Testosterone, prostate gland and hormone action

Vol. 32, No. 3, 1968

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

TESTOSTERONE,

PROSTATE

Etienne-Emile

BAULIEU*,

’ Lab Hormones,

Received

94 - Bicltre, Laboratory,

changes

there

to DNA

and Atchl.ey, Without

with

here

ROBELO Research

tissue,

molecules

Oestradiol the target 1966

; Ofner,

1965).

Recent

1967)

ind.icate

and the most

(Resko,

Feder

its transformation

rat uterus

and Jacobson,

prostatic

tissue

Chamberlain

into

natural 1968))

its

out

particular

that

hor-

the “hormone”

interacting is probably

1962).

In contrast,

(Harding

with

the

1966 Mercier

known

androgen

reduced

derivative

in

1962

are

; Pearl-

; Farnsworth, and Lasnitzki,

secretory

circulating

may be active

unchanged androgens

and Samuels,

Robel, the well

testosterone, potent

ma-

be pointed

each

and Jagarinec,

(Baulieu,

and Goy,

likely

1966).

experiments that

significance.

it should

the possibility

of

b) and it was

the most

considering messenger

on prepuberal

(Jensen

by rat

primarily,

chemical

(Baulieu,

organ

metabolized

are

the

Binding and Goldberg

(1966a,

histones

or late

at present,

(1964)

physiological

and especially

acting

and Lu,

of general

bind

early

efficiently.

by Sluyser,

without

be the actual

involves define,

interact

and/or

hormones

to generalize

and target

testes

, and Paul

action

by Ts’o

were

if DNA

to which

may not always tissular

tested

the results

d.iscussing

it is difficult

man,

ACTION

one cannot

hormones

and to histones

that

cromolecules

hormone

events,

which

has been

(1966)

assumed

that

biosynthetic

target

hormones

mone

LASNITZKI+

HORMONE

France and + Strangeways Cambridge, England.

is evidence

in nuclear

intracellular

that

Use

AND

July 10, 1968

Although

often

GLAND

product

of

in the blood

at least

partially

androstanolone

through (178 -

hydroxy-SK-androstane-s-one). Exp.lants

of ventral

kept

24 hours

were

for

in Parker’s terone, centration

medium either

prostate in an organ

culture

of 5-6 weeks system

199 with

5 x 10-7

maintains

glands

(Lasnitzki,

10 % calf serum to which , was added. M or 5 x 10 -5,

the structural

differentiation

575

old hooded

rats 196!j),

tritiated testosThe latter con-

of the prostatic

tissue,

Vol. 32, No. 3, 1968

in particular plasia

epithelial

may also

sion sis

8lOCHEMlCAL

cell

showed

pounds

a nuclear

were

chemical Ninety

extracted

fraction.

cent

of tissular

Testosterone where

2 relatively

being

androstanolone.

tion

came to our

androstanolone

(Bruchovsky

OF

was

found

1968) 1968)

TESTOSTERONE

in the cyto; in the

amounts, new

and the selective

one

informa-

of testosterone

by prostatic

AND

radio-

steroids.

nor

studies,

the metabolism

and Liao,

rigorous

observed

in equal

of these

and Wilson,

(Anderson

EFFECTS

were

corn -

in the cytoplasmic

in the nucleus

the course indicating

Radioactive

present

compound

steroids

During attention,

of the metabolite

neither

fractiona-

and quantitating

was

polar

nonpolar

is regresan analy-

cell

and the most

identifying

radioactivity

unidentified

hy-per-

there

after

fraction.

solvents

for

was found

a still

nuclei

in the tissue

organic used

epithelial

In the two experiments,

present

with was

; some

concentration,

and a “cytoplasmic”

methodology per

plasm

compounds

RESEARCH COMMUNICATIONS

and secretion

At the lower

and no secretion.

of radioactive

tion

height

be observed.

of the epithelium

AND BIOPHYSKAL

to uptake

nuclei.

ANDROSTANOLONE

ON RATPROSTATEINORGANCULTURE hxgt$yi;

Height

Secretion

Hyperplasia

the medium TESTOSTERONE 1;:;

+ +

+ +

35

f

ANDROSTANOLONE 1;:;

f f

35

In a second drostanolone explants

the effects

set of experiments,

on rat were

+ -+ it

prostatic

incubated

serum

in the presence

steroid.

Histological

for

tissue

6 days

of testosterone

and an-

grown

were compared. The --in vitro in Parker’s medium 199 with 5 % horse

of 3.5

x 10s5,

analysis

showed

1.8 x lo-5 that

576

at each

and 3.5

x 10-6

concentration,

of either andros-

Vol. 32, No. 3, 1968

tanolone height

was and

BIOCHEMICAL

much

weaker

secretory

epithelial

at a dose

degree

of hyperplasia

centrations

These

results

nuclear

M induced

suggest

elements

the testosterone hypothesis

terone

x 10-6

(table

that

action

that

nuclei,

division after

at 3.5

and induced

testosterone

x 10-S

approximately x 10-S

to extensive

studies

M

up

; andros-

the same

M,

and higher

con-

hyperplasia

of interaction

necessarily

on the prostate

metabolites (Baulieu,

rise

epithelial

of the

I>.

is especially could

Lasnitzki

be involved and Robel,

of testosterone

to further

gland.

Data

, one of the testosterone

androstanolone

in prostate other

maintaining

cell

at 3.5

gave

do not lead

action

for

no hyperplasia

hyperplasia

as testosterone

epithelium

and found

was

slight

of androstanolone

prostatic

whereas

of 3.5

testosterone

but it stimulated

There

M and some

tanolone

with

activity

hyperplasia.

to 1.8 x 10-S

than

AND BIOPHYSICAL RESEARCH COMMUNICATIONS

concerned in other

insight

support

into

the working

metabolites with aspects

cell

made

division, of testos-

1968).

This work has been partially supported by 1’1. N . S . E . R . M . , la Delegation GCnerale Scientifique et Technique, the Ford Foundation, the Sir Halley Stewart Trust and the British Empire Cancer Campaign for Research. REFERENCES submitted for publication (1968). Anderson, K.M. and Liao, S., Nature, Proc. of the 2nd Inter. Congr. on Hormonal Steroids, Baulieu, E.E., p. 37 (Excerpta Medica Foundation) (1966). Lasnitzki, I. and Robel, P. , Nature, submitted for Baulieu, E.E., publication (1968). C. and Lasnitzki, I., Baulieu, E.E., Robel, P., Mercier-Bodard, Abstract, Third Meeting of the International Study Group of Steroid Hormone, Rome, (C. Cassano ed., In press) (1967). Bruchovsky, N. and Wilson, I.D., J. Biol. Chem., 243, 2012 (1968). Farnsworth, W.E., Steroids, 5, 519 (1965). Goldberg, M.L. and Atchley, W.A., Proc. Natl. Acad. Sci., Wash., 55, 989 (1966). HarGg, B. W. and Samuels, L.T., Endocrinology, 70, 109 (1962). Jensen, E.V. and Jacobson, H.I., Recent Progress inHormone Research, G. Pincus ed. , 2, 387, Academic Press (1962). Lasnitzki, I., J. Nat. Cant. Inst., 35, 339 and 1001 (1965). Ofner, P., Chamberlain, J. and Jaganec, N., Biochem. J., 99, 610, (19661. ‘,~z;ma;~W .H., J. Biol. Chem. , 22, 411 (1966). Feder, H .H. and Goy, R. W. , J. Endocrin. , 40, 485 (1)968): ’ Sluyser, M., Biochem. Biophys . Res . Comm. , 22, 336 (1966a). Sluyser, M., J. Mol. Biol., 22, 411 (1966b). Ts’o, P.O.P. and Lu, P., Pror. Natl. Acad. Sci., Wash., 51, 17, (1962).

577