Title EXPERIMENTAL STUDY OF MALE PRECOCIOUS PUBERTY …repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/206748/1/ngh028001_158.pdf · Boy, 9 >・ca rs 4 months old, clearly manifestating

Title EXPERIMENTAL STUDY OF MALE PRECOCIOUSPUBERTY CAUSED BY CHORIONIC GONADOTROPIN

Author(s) YOSHIKAWA, SHIYOZI

Citation 日本外科宝函 (1959), 28(1): 158-183

Issue Date 1959-01-01

URL http://hdl.handle.net/2433/206748

Right

Type Departmental Bulletin Paper

Textversion publisher

Kyoto University

158 日本外科宝函第28巻第1号

EXPERIMENTAL STUDY OF MALE PRECOCIOUS PUBERTY CAUSED BY CHORIONIC GONADOTROPIN

b~·

SmYozr YosHIKAWA

From the First Surgical Division, Kyoto Uni,・ersity Medical School (Chief Prof. Dr. CmsATO ARAKI)

(Recei,・ecl for Publication Jun. 22, 1956)

I INTRODUCT10N

For the explanation of the precocious puberty associated with a pineal tumor, the ontogenic theory was advocated lη λsKANAZY in 1906. He experienced a case of chorionepitheliomatous teratoma in the pineal region accompan>・in江 theprecocioug pubert>・ and presumed that the precocic〕us puhcrt:-・ might be due to the secretion of the gonadotropin-like substance from the chorionepithelioma. Thereafter, many unfavorable arguments were made, so that this theory has been almost ignored.

In 1957, FuKusHIMA of our laborntor:-・ histologicall≫ examined four brain tumors with precocious puber匂’ three pineal tumors (two of them were evidently teratomas) and a teratoma in the h≫pophyscal region, and found that the twoぱ

the three teratomas contained the chorionepithelioma-like tissue, and the third one contained a c.,・totrophoblastoma-like tissue. :.¥IoreoYcr, in a part of the remaining non-teratomatous pineal tumor, which was for the most part pinealoma, there were adenomatous or canalicular structures, ~.uggesting the possibility of teratoma. Thus, of the four tumors mentioned above, three had the tissue that might produce chorionic gonadotropin and also the remaining one (larg-cl≫ pinealoma) had a possibilit.'・ to be partly teratoma, so that as far aぉ ourcases are concerned, the precocious puberty would possibly be explained b>・ the ontogenic theory, i. e. by the chorionic gonadotropin which ¥¥・as secreted from the chorionepithelioma-like tissue within the teratoma. The most illustrative case will be briefl~・ described in the following.

Boy, 9 >・cars 4 months old, clearly manifestating precocious puberty; the 日econclm目ysex characteristics were clcγeloped conspicuousl＞’（public hair was gro¥1」

ing-, penis large and glan日 penisbared).

The bo.＇’was 129.5 cm tall and weighed 24 kg, i. e. in normal range. The gonadotropin in the urine measured with the kaolin adsorption method

just before death was found to be considerably increased, the value being 24・48m.u. u./24 h ..

人UTOJ>SYFINIHKGS：・＼＼・efound a teratoma in the h,,・po1巾〉河川 regionwith a chorionepithelioma-like tissue in a part. In the lung there were multiple metas・ tases of chorionepithelioma. The histological finding of a imrtion of the main Lumor invading the pituitar＞ア日talkwas similar to a pinealoma, and the h.¥・pophysis, being examined 川町I泊1sectionへwas completeb’ replaced l乃 thetumor with no

EXPERIMENTAL STUDY OF MALE PRECOCIOUS PUBERTY 159

remaining anterior lobe cell. In the testes LEYDIG cells were h~’perplastic hut germ

cells were atrophic and no spermatozoon was observed. In this ca叩，theamount

of gonadotropin in the urine was considerably increased in the absence of pituitary

anterior lobe cells, so it could not but be considered that the increased urinary gonadotropin had its origin in the chorionic gonadotropin which had been secreted

from the chorionepithelioma-like tissue. Therefore, it can be ・assumed that in this

case the chorionic gonadotropin secreted from the tumor probably induced precocious

puberty.

Thus in the present experiments, I administered in the first place a preparation

of puri白edchorionic gonadotropin to immature male rats in a dosis which was

roughly estimated from the urinary value of gonaclotropin in this case and from the ratio of body weight between man and rat, and in the next place I adminis-

tered a I~·ophilized powder of chorionepithelioma in the same way, in order to

investigate the experimental production of precocious puberty.

II -METHOD OF EXPERIMENT

1) Experimental animal: -Male rats of the same litter were used; they were

weaned three weeks after birth and isolated, and each was fed with the same

amount and the same kind of food. 2) a) As for chorionic gonadotropin, Primogonyl, the extract of urine of

pregnant women, made by Schering Co., was usecl. b) Lyophilized powder of the chorionepithelioma were gained from the

tumors in the following two patients.

i) Female, 41 years old.

Clinical diagnosis ：聞 Chorionepitheliomawith metastases.

Histological diagnosis ：・ Hydaticlmole.

ii) Female, 16 years old. Clinical diagonsis：・ Teratomaof the ovarium. Histological diagnosis ：・ Chorionepithelioma.

From the fresh tumor tissue at the time of autopsy, lyophilized powder was

immediately made.

3) Method of Administration：ーa) Every day 30 I. U. of Primogonyl were subcutaneously injected to rats

of five clays after birth. b) 10 mg lyophilized powder of chorionepithelioma emulsified in physiolo-

gic saline solution was subcutaneously injected three times a week to rats of five

days after birth. As a control for a), physiologic saline solution was injected under similar

conditions; as controls for b), lyophilized powder of cancer of the uterus and that

of the normal placenta were administered. Experimental animals were weighed weekl~· and then sacrificed 4 weeks (33

cla~·s after birth) or 8 weeks (61 clays after birth) after the beginning of admi-

nistration, and their sexual and other endocrine organs were weighed and histologi-cally examined.


III・RESULTSOF EXPERIMENT

A. ADMINISTRATION OF PRIMOGONYL

Nineteen male rats of seven litters were divided into two groups, one of which

was administered Primogonyl for 4 weeks and the other for 8 weeks respectively. 1) BODY GROWTH：” No di百erence was found in the lengths of the body

and tail in comparison to those in the control groups (Figs. 1 and 2). As regards

the increase in bod:-・ weight, if the rate of increase (the increased l川 h’ weight

divided b:-・ the body weight at the commencement of the experiment) was consi-

dered, this rate in the 4・weekPrimogonyl group wa日 7.45,while that in the control

group 7.04, and that in the 8-week Primogonyl group was 18.11, while that of the control group 17.65. Namelyア in the Primogonyl groups the value was a little

high, but when a comparison was made as to the mcrease in body weight per cla~＂

no significant difference was found between the Primogonγl and the control groups (Table 1).

Table 1. Body Weight of Primogonyl Administered Male Rats. (g)

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2) SE:Xl1AL DEVELOPMENT: The group to which Primogon:yアlhad been

administered for 4 weeks, indicated a more distinct sexual development as compared

with the control group (Fig. 1). l¥"amely, in the former, earl:-- development of

the scrotum and penis were seen and the te刈邸 descended into the scrotum in

about 16 da:--s after birth. But in the latter descensus testis waぉnot:-・et completed

even 30 r1何百 afterbirth. In the Primogon:--1 group the testes and especially the accessory sexual organ日 dist inc tl:--increa呂町lin weight and size and the glans penis

took a l"-t:-・pc (mature type) 29 da：－’只 after birth, whereas in the conti叫 group

EXPERIMENTAL STUDY OF MALE PRECOCIOUS PUBERTY

Fig・. I合 54 Rat No. 54 Male Rat Administered Primogonyl for 4 Weeks (33 Days after BirthJ.

合 55 Rat No. 55 Control :¥!ale Rat (33 Days after Birth).

161

this still showed the type of a V or W (immature t~·pe) even 33 da~・s after birth

(Table 2).

The weight of the penis in the Primogonyl group waぉ0.13g, i.e. the average

weight in mature rats and was about 2.4 times as much as that of the control

group. The testes were 1.13 g which was a little more than those of the control

group, while the epidid~·rnid引， prostate and seminal vesicles indicated a distinctly

early development with an increase of approximately 2 times, 4 times and 19 times

respectively in comparison with those of the control group.

In the 8・weekgroups, the penis of the control group also showed the U-type

(mature h’pe), but the accessory sexual organs of the Primogonyl group showed

much more increases in weight and size (Fig. 2). Yet, as compared with the

di百erencein the 4・weekgroups, the di百erencebetween their weights in the Primo-


Fig・. 2 合 33 Rat 1¥o. 33 :¥!ale Rat Administered Primogonyl for 8 Weeks (61 Days after Birth).

合 34 Rat :¥o. 34 Control Male Rat (61 Days after Birth〕．

広on~· ！ group and those in the control group was lesser in degree. l¥amely, the

weight of the penis was 0.22 g, i. e. approximate！~’ 1.4 times as n, uch as that of

the control group, and the weight of the testis was about the same as that of the

control group, hut the epidi【lymis,prostate and seminal vesicle ＇＇’ere approximately

1.4, 2.8 and 3.0 times respective！~· a日 heavya只 thoseof the control group (Table 3）・

3) The weight of the hypoph~吋日， thyroid gland and adrenal gland of the

4・week(Table 4) and the 8・week Primogon:d (Table 5) group indicated no diffe・

rence in comparison with those of the control group.

HISTOLOGICAL FINDINC:S

1) TESTIS : In the叫凶mentalgroup which ¥1・; administer帽ed Pr og仰

for 4 week日， cli日tinct 11~ · pe1、pla：只ia of LEYDIG cells in the inter、stitial tissue, ana

EXPERIMENT AL STUDY OF MALE PRECOCIOUS "PUBERTY 163

Table 2. Weights of Sexual Or・gansand Their Ratio to Body Weight in Male Rats Administered Primogonyl for 4 Weeks.

－ ' 〆3

*・・・Weight of Bilateral Epid.・・・Epididymides Prost.・・・Prostate Organs Sem. Ves.・・・Seminal Vesicle

Table 3. Weights of Sexual Organs and Their Ratio to Body Weight in Male Rats Administered Primogonyl for 8 Weeks.

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numerous spermatocytes in the seminiferous tubules were found, but in the control

group such changes were not noticed (Fig. 8, A, E). In the 8-week Primogonyl

group, though there was no distinct difference in the weight of the testis as com-

pared with that of the control group, distinct hyperplasia of LEYDIG cells was seen

in the interstitial tissue. Numerous spermatocytes were noticed in both the Primo-

gonyl and the control group (Fig. 9, A, F).

2) As regards the thyroid gland, adrenal gland and pineal body of the 4-week

and 8・weekgroup, there was no di百erencein weight and in the histological finding

to note between the Primogonyl and the control group.


つ竺二

三三IJX. L二五lXlV

Table 4. 羽Teightsof Hypophysis, Thyroids and Suprarenals and Their Ratio to Body Weight in Male Rats Administered Primogonyl for 4 Weeks.

:r」itter・ N口. Bo《I~’ ｜羽＇eight (g) ・ Ratio to Body Weiεht (g/gx 10 0 ）

i~~~s J一一＂；~＇ v I 29 I 97 I 0.0045 I O.OH : 0θ21 I 0.0046 I 0.014 I 0.02 l Vil I 36 i s5 I 0.0036 ¥ 0.012 I 0.023 I 0.0042 ¥ 0.014 1 0.021

' 37 I n I 0.0042 I 0.011 I o.ors I 0.0058 I o.ors I o.ozs 54 I 98 I 0.0033 I 0.014 I 0.019 I 0.0033 I 0.014 I 0.019 92 I 82 I 0.0029 I 0.011 I 0.021 I o.0035 I 0.013 I o.02s

山 j 0.021 I 0.0041

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0.0037

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0.014 0.023

0.020 0.030 0.013 0.027 0.014 0.026 0.012 0.030 0.012 O.D28

0.014 O.D28

Mean Value 86.8

0.0037

0.019 0.029 0.0044 0.011 0.024 0.0047 0.012 0.023 0.0047 0.013 0.031 0.0034 0.010 0.022 0.0038

0.013 0.025 0.0042

＊．羽Teightof Bilateral Or巨ans

Table 5. Weights of Hypophysis, Thyroids and Suprarenals and Their Ratio to Body Weight in J.¥Iale Rats Administered Primogonyl for 8 Weeks.

Litter ; No・ Body : Weight (g) : Raio to Body Weight(g/g×100) I 1Weig:ht:

Rね｜！（ぷ向。phy判 Thyroids本 jsuprarenal;,Hypo向川町y州 sJsupraren拙

I I 3 I 174 I 0.0012 I 0.016 I 0.034 I 0.0041 I o.oo:i1 I 0.019 I 4 I 196 I 0.0066 I O.Dl5 I 0.030 I 0.0033 I 0.0076 I O.ot5

JI I 11 I 136 I o.0044 I 0.016 I 0.030 I 0.0032 I 0.0111 I 0.021 I 12 I 155 I 0.0055 I 0.014 I 0.023 I 0.0035 I 0.0089 I 0.014

VI I 33 I 192 I o.ooso I 0.020 I 0.026 I 0.0025 I 0.0104 I 0013

Mean Value 170.8 0.0057 0.016 O.Q28 0.0033 0.0095 0.016

ーコ【 I 6 194 0.0062 O.Dl5 0.031 0.0031 0.0077 0.015 【 7 180 0.0070 0.014 0.026 0.0038 0.0075 0.014

Vt I 0.0067 0.022 0.027 0.0042 0.0138 O.ot8

'-' ~ 34 206 0.0065 0.022 0.036 0.0031 0.0106 0.017 一一一

Mean Value 184.5 0.0066 O.Dl8 0.030 0.0035 0.0099 0.016

*・ .. We¥ght of Bilateral Organs

B. 人H:.¥rI:t¥ISTR人TIO:'¥OF CI-IOIUO:¥'EPITIIELIO::.¥!A LYOPHILIZED

POWDER

Forty-six rats of twcl\'C~ litters ¥I’ぐl℃日cparatcdinto two groups and the lyophi-

lizecl powders pro:luc-c:l from chorionepitheliomas in two patients mentioned above

were administered to each experimental grou11. The tumor i) ¥¥'as used for cxper卜

mental group I ancl the tumor ii) rけrexperimental group II.

1) BODY GRO¥¥"I、日：ー In both the experimental group I and II there was

no difference in the lengths of the IJOtl,¥ and tail as compared with the controls

(Figs. 3, 4, 5, 6 and 7). /'l.s reganls the i11 cn~a sc in bod~· weight, i. c. the rate

of increase and the increase of ＼＼℃ig-ht per d川’ inboth the cx1〕erimentalgroups I

and II, no di町erencewas noticed as compared with those of the control groups

165 EXPERIMENT AL STUDY OF MALE PRECOCIOUS PUBERTY

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Table 6. Body Weig-ht of l¥Ialc Rats Administered Lyophilized Chorionepithelioma and Placenta Powder. （ε〕

3.2 2.8 3.0 2.9 3.0

2.98

つ’U1A。，uqδ勺δっο

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134: 11.0 29 82 71.0 6.45 2.5 132 10.0 29 68 58.0 5.80 2.0 48, 8.5 28 78 192 69.5 183.5 8.17 21.47 2.4

! 65i 10.0 26 68 186 58.0 176.0 5.80 17.60 2.0 ; 88 9.5 35 86 190 76.5 180.5 8.04 19.00 2.7

をxv引i空xx0 x:x田空 XX!l;::: v川~ x 己 Xll

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189.3, 67.7同司6.92I 19.35!

that a

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(Tables 6 and 7). ?dorcovcr, it seemed right to assume has no e百ecton body growth, as shown in the Table 8.

SEXUAL DEVELOPMENT

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nwu ハ’’uMean Value 9.8

mean value of the weights of the

much as that in the controls,

2)

Similarly to the previous experiment in which Primogonyl ＼＼・asadministered, the administration of the lyophilized powder of the chorionepithelioma brought about an earl＞’ development of the sexual organs. Namely, in the experimental group I of 4・weekadministration, there was a distinct di百erencein the development of the penis, scrotum and the other accessory sexual organs as compared with those of the control group (Fig. 3). In this group the glans penis took the mature U-t≫ i〕ein about 3-l cl川’日 after bit廿1 while in the control group the U-type of

glans penis took place approximately 50 days after birth. In the group where lyophilizecl powder of a malignant tumor was administered,

no sexual precocity could be noticed.

In the 4：恒＼ ck chor

penis was 0.105 g, i、e. approximately 2 times as


Table 7. Body W巴iεhtof Male Rats Administered Lyophilized Chorionepithelioma

Powder. I日）

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Tahle 8. Body Wei耳htof 1¥Iale Rats Administered Lyophilized Chorionepithelioma and Cancer Powder. (g)

叫ん一主

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but as for the tcト；tis,it was 0.36 g, i. e. 0.41 times as small as that in the control

group, but the ncccss01下 sexualυrga11日， 11れrncl.'the epidid~·mis, prostate and semト

nal vesicle were approximately 1.5 times, 2.8 times and 5.8 times respectively as

much as those in the control group (Table 9). 1

In the 8-week chorionepithelioma group the a vcrag-e weight of the penis was

EXPERl'.¥:IE0;TAL STUDY OF MALE PRECOCIOUS PUBERTY

6 120 ぢFig-. 3 -CS 120 Rat No. 120 Male Rat Administered Chorionepithelioma Lyophilized Powder

for・4Weeks (33 Days after Birth). 合 121 Rat No. 121 Male Rat Administered Placenta Lyophilized Powder for 4

Weeks (33 Days after (Birth). 合 122 Rat No. 122 Control Male Rat (33 Days after Birth).

167

0.181 g, i. e. rather large in comparison with that of the controls, but the testis was 0.63 times as small as that of the controls. The epidid~·mis was also rather

small, but the prostate and the seminal vesicle were 2.3 times and 1.9 times larger respectively, the di百erencesbeing not so remarkable (Table 10).

The result of experimental group II was about the回 meas that of experimen・tal group I, but the di庁erence in comparison with the controls was more promi-

nent (Figs. 6 and 7), the glans penis took U-t;:pc about 30 da~・日 after birth, i. e.

more quick！~’ than approximate 43 cla~·s after birth in the controls. In regard to weights of the sexual organs, the penis of the 4・weekchorion-


会82 ~ ・・=. くご3て

Fig・. 4 合 82

合 84

合 88

二薗幽醇輯醐闘臨＿，＿

Rat i¥円.82 Male Rat Administered Chorionepithelioma Lyophilized Powder for 8 Weeks (61 Days after Birth). Rat No. 84 '.¥Tale Rat Administered Placenta Lyophilized Powder for 8 Weeks (61 Days after Birth). Rat No. 88 Control Male Rat (61 Days after Birth).

epithelioma group was 0.115 g, i. e. approximate！~’ 2 . 3 times larger than that of the controls, the testis was 0.36 g, i. e. about 0.48 times smaller, but the epididymis,

prostate and seminal vesicle wc1℃ approximately 1.5 times, 3.8 times and 5.6 times

respectively larger than those of the controls, the difference!:' being remarkable (Table 11).

In the 8-wcck chorionepithelioma groups, the penis weighed 0.185g i.e. larger

than that of the controls, whereas the testis was approximatcl:-・ 0.54 times 日mailer

than that of the controls, but the prostate and seminalγcsicle wc1℃ approximately

3 times larger than those of the controls (Table 12).


i Fig-. 5 -0 45 Rat No. 45 Male Rat Administered Chorionepithelioma Lyophilized Powder

for 8 Weeks (61 Days after Birth). 会 47 Rat No. 47 Male Rat Administered~Cancer~Powder for 8 Weeks (61 Days

after Birth). 合 48 Rat No. 48 Control Male Rat (61 Days after Birth〕．

169

Thus, a decrease in weight of the testis was seen in the rats administered

lyophilized powder of chorionepithelioma, and similar decrease was also found,

though to a lesser degree, in rats administered lyophilized powder of the placenta.

But with the use of lyophilized powder of a malignant tumor such a decrease could

not be observed. Therefore, it is supposed that this change is caused by the inftu-

ence of the chorionic tissue.

Moreover. it was found that the administration of lyophilized powder of a

malignant tumor caused no variation in the weight of the accessory sexual organs.='.

(Table 13）・


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Fig・. 6 合 219 Rat l¥o. 219 Male Rat Administered Chorionepithelioma Lyophilized Powder for 4 Weeks (33 Days after Birth).

合 220 Ratト＇＇°・ 220 Control Male Rat (33 Days after Birth).

171

3) In both experimental groups I and II, no change was noticed in the

weight of the hypophysis, thyroicl gland and adrenal gland as compat℃cl with the

control group (Tableメ 14,15, 16, 17 and 18).

HISTOLOGICAL FINDINGS

1) TESTIS: -In the 4-week chorionepithelioma group of the experimental

group I hyperplasia of the LEYDIG cells was noticed, but less remarkabl~· than that

taking place in Primogon~·l administered rats. Germinal cells were more atrophic

than the control group and no spermatozoon was found (Fig. 8，ぐ）．

In the 8・weekchorionepithclioma group, LEYDIG cells hyperplasia was much

more distinct, but germinal cells did not differ from those of the control group.

172 日本外科宝函；第28巻第1号

Fig・. 7 合 184 Rat No. 184 Male Rat Administered Chorionepithelioma Lyophilized Powder for 8 Weeks (61 Days after Birth).

合 185 Rat No. 185 Control Male Rat (61 Days after Birth).

Many spermatozoa were noticed in both groups (Fig. 9, C). By the administration of the 1~·01〕hilized powder of the placenta or of a mali・

gnant tumor, no marked change took place in the LEYDIG cells and germinal cells (Fig. 8, D and Fig. 9. D).

Experimental group II. The changes in weights of the sexual organs were more prominent than those of experimental group L and histological ex乱mination revealed that hyperplasia of the LEYDIG cells were more distinct than that in experimental group I. As was expected atrophy of germinal cells was found in the 4-week chorionepithelioma group and no spermatozoon was found in seminiferous tubules (Fig. 8, B).

In the 8・weekchorionepithelioma group, spermatozoa wer~ found similarly切


Fig・. 8 The testis in Rats Administered Primogonyl and Lyophilized Chorionepithelioma and

Placenta Powder for 4 Weeks and Control Rats (33 Days after Birth l. Hematoxylin-

Eosin Stain x 150

A. Primogonyl Administered Rat No. 5-1. B. Chorionepithel ioma Lyophil ized Powder

Administered Rat t¥o・219

173

C. Chorionepithelioma Lyophilizecl Powder

Administ巴redRat No. 120

D. Placenta Lyophiliz巴dPowder Administered

Hat No. 121

E. Control Rat No. 55.

17-1 日本外科：:ii:i'J'r :;(\ "28 ~会第 1 号

Fig・. 9 The testis in !{al凶AdministeredPrimogonyl and Lyophilized Chorionepithelioma,

Placenta and Cancer fo1・8Weeks and Control Rats <61 Days after Birth1.

Hematoxylin-Eosin Stain x 150

:¥. Primo日011,・J"l.¥t!111 in i日le1・cd lじlL'¥n. :n. B.、’Chりl"iり11cpilhclio111aLγOJ〕hilizcrl Powder

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上；. Caneer Lyuμhili辺ec.l.Powder Administered F. ( 'unlrol Rat No・34.Rat No. 47.


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Table 12. Weights of Sexual Organs and Their Ratio to Body Weig-ht in Male Rats Asministered Chorionepithelioma Lyophilized Powder for 8羽Teeks.

Litter No・IBodv JT~J)e of! w均 ht(g) : Ratio to Body Weight (g/g×100) IWei ht I, r-ems 一一一「一一 1一一－，一一一一 I I I I （~~h '(Age Penis 1Test白 ~jEpid."'IPr姉除去 Pen叫 Testes ~Epid . P附 1i~~·I 6 I Day) I I I I : I : I !

·~m Q.iXXVDJ I 174! 168 I U(3Q) I O.叶 i.02I o.37 I 0.61 I 0.62 I 0.1パ 0.60I 0.22 I o.36 I o.36 § E 51 ! 1751 164 I U(31) I 0.1881 1.08 I 0.33 I 0四 Io.69 I ~·！日 o.6s I 0.20 I o必 I0.41

・c.S~』： 1761 174 I u C30l I 0.1831 i.01 I o.34 I 0.10 i o.68 I 0.10 I o.s8 I . I . I e~ ＇＂＇ 1xxoc 1 I刊日 IU(30〕Io.吋 1.32J o.36 I o.64 I o.67 I 0.1川 0.75I 0.20 I 0.36 I 0.38

－；よ~Value l刈（ふ－斥1851 1.10 I o.35 I o.67 i o.s可石可ち Jxx咽 I1吋 180 1J（州 0.1551 1.96 I 0.41 I 0.28 ! 0.23 I 008 i 主苫｜ I 118j 166 Uけ2) o.1s2 1.97 I o.38 : 0.11 '0.21 I o.o9’ ~ 21 I 179' 163 Ur 15l o.1soi 2.07 I o.37 i 0.24 0.23 I 0.09 001xxix 11倒閣 U日5)' 0.1叫 2.18I 0.38 I 0.19 ! 0.18 I 0.08

I Mean Value 112.2 f (43) I 0.叫 2.04I o.38 I 0.22 I 0.22 I 0.08 I ＊…Weight of Bilateral Epid. ・・Epididymides Prost ... prostate

Organs Sem. Ves. ・Seminal Vesicle

o.64 J 0.20 !

司司

0.15 I 0.12 0.10 I 0.15 0.14 I 0.15 0.10 I 0.10

the control group, but LEYDIG cells hyperplasia was more distinct than in the

control group (Fig. 9, B). 2) In regard to the thyroid gland, adrenal gland and pineal body, no marked

change was found in both experimental group I and II.

C. COMMENT

In summarizing the results obtained in our experiments, it can be said that

by administering Primogonyl and lyophilized powder of chorionepithelioma to im-

mature male rats, though earl;: somatic development did not occur, earl~・ develop

ment of the sexual organs was noticed. Namely, by・theperiod when rats normally


Table 13. ¥¥'eights of Sexual Organs and Their Ratio to Body Weight in Male Rats Administered Chorionepithelioma and Can<:!er Lyophilized Powder for・8

羽Teeks.

Littρr ~o. Bo山Iv iτ司とpeof] Weight l ~〕一一一］ Ratio to Body Weight (g~~× l 0 0 ）

ふ W♂）；t: c足；is~~ ：l Testes jEpid.*il Day), I Iγ l I

z司号明｜ 4ユ 216 I r, clJ 1 i 0.205¥ 1.67 I 0.46 I o.64 I o.n I o.o9 I o.75 I 0.21 I 0.29 1 o.33 5主。）［ sり 189 t: I 33 I 0.1811 1.39 I 0.36 I 0.54 I 0.30 I 0.09 I 0.72 I 0.19 I 0.28 I 0.15 E三ヨ－ 60. 175 i U1 :371 I 0.1711 1.32 I 0.34 I 0.53 I 0.30 I 0.09 I 0.75 I 0.19 I 0.30 I 0.17 】。 l I I エ＝戸 I I u:;::; ! , . 1 1

1 Mean .Value l叫（お）｜ム1851 1.46 J o.38 I o.57 1 o.44 J o.o9 J

;:-, ＂・淵 47, 176 l; I :>O I i 0.148! 1.93 I 0.38 I 0.29 I 0.17 I 0.08 I 0 ~X 631 190 Ur I<'• 1 0.1411 2.33 I 0.41 I 0.21 I 0.18 I 0.01 i '5 ~ 641 202 u I .-1() 1 i o. Iぬi2.31 0.15 I 0.26 : 0.21 I 0.07 :

i :¥kan Value 189.3：〔必） o.146! 2.19 I o.41 I 0.21 1 o.1s 1 o.07 I

2 ::-vm 1 -18 192 u, 11) 1 o.16s1 2.12 1 0.42 1 0.29 1 0.30 1 o.os 言戸E I 55i 186 l! { -18) I 0.1501 Z.49 I 0必 Io.2s I 0.21 I o.os Sミし 1一一一ーし｜ i I I I

j Mean Value 189.0 I (47) I 0.157j 2.30 I 0.42 I 0.27 I 0.28 ¥ 0.08 J

*・ .. Weight of Bilateral Epid ... ・Epididymides Prost .. ・・Prostate Organs Sem. Ves. ・Seminal Vesicle

一川石川一川一利一川

川町市一山一日

Table 14. Weights of Hypophysis, Thyroids and Suprarenals and Their Ratio to Body Weight in :¥Ialc Rats Administered Chorionepithelioma and Placenta Lyophi-lized I》owclcrfor 4 ¥¥'eeks.

Lil~＜＇ 1· : 1¥o. Doil、： ¥¥'eight 1 g-) I Ratio to B吋 W<'i旦ht(g/gxlO f I ¥¥'eight 一一一一’ ｜

Rats （ー lg:,_11»1山川 Th竺竺~J：竺竺！？？竺l~~~＿：：i~I 竺竺！？竺竺主＿1¥ ¥111 l 1001 86 I 0.0042 I 0.013 l 0.023 I 0.0048 I O.Dl5 I 0.026 ~ ~自 I 1011 11 I 0.0021 I 0.012 I 0.022 I 0.0035 I 0.0・15 I o.ozs 至宝：：： n i 1201 1s I 0.0035 I 0.013 I 0.022 I 0.0044 I 0.016 I o.ozs 包二ヨ XXll I 1301 68 I 0.0032 I 0.011 I O.Dl8 I o.o伽 6 I 0.016 I o.ozs 5さ xXlll I 133' 76 I 0.0036 I 0.011 I O.D18 I 0.0047 I 0.014 I 0.023

」~~~I~斗~~~1=0.020 l 0.0仰い石1玉E2 IXVIH f I I I ，－一一一一｜一一一一一｜一一一一一｜

門 I I J 02, 68 I 0.0025 I 0.010 I 0.021 I 0.0036 I 0.014 I 0.030 °' ::::- I 103 11 I o.oo四 I 0.011 I 0.021 I 0.0039 I 0.013 I o.ozg お2xx I 121: 74 I 0.0037 I 0.010 I O.Q18 I 0.0050 I 0.013 I 0.024 M 川！131' 74 I 0.0035 I 0.010 I 0似 I0.0041 I 0.013 I 0.032

I Mean Value 71.7 J 0.0031

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0.012 0.027 0.0053 O.Q15 0.034 0 012 0.023 0.0050 0.014 0.028 0.009 0.022 0.0052 0.013 0.032 0.009 0.023 0.0047 0.010 0.027

0.010 0.023 0.0050 0.013 0.030 : :¥Jc.an Yalu＜＇行 .7 I 0.003汁ホ Weightof Bilateral Organs

177 EXPERIMENTAL STUDY OF MALE PRECOCIOUS PUBERTY

Table 15. 明Teig-htsof Hypophysis, Thyroids and Suprarenals and Their Ratio to Body

Weight in Male Rats Administered Chorionepithelioma and Placenta Lyophi舗

lized Powder for 8 ・weeks.

Weiεht (g) I Ratio to Body Weig ht (g lg-x 100)

I Thy凶 5本＼Suprar匂 ls[Hypo向 s叶Th凶 ds[supraren山co cu

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p

nv

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I O.D18

0.021 0.019 O.D15 o.θ21 0.019

0.012 j 0.019

0.014 O.Dl 1 0.012 0.012 0.014

0.0033 0 0032 0 0037 0 0039 0.0039

0.042 0039 0030 0030 0033

0.031 0.021 0.022 0.021 0.025

0 0072 0 OC62 0 OC65 0 OC67 O.OC69

216 189 175 168 i

174 I

Mean Value山 l

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189 171 183 174 182

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Table 16. Weights of Hypo phys瓜 Thyro地 andSuprarenals and Their Ratio to Body

Weight in Male Rats Administered Chorionepithelioma and Cancer Lyophi-

lized Powder for 8 Weeks.

No. Body , Weight (g) I Ratio to Body Weight (g/gxlOO)

w（：ようht：函孟~I示yr

i 0.0072 I 0.031 i 0.042 I 0.0033 I j 0附 I 0.021 I 0.039 I 0.0032

0.0065 I 0.022 I 0.03＜〕 I 0.0037

Mean Value 193.3 ! 0.0066 I 0似 I o.037 : o.o側

三：11/lll I 47 I 176 I 0.0073 I O.D18 I 0.042 ー三目X I 63 I 1 so i o.oos1 ! o.ozs I o.033 5ζI I 64 I 202 I o.0063 ! 0.031 I 0.033 C .. H-'1 I I : ' I

I Mean Value 189.3 I 0.0064 I 0.024 I 0.036

空o.l¥11! I ~ 2iX I

8c§I I 一一一一i Mean Value 189.0 ¥ 0附｜*・・・Weight of Bilateral Organs

O.D18 0.020 0.017

0.023 0.017 0.016

0.014 0.011 0.012

0.010 0.013 O.D15

0.0041 0.0030 0.0031

216 189 175

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enter pubcrt；γ，i. e. approximately 30 cla~·s after birth, the ace白川町v sexual organs

of these rats reached a full.¥・ ripe只tntcsimilar to those of mature rats. Primogonγl

gave the most remarkable e百ecton the earl.）’ maturation of the accessory sexual

178 日本外科宝函；；／~28巻第 1 号

Table 17. Weights of Hypophysis, Tyroids and Suprarenals and Their Ratio to Body

Weight in Male Rats Administered Chorionepithelioma Lyophilized Powder

for 4 Weeks.

Littc1・ l'o. [ Body [ Weight (g) [ Ratio to Body Weight (g/g×100)

' Ro;t l ＂＇~~~ht IHy州 ysis長石弓布石1:151HypophysisI Thyr仙［supr…ls

去；而 i－~ 8~）1－~6-·· MO；－ー10.雨γ1－－－；正一I0.0051 ! 0.012 I O.QJ8 z国壬xxxI 1 <J3i s3 0.0036 I 0.0095 I 0.016 ! 0.0043 I 0.011 I 0.019 5号多l I 1911 82 0.0039 I 0.0080 I 0.017 I 0.0046 I 0.009 I 0.020 ・;EG1 I 19sl 68 0.0034 I 0.0095 I o.ois I 0.0050 I 0.013 I 0.023 t~ 'XX¥J I w1[ 18 ' o.o仰 Io.oogo I 0.016 1 o似 3 I o.仙 I 0.020

I Mean Value 77.4 ! 0.0 ¥ 0.00

¥'XI¥ 1邑6 74 : 0.0042 I o.oos5 ？三 ux 19例 72 : 0’0034 i 0.0080 」~ ;: ' 1971 80 I 0.0039 I 0.0100 包ζXXX!I 220! 82 I o刀03下 I 0心100 ζJ。 I I

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。目020

0.016 0.019 0.020 0.017

O.Ql 1 0.011 0.012 0.012

0.021 0.025 0.025 0.020

*・・Weight of Bilateral Organs

Table 18. Weights of Hyoophysis, Thyroids and Suprarenals and Their Ratio to Body

Weight in Male Rats Administered Chorionepithelioma Lyophilized Powder for 8 Weeks.

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organs. A clear sexual precocity was alrn produced with lyophilized powder of

h円laticlmole or chorionepithelioma. It is believed that actually these sexual

precocities were brought about 同・chorionic gonadotropin which is thought to be

日ecrctedfrom the chorionic tissue. 、Iti日 ¥I℃11 knovm that chorionic gonadotropin

(interstitial-cell-stimulating hormone) causes hyperplasia of LEYDIG cells, and allows

the LEYDIG cells to sec1じtca large amount of androgen, resulting in an earl)'

appearance of l he scconcla r.'・ sexual c harnc tcrist ics.

IV IHSCl1S只ION

1'1じ仁りじiuusl〕ubcl'ly accompanying a diencephalic tumor has b噌 11 COil己idel'€Cl b~


most investigators to take place through the stimulation or destruction by the

tumor of the higher sexual center in the hypothalamus (WEINBERGER-GRANT 1941),

though this them・.¥・ lacks a definite evidence. But according to FuKusHIMA in our

laboratory, three out of four cases of diencephalic tumor associated with the

precocious pubert，＼’＼＼.・ereteratomas and the chorioncpithelioma-like tissue was found within the tissue of these teratomas. In one of them, it seemed quite provable

from the increased gonadotropin value in the urine, that precocious puberty took place due to chorionic gonadotropin secreted from the tumor tissue.

LAIPPLY (1945) reported a case of the chorionepitheliomatous teratoma in the

mecliastinl,lm of a 13・〉’ear-oldboy showing sexual precocit~’ and h:-・perplasia of

LEYDIG cells. RHODEN (1944) found precocious sexual and somatic development in a 9・month-oldIm;: with a presacral tcratoma. Besides these, there are several reports

of precocious puberty due to tl!e tcratoma containing chorionepithcliomatous tissue

which originated in the testis 01・theovarium (SAcHII 1895, FAsow 1931). Therefore,

in the case of intracranial teratoma too, it ma:-・ be reasonable to assume that

precocious puberty may result from the chorionic gonadotropin secreted from chorionepithelioma-like tissue within the teratoma.

In one of the cases reported by FuKuSHIMA the hypophysis was almost comple-

tely destroyed, and therefore the gonadotropin, that had increased in the urine

could only be considered as having been originated from the chorionepithelioma-like

tissue in both the intracranial tumor and its metastases. The gonadotropin value

in the urine of this case was sufficient to cause early development of the secondary

sexual characteristics. Though in this case the body length was in normal range and no spermatogenesis was noticed in the testis, there were hyperplasia of LEYDIG

cells and early development of the distinct secondar:-・ sexual characteristics, i. e.

the changes corresponding to those in my experimental animals. Therefore, in this 伺 se,there is good reason to believe that precocious puberty associated with intra-

cranial teratoma would have been caused by chorionic gonadotropin from the tumor.

As the term macrogenitosomia praecox (PELLIZI) implies, many cases of preco-

cious puberty reported in the literature were not only accompanied by sexual

precocity but also by overgrowth of the body. Out of nineteens cases in the lite-rature of the pineal tumor accompanied by precocious puberty, in which the full

description of the somatic development (body length and body weight) was given,

eleven cases showed the distinct somatic overgrowth and the remaining eight cases

were at the upper limit of the normal growth. Besides, according to the literature,

in many cases of pineal tumor accompan~·ing precocious puberty, the testis was larger ancl spcrmatogenesis appeared earlier than normal.

In my experiment, though the early development of the accesson・ sexual organs

and of the secondar>・ sexual characteristics took place in almost the same way as

in the case of precocious pubert：－’ in humans, no precocious somatic grO＼＼ァth could

Le ob同rw~d，礼nd IJesides, the ad miniメtrationof lyophilized powder of chorionepithe-

lioma caused the decrease in the testicular weight ＼γith the tendenc.）・ toatrophy


of germinal eel l品 Though the accompaniment of precocious somatic growth is

common in cases of human precocious puberty due to pineal tumor, the somatic

precocit:i・ does not seem to be Eト＇sc11tialfor precocious pubert.＼’ bγfollowing reasons.

1) In the animal experiments reported in the literahirc on the e汀ectof chori-

onic gonaclotropin, early development of the sexual organs, especial＼；γof the acce・

日目。r>・ sexual organs w日目 recognized in all cases, but body clcvelopmcnt, though it

was seldom described satisfactorilγ，seems, as in myむxpcriments,to ha¥'C not been

excessi¥・e (BoETERS 1930, SMITH 1934). But in the case of clinical use of chorionic

gonadotropin for the treatment of patients with the retention of the testis, some・

what (THOMPSON 1938) or great (lcHIKAWA 1956) acceleration of bod>・ growth was

found simultaneously with cmヤ developmentof the sexual organs. l¥おreover,in ca刈只 ofhuman teratoma or chorionepithelioma of the ovarium, or of interstitial

cell tumor of the testis, somatic prccocit:i・ wa日 noticedin addition to abnormal

growth of the叩 xualorgans, especiall>・ of their accessories (HARRIS 1917, CosTIN

1948, STAUBNITZ 1953). Thus itぉccmsthat there maγbe some cli町erencesbetween

men and animals in the accelcr<ltion of ])Ocl~’ development during the peri吋 of

puberty (whether it is naturally or artificially induced).

2) The second reason is that chorionepithelioma has the ability to secrete various kinds of hormone other than chor・ionic gonadotropin, and the proportion of

those hormons di仔ersin each chorionepithelioma. In all cases of precocious puberty,

earlγappearance of the seconclar＞’ sexual characteristics is an indispensable pheno・

menon but early body development is not al ways present, and, if it is, varies in

degree case b>・ case. Therefm・e,a l〕O出 ibilitγcanalso be suppm:ed that early deve・

lopment of the bocl:i・ dependson the character of the hormone secreted by such tumors.

Next is the problem pertaining to the testis. The increase in the weight of

testis and the appearance of spermatozoa are not so charade; i日ticof p1悦 ocious

pul陀rt>・as the、earl＞’ appearanceor the seconclar≫ 日exualcharacteristic日．

人ccordingtけ theresults of Ill.¥・ experiment, after the administration of Primo・

gon.d for 4 weeks, spermatozoa appeared which were not observed in the control

group, whereas after 8-wcek administration of Primogonyl spermatozoa were found

in both groups in a nearly epual amount. Of the groups to which l;;ophilized pow・

der of chorionepithelioma was administered, atroドh.＼’ ofgermimd cells was noticed in the 4-weck group, whereas in the 8・week group germinal cells we1℃ found to

have returned to normal. But when the amount of powder was decreased, it was difficult for germinal cells to come to atroph)'. Thus it can be assumed that

histological cha 1igc of the叩 mi1iiferoustubules clepencls upon the amount of powder

and the length of periocl of aclrninistrntion. Therefore, also in this regard, I cannot believe that there is an essential difference between human precocious puberty

accor:i.panied IJ>. pineal tumor and that of my experimental animals. However, it に仁emsimpo出 iiJleto explain all cases of cerebral t；，’pc of precocious

pubert.¥' from the standpoint of the on tけg・仁11ic theory, IJccawじ th仁reare ca~ cs of precocious pul1eri;.・ cau吋 clli.＼ヤ広lioma,cncephaliti日 andoth℃r non-neoplastic lesions.

Yet, the majority of cetscs (appro~imatel~’ 3/4) of precocious puLerly accom・


panied by pineal tumor are the cases of teratoma (KRABBE1923, HoRAx and BAILEY

1925, KITAY 1954), and also in Japan, eight out of eleven cases were reported to

be due to teratoma. Besides, according to RussELL (1944), pinealoma is all atypical

teratoma. Moreover, an elaborate histological examination of teratomas revealed,

at times, that they contained chorioncpitheliomatous tissue in a part and such

tumors, if the~’ developed prior to puberty, ga¥'e rise to precocious puberty (WIRTH

1929, D. S. RussELL 1944，も"ff.0. RussELL 1945, ZoNDECK 1953). Also, from the fact that the majority of cases of cerebral type of precocious

puberty are accompanied by pineal tumor and that almost all such patients are

males, the development of precocious puberty seems to be easier to understand from

the standpoint of the ontogenic theory than from that of the hypothalamic theory.

Besides, it has been known that an overwhelming number of cases of extragenital

teratoma, especially those of intracranial teratoma have been observed in males. In

considering these e¥・idences together with the results of my experiments, I believe

the old ontogenic theory should be taken into consideration once again, even though

it seems unlikely that all cerebral types of precocious puberty can be explained

according to this theory・

su:¥DIARY

1) By the administration of a large amount of chorionic gonadotropin (Primo-

gonyl and lyophilized powder of chorionepithelioma) to immature male rats, dis-

tinct sexual precocity took place, though accompaniment of early somatic develop-

ment could not be noticed.

2) It is possible that the precocious puberty occurring in cases of diencephalic

tumor may be caused h’ the gonadotropin secreted from the tumor.

Thanks are expressed to Dr・.NAO:KC KA日EYAlrAfor his kind suggestion during this study.

REFERENCES I) Araki, C. and Handa. H. : On the Function of the Pineal Body, Xaibumpi no Tsudoi, 8. 226.

1956. 2) Araki, C. and Fukushima, K. : Preco-cious Puberty and the Tumor of the Diencepha-lon, Saishin Igaku, 12. 2518, 1957. 3) Askanazy, N. : Teratom und Chorionepithe-li01n d. Zirbel, Verhandl. d. Deutsch. Path. Gese-llsch., 10. 58, 1906. 4) Boeters, H.: Prolanver-suche am Jungen M忌nnlichenRatten, Deutsch・ l¥Ied. Wsch., 56. 1382, 1930. 5) Bauer, H. G. : Endoci・ine arnl Other Clincal Manif巴stationof Hypothalamic Disease, A Survey of 60 Cases, with Autopsies, J. Clin. Endocrinol., 14. 13, 195-1.

6) Costin, M. E. and Kennedy, R.: Ovarian Tu-mors in Infants and Children, Am. J. Dis. Child. 76. 127, 1958. 7) Engel, E. T. : The Response of the '.¥Iale G0nital System to Treatment with Urine from Pregnant Women and from Men, Anat. Rec. 43. 187, 1927. 8) Frankle-Hochwart: Uber Diagnosed. Zirbeldriisenturnoren,Deutsch.

Ztschr. f. Nervenheilkunde, 37. 455, 1909.

9) Fukushima, K. : Tumor the Diencephalon and Precocious Puberty, Arch. f. Jap. Chirur. 27. 553, 1958. 10) Harris, R.H.: Carcinomatous Ovarian Tcratoma with Premature Puberty and Precocious Somatic Development, Surg. Gynec. & Obst. 24. 609, 1917. 11) Horrax, G. and Bailey, P.: Tumor of the Pineal Body, Arch. :'.'/enrol. & Psych., 13: 423, 19ゴ5. 12) Horrax, G. and Bailey, P.: Pineal Patholog・y; Further Studies, Arch. Neurol. & Psych., 19. 394, 1928.

13) Handa, H. : Experimental Studies on the Function of the Pineal Region Controlling the Somatosexual Development in Male Chickens, Acta schlae Med. Uniγ. in Kyoto, Japonica, 31. 143, 1953. 14) Ishisaki, C.: A Case of Pineal Tumor with Macrogenitosomia Praecox, Osaka lgakkai Zasshi, 29. 1147, 1930. 15) Ichikawa, T.: Ph）’sex Leo and Antex Leo, Chiryo, 38. 55,

1956. 16) Krabbe, K. H. : The Pineal Gland Especially in Relation to the Problem on Its

182 日本外科宝函第28巻第l号

Supposed Significance in Sexual Deγelopment, Endocrinol., 7. 379, 1923. 17) Kitay, J. I.: Pine-

al Lesion an<l Precocious Puberty : A Review,

J. Clin. Endoclinol., 14. 622, !954.

18) Kageyama, N. : Experimetal Study on the

Interrelation betwe0n the Pineal Body and the

Hypophysis, with Particular Reference to the Somatosexual Development, Arch. f. Jap. Chi-

rur., 24. 470, 1955. 19) Laipply, T. C. and Shipley, R. A. : Extrag・enitale Chorionpitheli-

orna in the Male, Am. J. Path., 21. 921, 1945.

20) Lange-Cosack, H. : Verschiedene Gruppe d. Hypothalmischen Pubertas Praecox. IL Se-

xuelle Fruhreif bei Verschiedenen Hypothal-amischen (mit Ausnahme d. Hypothalamischen

Missbildung un<l bei Zirbcltumorcn), Deutsch.

Ztschr. f Nervenheilkunde, 168 237, 1952.

21) Nagayo, M. : Abnormal Development of

Sexual Organs in Children (in the Case of

Pineal Tumor〕， ShonikaZasshi, 217. 159, 1918.

22) Nagayo, M.: Pathology of the Pineal Body

Shinkeigaku Zasshi, 18: 1, 1918. 23) Nagano,

T. : Several Cas~s of Brain Tumors, Shonika Zasshi, 354: 1956, 1929. 24) Russell, D. S.: The

Pinealoma, Its Relationship to Teratoma, J.

Path. & Bact., 56. 145, 1944. 25) Russell, W.,

0., Sachs, E. and Stowell, R.E. : Primary Intra-cranial Chorionepithelioma with Metastases to the Lung, Am. J. Pth., 21. 787, 1945.

26) Rhoden, A. E, : Precocious Sexual and So-

matic D2velopment in a Male Infant with a Presacral Teratoma Containing An<lrogenpro-

ducing Tissue : with Discussion of Mechanism

of Precoeity Caused by Teratoma. J. Clin. En-tlocrinol., 4. 185, 1944. 27) Smith, P. E, and

Leonard, S. L,: Responses of the Reproductive System of Hypophysectomized and Normal

Rats to Injection of Pregnancyurine Extracts,

Anat. Rec., 58. 145, 193-1. 28) Staubnitz, W. J.:

Precocius Puberty in a Case of Bilateral Inter・

stitial Cell Tumor of the Testes, J. Urol., 69.

562, 1953. 29) Suzuki, Y. : On the Sexual Ma-turation Process in the Rat, Naibumpi no Tsu-

doi, 8. 101, 1956. 30) Thompson, W. 0. & Heck-

el, N. J. : Precocious Sexual Development fr-

om an Anterior pituitary Like principle, J. A.

M. A., 110. 18日， 1938. 31) Takeya, H.: A

Case of pineal Tumor with could be Diagnosed

Clinically, and was Verified by Autopsy, Sh-

inkeigaku Zasshi, 12. 463, 1913. 32) Tsuchida,

U. : A Case of Pineal Tumor, Shinkeigaku Za-

sshi, 17. 62, 1918. 33) Tanaka, T. : A Case of

Pineal Tumor, Rhinshoigaku, 8. 1012, 1918.

34）羽Teinberger,L. M. & Grant, F. C.: Preco・

cious Puberty and Tumor of the Hypothalam-

us. Report of a Case and Review of the Liter-ature, with a Pathophysiologic Explanation of the Precocious Sexual Syndrom, Arch. Int.

Med, 67: 762, 1941. 35) Walton, K.: Teratoma

of the Pineal Region and Their Relationship

to pinealomas, J. Path. & Bact., 61. 11, 1949.

36) Wirkins, L. : The Diagnosis and Treat-ment of Endocrinologic Dis2ase in Children and Adolescence, Springfield, III, 1950.

37) Zondek, B. & Sulman, F. : The Mechanism

of Action and Metabolism, Vitamin and Hor-mone, 5. 297, 1945. 38) Zondek, H., Kaatz, A.

and Un広er,H. : Precocious Puberuy and Chori-

onepithelioma of the Pineal Gland with Report of a Case, J. Endocrinol. IO. 12, 1953.


和文抄録

繊毛性 Gonadotropinによる雄性 Pubertaspraecox

の実験的研究

京都大学医学部外科学教室第I講座（指導：荒木千里教授）

吉川昭治

松果体腫疹に伴うPubertasPraecoxの発生原因に

関して Askanazy(1906）はp 腫療組織に合れる繊毛

上皮腫様組織よりの性腺刺戟ホルモン様物質分泌を考

えて Onto邑：eneTheorieを提唱した．併しその後この

説に対する多くの反論が現れ現在では殆ど省みられな

くなった．

然るに我々の教室の福島は京大第I外科に於ける

Pubertas praecoxを併発した脳虚疹4例一一松果休

腫蕩3例（内奇形腫2例）下垂体部奇形腫 1例ーーを

詳細に組織学的検索を行いp 奇形腫3例中2例に繊毛

上皮腫様組織， l例には Cytotrophoblastoma様組

織を認めた．更に他の 1例では大部分Pinealoma組織

であるのに一部に腺様構造を認め，これも奇形腫であ

る可能性があった．即ち我々の教室例4例中3例は繊

毛性 Gonadotropinを出し得る組織を有して居り他の

l例にも同様の事が考えられた．中でも下垂体奇形態

の 1例では下垂体は殆ど完全に破壊きれ前葉細胞は全

く認められなかったのに尿中 Gonadotropin値は著明

に地加して居た．

従ってこの Gonadotropin値の増加は渥疹組織に合

れる繊毛上皮援によることは明らかであり，この症例

に於ける Pubertaspraecoxは繊毛性 Gonadotropin

によって発現したと考えられ，他の 2例にも同様の事

が想像された．これらの事実より OntogeneTheorie

を再検討する必要がみると考えて繊毛性Gonadotrop-

inとPubertaspraecox との関係について動物実験

を行った．

実験動物は同腹の幼若雄ラッテを使用し繊毛性Go-

nadotropinとしては Primogonyl (Schering Co.)

及び2例の繊毛上皮麗組織よりつくった凍結乾燥粉末

を生後5日目より前者は 1日30I. U.毎日皮下注射，後

者は 1日JOmg週3回皮下注射を行い＇1週毎に｛本重

を測定し，投与4週間（生後33日）投与8週間（生後

61日〉で屠殺，性穏重量及び内分泌臓器の組織学的検

査を行った．

実験結果は Primogonyl及び繊毛上皮麗凍結乾燥

粉末によって身体早期発育（身長p 体重の増加）は来

さなかったが，第二次性微の早期発現，副性器の著明

な早期発育を認めた．即ち雄ラッテが思春期に達する

と考えられる生後30日前後で副性器は成熟ラッテに相

当する発育を来した．皐丸では重量は却って減少した

が Leydig細胞の著明な増殖あり， Primogonyl投

与では精子形成の早期発現を認めた．

以上の結果より，間脳部腫蕩による Pubertas

praecoxは間脳部障害によるもの以外に，屋疹組織

より分泌される Gonadotropinによる可能性が相当濃

厚なものと考える．

Documents

Title EXPERIMENTAL STUDY OF MALE PRECOCIOUS PUBERTY …repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/206748/1/ngh028001_158.pdf · Boy, 9 >・ca rs 4 months old, clearly manifestating