 日ubcutaneously, and received hypodermall:y ・ 0.2 ml of arachis oil solution which contained 500 μg of progestins 24 hours hours after the pretreatment. The rats were decapitated 2± hours after the last injection. To the control groups, the same volume of arachis oil were given. The uteri were removed and ¥'Veighed rapidly and as mentioned in the previous paper (10), (10), the right horn of the uterus was served for the extraction of phosphates, and the left left horn ,ms cut longitudinally into 2 parts, one harf of the 同 ctions, that is, one quater part part of the uterus, ,vas served for the determination of the protein concentration and the the υther 同 ction was employed for the estimation of dry weight. The details of the subsequent analy ちis of phosphates or protein vvere described in the previous paper.10l The detennjnations of anabolic-androgenic potency of the progestins were carried out acrordin 日to the method of Hershberger et al. (19G:1) _lll Results Results and Discussion Each phosphate level of the 5 fractions (acid soluble-phosphate, abr. p., inorganic-p., phospholipid-p., phospholipid-p., RNA p., and DNA-p.) in ovariectomized rats uteri are expressed as as P mg per 100 g dry tissue wieght and presented in Table l and 2. As seen in Table 1, ethynodiol ethynodiol diacetate caused an increase of acid soluble-p., inorganic-p., and RNA-p .. On the contrary, phospholipid-p. concentration was significantly increased with megestrol acetate. acetate. RNA/DNA ratio was significantly increased with 19-norethysterone, or ethynodiol diacetate diacetate and slightly increased with progesterone, retroprogesterone, or megestrol acetate. However, acid soluble-p., and RNA-p. were not a妊ected by the repeated administrations of of progesterone, retroprogesterone, or megestrol acetate. It It is well known that estrogen treatment enhances the synthesis of RNA in the uterus. As seen in Table 2, estradiol increased the levels of acid soluble p. and RNA-p. and RNA/ 10) 10) Kato, R., ::¥!. Kimura, and E. Nakamura, Ann. Report J{yoritus College of Pharmacy, 14: 43, 196H. 11) 11) Hershberger, L.G., E.G. Shipley, and R.K. Meyer, Proc. Soc. Exptl. Biol. 1Wed., 83: 175, 1953. - 62 ー No. 15 (l 970) ’l‘ able 1. Phosphate Levels in Uterus (Ovariectomizetl Rats) (mg/100 g dry tissue weight) 加。id iAcid Sol. -P. j lnorganic--P. [ Phf~~- ! RNA-P. _I 日NA-P ・ 1 RNA/DNA Control Control /191. 9土 7. 7 i 凶 9 土 8. 0 149. 5土13. 4 lns. 2土 1s. 1 I山 1±25. ~j 0. 48±0. 11 Pro 広estcrone 201. 0 士 2. 1 I 1-lJ. 0 士：； 1. 6 I ::i2. 2土 4. 7 1141. 3 土 s. 9I 229. 3 土11. 41 0. 62 土0.05 Retroprogestcro 川 203.6 土 19. 4: 155. 3 士 s. 1 I 70. 2土 9.6 1121.3 土1s. oI 230. 9 土30. 11 o. 53 土0.06 :'.¥[e 只estrol acetate 1203. 4土 9. 8 152. 7土 13.o I 74.o 土 0.8 判131. 5士 9. 4I 240. 3 土 9. 81 0. 55 土0.03 Eth vnodiol d iaceta te 230. 0 土12. 3* 185. 2 土 B.3 ＊水｜ 51. 2士24. 7 I 16:1. 3土 u. 9*1 198. 9土 16. 31 0. 83 こと 0. 11 キ 1U-Norethystcrone 224. 8土： 1l. 1 i 145. :1 士 1. 2 I 42. o土 7. 4 1157. 0土 19. 4I 221. s土 19. 81 0. 69 土0.04* );ote: );ote: 1） γotal doses of 1 mg injected (s.c.) once a day for 4 days '.l ）ホ Significantly different from control (p ，二 0.05) 事＊ Si 宗nificantlyιli 丘ercnt from control (p・ 、0.01) DNA ratio considerably. ¥Vhen progesterone, retroprogesterone, or lD-norethysterone were given after estradiol priming, above-mentioned e妊ects of estradiol were inhibited by those steroids. In the contrary, ethynodiol diacetate, or megestrol acetate were not able to inhibit the estradiol action. A similar decrease in uterine RNA of rabbits had been reported for progesterone by Brody and Westman.8) Phospholipid-p. concentr 仕 tion was slightly decreased by the administration of progesterone, retroprogesterone, or l 9-norethysterone in estracliol primed rats, but marked increase was observed with Table 2. Phosphate Le¥・el 円 in l:tcrus (Ovariectomized Estradiol--treatecl Rats) (mg/100 斥 dry tissue 1同 ight) Steroid Steroid I Hrs.I ・I Acid sol-P. IInorganic-P I Phospho RNA-P.
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