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

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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 progestins, 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. I DNA-P. RNA/DNA I I ・1 Iipid-P. I Control Control O 1217. 6土33. 6 1150. 1土20. 3 I 73. o土13. 6 1167. 8土22. 6 1217. O 土37. 010. 78 土0.04 18 18 1205. 6土21. 0 1153. 8士 13. 6 I 77. 3 土15. 4 1140. 5土 8. 5 1201. 7土26. 310. 71 土0. 12 24 1171. 5土 17. 4 1113. 1土 12. s I 88. 7 ごと 25. 6 1107. 3土 9. 6* 1165. 7土2t. 310. 66 土0.07 48 :200. 9土21.1 133.8 土 16. 8 i 70.3 土10. 2 1141. 3土14. 7 1181. 2土30.110. 82 土0.02

Estracliol Estracliol 18 i275. 4土50. 3 194:. 4土 14. 5* I 84. 3 土20. 7 1204. 5土 5.3 ＊本1182. 9土 6. 311. 12 土0.04**

, 24 1241. 6土 17. 1*1178. 8土 0. 8**i 66. 3 土 7. 2 1212. 1土22. 2**1182. 5土 5. 711.16 土0.01 ＊本 ¥ 48 1243.2±40.4 川78.1±43. 4 ; 88. 3 土 7. 6 1172. 批 22.0 jl82.2±27. 叩 95 土 0 06* Estradiol Estradiol primed progesterone progesterone 1226. 5土 10. 21162. 3士山！ 74. 佐川 I1山 15. 1 1211. 3土 4.610. 77±0.05"' Estradiol Estradiol primed Retro- /210. 3土 19. 0 1140. 1土 6. 3 ; 75. 0 土21. O 167. 8土 7. 5 1212. 2土11. 910. 79 土O.OP proge 自terone Estradiol Estradiol primed l¥Tegestrol l¥Tegestrol acetate 1240.8 土 4. 71173. 0± 6. 8 l…O l凶88.5 土山 1219. 社 8.81 Estradiol Estradiol primed Ethynodiol '213. 4 土 4. 7 :136. 4 土 10. 6 ,115. 1土 7.66 ム， 189. 1土17. 3 1179. 4土 2. 411. 00 土0.09 diacetate diacetate Estradiol Estradiol primed rn-Nor- )205.1 土 16.61151.4 土 10. 4 174. 8土山。… 11 0.06Ci. ethystcronc ethystcronc …… Xotc: 1) * Significantly different from control (p く0.05)

料 Significantly di 妊erent from control (p く0.01) 2) 2) t:. Significantly di 任erent from estradiol-treated rats

-63- No. 15 〔1970) ethynodiol ethynodiol diacetate. As reported above or previously, under any conditions と； tudied using normal, normal, hypohyzectomized or ovariectomized animals, the e妊ects of ethynodiol diacetate on acid soluble-p., RNA-p. or RNA/DNA ratio were similar to those of estradiol. No significant significant change was observed on DNA-p. concentration with any of these steroids. Mueller Mueller and his co-workers,12•13l and Dass et al.14l demonstrated that estrogen induced the increasing of RNA in uterus within 2壬hours, but DNA synthesis was occured 40 to 72 hours after estrogen treatment. This present result is out of ac- cordance with their result in the point of DNA. The disagreement may be caused by the the differences of the methods of administration and the doses. Estradiol Estradiol produced an increase in uterine protein contents (Table 3). This estrogen induced increases were suppressed by a single administration of progesterone, retroprogesterone, progesterone, or megestrol acetate. On the contrary, 19-nortestosterone derivertives; ethynodiol ethynodiol diacetate and 19-norethysterone, were more potent for the increaseing of total total protein contents in the estrogen primed ovariectomized rats uteri than estradiol

alone. alone. 19 場 Nortestosterone derivatives did not reduce the protein contents in the uterus, but rather intensified the effect of estrogen (Table 乃）．’ Table 4-5 illustrate the orga)l

Table Table 3. Total Content of Protein in ¥¥'hole Uterus

Ovariectmized Ovariectmized Rats Ovariectmized Eatradiol-Treatcd l{ats

Steroid Steroid Protein mg. Steroid Hrs. ! Protcm m ば・

Control Control 3.04 土0. 87 I Control o I 2. ss 土 0.37 18 18 3.08 土0.29 24 24 3.14 土0.07 48 48 2.70 土 0.42 Estradiol Estradiol 18 3.51 土0.52 24 24 3.87 土 0.30** 48 48 3.20 土0.46

Progesterone Progesterone I 35. 3土 O. 72 I Estradiol primed I I Progest r 2.95 土 0.40 Ret 均時叫crone I 3. 38 + 0. 51 I Estradiol pr ed 2.90 土0.29 ｜一 I Retroprogesteron Mege ol acetate I 3. 09 土o.38 I ~芯認己~~；~ 1e 2.90 土0.62 I I Estradiol primed E 向 rnodiol diac 向 te I 3. s01 土0. 79 I Ethynodiol diace 凶 e 3.46 土 0.31

件 Noretl 3.86 土0.49 斗

Note: Note: * Significantly di 妊erent from control (p く0.01) ム Significantly different from estradiol treated rats (p く0.05) weights weights when the steroids were given with or without estrogen priming. Without estradiol priming, priming, megestrol acetate or ethynodiol diacetate caused a marked increase in uterine

12) 12) J ervell, K.F., C.R. Diniz, and G.C. Mueller, ]. Biol. Chem., 231; 945, 1958. 13) 13) Mueller, G.C., A.M. Herranen, and K.F. Jervell, Recent Progr. in Hormone Rcsc α rch, 14: 95, 1958. 14) 14) Dass, C.::¥I.S., S. Mohls, and M.R.N. Prasad, Endocrinology, 85: 528, 1969. -64 - No. 1~5 (1970)

Table Table 4. Or ；ぷ l!1 "~eight of Ovaricctomiz 引 l h'.ats (mg/100 (mg/100 g body weight)

Adrenal Adrenal GI. Steroid Steroid T了teru 月

Right Right I Ri 符ht , Left i Right

Control Control 116. 2± 3. 8 (18. 0土 5. 3 !396 土 31 1390 土 29111. 9土 1. 4 ¥13. 0土 1. 8 Proges Proges teronc 77.4 土 10. 6 !11. 0土 7.0 116. 7土 6. 7 1405 土 35 !424± 46[12. 0土 1. 5 113. 0土 1.0 Retroprogestcrone Retroprogestcrone 78.2 土 8.4 14.6 土 5.2 113.9 士4. 2 f401 土 37 :339 土 27:11. 2土 1. 5 112. 2土 1. 8 ::¥Iege 日trol acetate [104. 6土 9 伊 114. 2±2. 5 14. 2±2. O 日26 土 32 '405 士24j s. s土 1. 1* I 9. 5±0. 9*

Ethvnodiol Ethvnodiol diacetate 169.3 土 17.3 料 il5. 8土4.5 17.4 土 5. 9 .427 土 18 叫04 土 26:1 幻土0. 7 114. 0土 1. O*

19 －又 oreth 円 terone 1 94.4±48.5 il0.5 土 3. 9* 9. 1土 2.5 料 379 土 24 368 士24 8. 7土 0.3 川 1.0 土 1.0 ネ

珂ote: 1) Total doses of 1 mg were injected (sι ） once a day for 4 days. Control: Control: total doses of 1 ml of arachis oil were injected (s.c.) for 4 days. 2) 2) * Significantly different from control.

Table Table 5. Ratio of Dry-weight to ¥Vet-weight of t;terus (Ovariectomize(l (Ovariectomize(l Rats)

Steroid Steroid Steroid Ratio I Ratio

cPRornottqbr’reod 0.239 土 0.024 Megestrol acetate I 0. 196 土0.011 料は mmu川 n et UF 0.224 土 0.018 Ethynodiol diacetate I 0. 195 土0.004 料

－ c mr淀 βivrAo n nu 0.219 土 0.023 Hl －文 orethysterone i 0. 199 土0.009 料

珂ote: 1) Total doses of 1 mg were injected (s.c.) once a day for ・4 days 2）村 Significantlyclifferent from control (p<0.01)

weight, weight, but progesterone, retroprogesterone or 19 同 norethysterone did slight increase (Tableι ）. Furthermore, megestrol acetate, ethynodiol diacetate, and 19-norethysterone significantly significantly reduced the ratio of dry/wet weight of uterus (Table 6). Thus, it is clear that that megestrol acetate, ethynodiol diacetate and 1仏norethysterone induced an increase

of of water concentration in uterus. However, in estradiol primed rats, progesterone, retro 叩

progesterone, progesterone, or megestrol acetate significantly reduced the uterine weight, but the weight 沿 were not able to returne to the control levels. Ethynodiol dia ℃ etate and 19-norethysterone did did not inhihit the estrogen induced increases of uterine weight 日（ Table 5). On the other

hand, the ratio of dry/wet weight in estradiol primed rats uteri were increased with pro 司 gesterone, gesterone, retroprogesterone, or 19-norethysterone, but did not increased with megestrol

acetate, acetate, or ethy ァnodiol diacetate, that iへwater concentrations in uteri were decreased with progesterone, progesterone, retroprogesterone, or 18-norethysterone, and did not decreased with megestrol strol acetate, or ethynodiol diacetate (Table 7). Anabolic and androgenic activities of these progestins exermined in castrated weanling male rats arc shown in Table 8. No significant changes in levator ani, seminal vesicle, and prostate were observed by the consecutive administration of total doses of 1.5 mg - 65 - Ko. 15 (1970)

Tabl ℃（ i. < lr 以an ¥¥.eight of (h・aricctomizcd Estradiol-Trcatccl Rats

(mg/ 100 只l州 ly ¥¥i 山 ht)

EE、， 4Ll 4 ‘i γιぐl、，1 1 1ι’l ・、X 川町［人drenal Cl. Steroid Steroid Irι ．： l tじl Ll 、

Right ・ Ix 、lt ]{ight I Left : Ei 計1t , Left

Control ！（）（凶 8 土 19. -l 17. 3 土 3. 1 :17. 1土 3. 8 ;482±39 ¥496 土 35 )1s. o士 1.5 ¥16.8 土 1. 8

I 1s 1s4. ，土 21.5 p.6 土 3 』 20. 6 士3.0 1425±32 !421 土 12 113.5 土 1.0 [15.1 土 1. 0

I 24 ,1 札 9 土 14. 1 i1'・ 9 土 3. 4 22. G 土 6. 0 435 土 17 1412 土 17 110. 8土 0. 9 111. 6 土 1. 2 48 116. 8 土 18. 9 16. 8 土 2. 9 16. 2 土 2. 7 i412 土 58 1416 土 31 110. 5 土 1.0 111. ，土 1. 1

F:--tradiol F:--tradiol 18 ?53. 9 土 -iJ. 4料 113. 0 土 6. 2 12. 9 土 6. 4 :351 土 21 料 1333 土 31**110. 4 土 0. 5*?1. 2 土 1. l料

24 248. 3 土 15.8 吋 18. 1土 3. 3 .20. 6 土 6. 5 377 土 20 料 1384 士31 / 8. 1土 l.1*19.7 土 1. 7

48 171.7 土 30.3 料 16. 1土 4. 3 17. 1土 4. 1 j420 土 75 1-126 土 64 :12. 3 土 1. 8虫 113. 5 土 1.6*

E 旦tr 孔【 Uolprim じd 139. むこ 22.0 へ 22. l士 6. :'i6 23. 6 土 5.0ρ ！＼ 389 土 34 [382 土 31 13. 4 土 1. 3 :13. 9 土 l.6 I》rogcsterone Estradiolprimed Rctropro ｜山山い J7. 目 9 ;18. 3 士3.4 .393 士35 1394±-10 111. 山 8 i山 1. 2 gesterone ,

Estradiolpri 町 d ! l¥fegestrol l¥fegestrol acetate ' 132.6 土 32. 76 17. 4 士：－ L 8 17. 2 土 3. 3 382 土 33 !372 土 32 11. 4 土 1. 7 ,12. 7士 1. 9

Estradiolprimecl Estradiolprimecl ! Ethvnodiol i 169. 1土 17. ・± 14. 2 土 3. 8 11. 2±3. 3 396 土 33 396±23 112. 5 士二 1. 2 ;13. 4 士1.4 di 弘cetate I Estracliolprimccl Estracliolprimccl ; rn-Korethy- I 196.6 土 20. 6 21. 9 土 5.6'"22.9 土 7. ：）与 i,119 土 23 419 土 29 B・6 土 0.6 114. 6 土 0.9 はerone [

Note: 1) * Significantly di 白： crent from control (p く 0.05)

村 Signiacantly cli 百crent from control (p く 0.01) 2) 2) 6 Significantly different from estracliol treated rats

1EA》‘、 FfATI）唱＋ IdVO4a －－一’ dMezt ιι（ ri屯 H1ta ρlνnu川町↑九ぜ唱’HbTInt a 。、．，J －ー、 ci180 Loc JZ 、．可CrAPuS Table 7 J 旬、

rA．，、日一北一叶一江一 Kdー｝引lhA AVi L 一一↑で一一ハリハ泊一五い口一、 a 一一一・・・・・・一一一一壬一・一凶一土土土＋一土土士土＋一土？？一斗一一．一（－ Il －－ U0000000000OO Steroid Steroid ，』m － Illi 0848848000000000000222211111112331796874341000000000000TiAV076711393371 （、 ontrol 124124 －－ vtinυqu illl1111i 内リ

Aυ1iqatiAVA

＊＊・ネ＊＊＊今 Estracliol Estracliol つ dQUQUQUQUQU1a

44 Estracliol Estracliol primed Progesterone Estradiol Estradiol primed Retroprogesteronc リハ Estradiol Estradiol primed l¥1εgestrol ace ta tc V υ凡 Estradiol Estradiol primed Ethynodiol cliacetat ぐ Estradiol Estradiol primed 1H-K oreth ysteronc ハリ止

Note: 1) * Significantly different from control (p く 0.05) ** Signifidatnly different from control (p く 0.01) 2) 2) 6 Significant ］予ア di 日ercnt from estradiol-treated rat バ

-- 66 - No. IG (1D70)

Table 8. Anabolic Act ion and Other,;; (mg/100 g body weight)

Urgan Se1ninal Leva tor 人ni I{idncy I》rostate I Pr;P.ut;al Steroid Steroid Vesicle Gl.

Control Control 23.9 土 2. 9 I 951. 3 土30.6 11. 3 土 3.8 13.4 土3.1 I 19.1 土 7.6

PRMEHhmdgreomは戸町IoodJuvmvlT43J 1e 25.8 土 6. 9 I 878. 1土63.5 13. 1土 2.7 14.3 土5. 7 18.5 土 7.9 白血mneh 叫す 28.1 土 2. 4 I 90・L o土29.3 7.5 土 2.9 12.0 土 1.3 10.0 土 1. 4 時曲目巨叫ん’剛山； VAXH、コ、 27.8 土 4. s I 993. 1 土58.6 13.7 土 2.1 1-1. 2 土2.5 22.5 土 10.0 胃 D 小川陀41 EYAな’バmm旧aA L ρU 31. 31. 1土 2. 9* I 962. 9 こと 73.7 17.9 土2.5* 2・1. 2 土 7.6* 26.1 土 2.1

h宅、，ぬ九 JF Jw I 38. 7 ± 10. 4* j 877. 社 38.7 23.6 土 4.5 ホ＊ 29. 1土 7.0* 25.3 土 4.3

Note: 1) ＊ Significantly di 妊erent from control (p< 0.0,>). 2) 2) Total Doses of 1.5 mg ¥¥' a百 injected (s.c.) once 九 day for 6 days in in ca 日tratcd weanling rat （日－ D strain).

！1 x ．

’d ，，，，／〆〆，， F，，，，，，，4 1.0 1.0 〆，〆 J A ／，，〆／ XX 〆〆〆〆〆〆〆〆，，《 quauド，， zooIlillit J ，，， a， f 〆・〆ト《之，，，，〆〆企叫〆 AM 〆〆－－〆， αHhOO 〆 ILI ，，〆－－’’・〆，， ohEU，，〆〆－－，，〆 A 』』「司区v a 〆・〆晶＆／ Y = 0.0028 X 土 0.72 〆

〆 R = 0.95 8 本〆．〆，， ,7 ,7

.6 .6 20 20 40 60 80 100 120

EsTROGEN1c Arnv1TY 門G/IOOG B.W. ( UTERUS WEIGHT INCREASING EFFECT) Fig. Fig. 1. Correlation between Ratio of R:N"λto DN.-¥ and Estrogenic Activity :N" :N" ote: 1) • Progesterone ，ム:l¥Iegcstrol × Ethynodiol, 0 Iミetroprogcst じrn 、 O Retroprogestcrone .4 ‘1¥) 巴 norcth ystcron e ． 21* 21* Significant (p く.05) of progesterone, retroprogesterone, or megestrol acetate to the castrared rats, but marked

increase was seen with ethynodiol diacetate, or rn 四 norethysterone.

-67- No. lδ (1970)

It It is very difficult to gi¥・e a difinit explanation of the relationships between RNA, RNA/ DNA ratio, water and protein contents from these results. These progestins are not only only progestational but aL.;o estrogenic, androgenic, and anabolic activities. Table 8 shmvs the results of these activities. Among these potencies a correlations ¥Vere noticed

between the estrogenic potency and the RNA/DNA ratio v. アhen these progestins ¥¥・ere given given after estrogen primi 昭（ Fig. 1). However, all these experiments were carried out on the uterus which contains all the layers layers including endemetrium. So the experiments is now under the way to make clear the the relations using endometerium.

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