0022-1

554/82IOO67O5SO2.5

The Journal of Histochemistry and Cytochemistry Copyright 1982 by The Histochemical Society,

Vol. Inc.

30,

No.

pp.

6#{149} -#{244}81 . 1982

Printed in U.S.A.

II
Nuclear the Rat:
Effects
J.M. JACOBI,
of Medicine. for publication

Diameter

in the

Anterior

Pituitary

Gland

of

of Estrogen,
H.M. LLOYD,

Bromocriptine, and
1981 and

and
MEARES
Sciences form Building. December Royal 22,

HaloperidoP

J.D.
Clinical in revised

Department Received
126)

Unizersity February

of Queensland. 9,

Brisbane 1981
;

Hospital.

Brisbane

4029. 3 1, 1981

Australia (OA 81-

accepted

December

Nuclear diameter, DNA synthesis, and mitotic index in the pituitary cells of male rats and serum prolactin were measured after a period of 8 days of treatment with a dopamine agonist and an antagonist given with and without estrogen. In the absence of estrogen, the dopamine agonist, bromocriptine, diminished the mean nuclear diameter of the pituitary cells and lowered pituitary DNA synthesis, and the dopamine-blocking agent halopenidol had no effect. Estrogen increased the mean nuclear diameter, pituitary mitotic index, and DNA synthesis. Bromocriptine prevented the estrogen-induced increase in mean

nuclear diameter and pituitary DNA synthesis and mitotic index were lowered. Haloperidol augmented the estrogeninduced increase in mean nuclear diameter, pituitary D NA synthesis, and mitotic index. Positive correlations were obtained between mean nuclear diameter and DNA synthesis and serum prolactin. It was concluded that nuclear diameter was influenced by both DNA synthesis and secretory activity in pituitary cells.
KEY WORDS.

Pituitary; Haloperidol.

Nuclear

diameter;

DNA

synthesis;

Bromocriprine;

Introduction
Early trophy with studies was growth of endocrine with More cells tissue revealed that secretory nuclear found tumor correlation cell to size nuclear activity (diameter) hyperand of associated (4). adenoma to be correlated adenomas diameter of increased

to be similar of prolactin
tine appeared

to that of cells obtained

to be reduced

untreated from
(9).

rats

cells ( 1 ). The treated with secretion and

anterior

nuclear size bromocnipis a dopamine

Bromocriptine

agonist the effects estrogen) previously prolactin rat

known (13,18). on nuclear

to inhibit
mitotic

prolactin
activity in

to suppress
pituitary of

recently, was with no

estrogen-induced

the

parathyroid

be related
( 16). was found and

to ploidity
In a study between parathyroid

There

is no

information of dopamine

with

regard

to the (except

(3)
of mean

and

weight

diameter

antagonists

parathyroid nuclear

tumor

nuclei

DNA

synthesis,
nuclei gland, little

although
measured information

76%
6 j.tm

of tritiated
(17). In nuclear about

thymidine-labeled
the case of the pi-

that increase shown that secretion and

DNA synthesis

the secretion of prolactin. We have haloperidol given by itself increases stimulates both prolactin secretion and
when given with estrogen (15). The

(S

phase)

pituitary

tuitary

size

is available.

purpose of these
nuclear

of the present agents

size is specifically

investigation diameter
related

was and
to

to examine to determine
DNA synthesis

the effects whether

on the

Changes
tuitary cells

in shape
taken

and
from

chromophobe
pituitary synthesis tigate their gland and

cells
in secretion relationship

density of nuclei were observed in picastrated female rats (8) and in pituitary of rats given cortisol (12). Studies of the
various have with agents provided nuclear influence opportunities diameter. For both to DNA inves-

on nuclear

one

hand

or to secretory

activity

on

the

other.

which

example,

Materials
rat

and

Methods
dipropionate ofethyl oleate
(Sandoz, weight of 6 parts activity saline. BasIc) potassium of

estrogen
lactin pituitary (13).

affects
cells

pituitary
cell with treated

cell

division

and
was nuclear

secretion
observed size was

of proin stated

Although

hypertrophy estradiol,

Materials. Diethylstilbestrol Baker) was given in a vehicle

mg per ml. Bromocriptine an alcohol, equal and (specific Centre, containing absolute

(DESD) (May and at a concentration of 10

was dissolved (Searle, lactic was acid purchased in a vehicle tartrate, in 1 part Australia) saline. from hydrogen

Haloperidol 0. 1 / Ci/mmol)

was
Supported by a grant from The National Research Council of Australia and the Queensland Health and Medical Cancer Fund. the

dissolved
Radiochemical

in a vehicle

consisting
15-30 Amersham.

[HJ-Thymidine

677

678

JACOBI,

LLOYD,

MEARES

Animals.
in a light-

Male
and and a daily

Sprague-Dawley
a pellet injection of8 by glands days. were diet ad of

rats,
libitum. bromocniptine g body rats neck

aged
Groups

3 months,
and of seven (0.3 mg/tOO or the on the sagittally. during

were
maintained rats vehicle

kept
each at

Fast Red,
sections apparently of nuclear pituitary

as described
and the small diameter glands with larger nuclei may

above.
the in a cut result large

It should
nuclei, from the the section.

be noted
greater Some use will

that
be

the thinner
the sections number in distribution

the
of

temperature-controlled

environment

on were

tap

water given

skewness of 4 m

g body morning Blood

in those

weight) 04:00 of the anesthesia.

was

or halopenidol hr for a period eighth day Pituitary

(0. 1 5 mg/l00 All the of the section

weight) were arteries killed halved

nuclei.

chloroform

removed

and

Cytophotometry stained slides were

densitometer diameter field, and with About area

measurements examined under

a 1.3 100 NA x 100 and nuclei

of nuclear area. The Feulgena Vickers M86 scanning microapochromatic spot each of the of rats of section nucleus given objective, 0.48 were vehicle, as described glands cells were .tm were a 40 and noted. or DESD above, fixed were examined. m 0.95

kept

for radioimmunoassay. of prolactin.

using NIAMDD rat described to methods

illuminated,

a flying from

Radioimmunoassay
tin was carried out according preparation

Radioimmunoassay
prolactin RP-l previously (10).

of prolacas reference

.tm

diameter.

Absorbance

measurements Further groups or killed. and

Mitotic DNA
gland the with and

index.
without

Pituitary
synthesis as described for 3 hr in was

DNA
estimated previously medium

synthesis
(in (10). 199

and radioautography.
vitro) The containing in one-half half pituitary 1 pCi/mI of each gland

Pituitary
pituitary was

bromocriptine the rats were

haloperidol, Whole pituitary and the

were given
90 mm and stained

colchicine
with (13).

(0. 1 mg per 100 g body weight)

eosin

intraperitoneally
in mitosis

incubated

before

[3H}-thymidine;

hematoxylin

DNA was extracted by Burtons method (5) and the radioactivity the DNA was counted. The other half pituitary gland, incubated for the estimation of DNA synthesis, was fixed in 10% formalin
saline and and processed embedded through in paraffin. xylol, Sections alcohol, of4 p.m and thickness 70 and 50% were absolute alcohol

in as in
cut

counted

Statistics. Significance of difference was calculated by Students test. Correlation coefficients (r) were calculated for log values of the

variables.

to water. The (Ilford) heated

for acid counted 5 days, the

slides were coated with photographic to 45#{176}C a water bath. After exposure in
sections alcohol. were The developed and stained with cells total to

emulsion K2B in total darkness

0. 1 % Nuclear

Results
The results for all variables of rats given bromocriptine, without estrogen are shown of histograms
p.m) estimated

Fast Red in 5% aluminium

in absolute for each

sulfate,
number 1000 from

followed
of labeled cells. 80,000 The

by a wash
was

in 0. 1% picric
counted of and cells number

expressed

as label

index
group

per
ranged

(mean SEM) for the six groups halopenidol, or vehicle with or in Table I . Figure 1 is composed of nuclear diameters
sections.
=

160,000.

of the
from

range

(4.5 26-7.320
The was was smallest in than observed lower

Nuclear diameter. Sections of pituitary tissue (4 tm thick), prepared as described above, were hydrated, rinsed in cold N HC1, and hydrolyzed in 5 N HCI for 2 hr at 20#{176}C. After one rinse in cold N HCI and several rinses in distilled water, the slides were stained with
Schifrs 0.5% being reagent potassium dehydrated (de Tomasi and method) in 5% in for N 1 hr, HCI, rinsed then (19). in a solution in water, Mean before Nuclear of metabisulfite mounted

Feulgen-stained

mean that
groups

nuclear ofthe (

diameter

(MND
rats and

4.526
mean

,tam) value

bromocniptine-treated

the

controlgroup <0.01-0.001).

(p <0.001) Estrogen

and ofall increased

the other treated MND compared (Table 1). MND was that of the given in-

Polymount

Diameter (MND) the aid of a Wild

proximately estimated on 1000 the

was estimated on the Feulgen-stained sections with ocular graticule, as described previously (16). Apnuclei were counted in each nuclei section. stained MND with was also Nuclear (5H]-thymidine-labeled

to the When further group with

vehicle-treated halopenidol increased given estrogen

control group (p <0.001) was given with estrogen, the and was larger (p <0.02) than alone (p (Figure <0.01)

estrogen lowered

1). Bromocriptine the estrogen-induced

Table

1 . Mean rats per group)

values

SEM for variables

measured
MND-labelled nuclei
(sam)

in rats given
Mitotic index
(mitoses/sq

8 days of treatment
Label
index mm) (per

with

the agents
DNA

shown
Serum
prolactin (ng/ml)

(five to seven
Area
nucleus (arbitrary units)

Pituitary wt
Group (mg)

MND
(aim)

1000

cells)

synthesis (dpm/tg DNA)

Vehicle

8.8
1.0

5.609
0.200

5.382
0-2

0.33
0.03

178
18

40 4

11.74 0.65

Bromocriptine
Haloperidol

8.2
0.2 9.1 0.3

4.526
0.034 5.346 0.188 6.616 0.216 5.247 0.243

5.684
b

0.25
0.02
b

65
7

6
1

10.38
1.12

5.284 5.975 5.468

0.50
0.13 1.51 0.22 0.40 0.04

174
20 582 65 256 31

72
4 151 10 53 6 290 58

13.58
1.41 13.11 0.42 12.60 0.58 14.58 0.80

DESD
DESD

vehicle bromocniptine

12.0 0.3 9.8 0.3

9.88 1.22 6.70 1.10

DESD

halopenidol

16.6
0.4

7.320
0.132

6.380

15.72
1.30 labeled. normal.

2.60
0.44

997
137

MND

was

measured

hNot

measured.

Test

in approximately too insensitive

30 to 60 nuclei radioautographically to demonstrate minor changes from

NUCLEAR

DIAMETER

IN

THE

RAT

PITUITARY

GLAND

679

50

Table

2.

diameter treatment

Number expressed group

of nudei measuring 3 to 1 0 pm in as % of the total nuclei counted for each

Diame ten in zm 5 6
7

Group

10

0 50

Bromocriptine

5
1 2

44
14 17

40
45 26

9
32 30

1
7 16

Halopenidol Vehicle

3
3

0
0

0
0

Estrogen Estrogen + bromocniptine Estrogen +

0 0

0
4

5
19

11
43

28
25

35
5 34

20
3 30

4
0 11

0
0 2

18

5g
Q

halopenidol
C

group of rats. MND of tritiated thymidine-labeled nuclei of the radioautographs measured from 5.284 .tm (in the group given halopenidol) to 6.380 .am (in the group given estrogen
U,

and similar groups showed

haloperidol) to given significant those

(Table of

1 unlabeled

).

The

MNDs
nuclei, and estrogen

of labeled
and only with

nuclei
those of halopenidol

were
the

5#{176}d

bromocniptine differences not

(P <0.001)
significant) was

(Figure
found

2). A corbetween the

relation MND the

5-

(r

+0.78,p

of labeled that given

nuclei became

and

the

MND was

of unlabeled

nuclei

in

six groups Areas

significant measured
(arbitrary

(r

+0.97,

p <0.01)

0 50

if the group

bromocniptine nuclei
46.24 to

omitted. by the
units). The

of individual
from 2.82

densitometer
lowest mean

ci ci

ranged

value ( 10. 38) was found for nuclei of bromocniptine-treated rats and the highest (14.58) for nuclei of rats given estrogen

r-4T
d

and halopenidol (Table 1). Only halopenidol showed a significant trol. The groups ocniptine
halopenidol

the group given estrogen increase ( <0.05 ) above and mitotic not given synthesis
presence of

plus consix and

pitui-

5g

results

of DNA in Table

synthesis DNA
In the

index estrogen,

for the

are shown lowered

had no

1 . In rats

brom-

pituitary
effect.

(p
index

<0.001) were
rise in

estrogen,

0 ,,um 2 34

rTI1L
5678910

tary tary the

(t
=

DNA DNA difference

synthesis, synthesis

mitotic
the

index, and

and

label

raised.
pitui-

Bromocriptine

decreased

estrogen-induced

(P <0.001)

label

index reach the

(p

<0.02), significance estrogen-in-

but

Figure 1 . Histograms representing the distribution of nuclear diameter (gm) in approximately 1000 pituitary cells from groups of rats given a dopamine agonist and an antagonist with and without estrogen for 8 days as indicated below. (Values noted are mean and SEM, respectively.) (a) Bromocriptine (0.3 mg/tOO g body weight) MND = 4.526 0.034; (b) DESD ( 10 mg) + bromocniptine MND = 5.247 0.243; (c) haloperidol (0. 15 mg/100 g body weight). MND = 5.346 0.188; (d) vehicle MND = 5.609 0.200; (e) DESD MND = 6.616 0.216; (1) DESD + haloperidol MND = 7.320 0.132. The column showing nuclei measuring 7 jim has been shaded to demonstrate the increase in MND.

1.94).
rise

in mitotic Haloperidol in pituitary

index did further DNA synthesis

not quite increased

duced prolactin creased

(p

<0.02), (see ( Table <0.00

mitotic

index

(P <0.01),

and label was lowered by haloperidol

decreased

index (P <0.05) by bromocniptine

1). Serum 1 ) and in(P <0.001).

inpro-

(p <0.001)
(P estrogen-induced <0.001)

and

estrogen
and increase

Bromocriptine

halopenidol in serum

creased
lactin.

(p

<0.05

) the

ables

Positive from

correlations each group,

were obtained between as shown in Table 3.

means

of van-

crease MND
of data the on

in MND. was
group the

In different

the

group from
with

given that
measuring

haloperidol of controls
3nuclei 1 0 .tm counted,

alone, nor
Table

the that

not
given number as

from
in diameter, for

Discussion
Without which cell However, specific types staining the
that

estrogen of cent nuclei of

bromocniptine.

2 gives

it was
estrogen

not

possible
is taken up

to determine diameter occurred.

types in all cell

in

changes

in nuclear

expressed

a per

the

total

each

it

is known

680

JACOBI,

LLOYD,

MEARES

8
7

of 7, 8, and ocniptine 8, and estrogen smaller

9 jam

nuclei

to 77%.

On

the

other

hand,

bromof 7, in the
of

caused a decrease in the proportion 9 ,.tm diameter in the normal group treated nuclei group (8% accordingly.

of nuclei ( 1 % ) and
the proportion

),

and

increased

These to the in the

effects

on

the

nuclear of prolactin rat pituitary and close

DNA

di-

E
:,

6
6..

ameter seem cells believed

gland (21,22).

large in relation to be present

small number normal male

05
z

The serum
ciations

correlations prolactin
between

are

of MND with DNA synthesis highly significant, indicating

variables. It appears that

with assosyn-

these

I.

L*

ns

ns
C

ns d

ns e

**

thesis both increased not

and

secretory MND. by haloperidol

activity, alone, from

whether which treatment

inhibited nuclear stimulated with

or stimulated, diameter was not but and secretion estrogen

influence

However,

Figure 2. Mean nuclear diameter (MND) of all nuclei (black circles) and of tritiated-labeled nuclei (open circles) for each group. (a) bromocniptine; (b) estrogen + bromocniptine; (c) haloperidol; (d) vehicle; (e) estrogen; (I) estrogen + haloperidol. Students t test between labeled and unlabeled MND for each group, #{176} <0.001, p ns-not significant. Correlation coefficient: r = +0.78 (ns). r = +0.97 (P

DNA synthesis. The MND resulting was higher the effects

bromocriptine mechanisms.

bromocniptine alone. Hence

inhibited dopaminergic by

than that of estrogen

and The may

found with bromocniptine alone were not entirely

have been action unrelated of estrogen to

mitogenic

<0.01)

when

the bromocriptine

group

is omitted.

extends other the genital

to all pituitary target

used

cell remote results

cells

types from raise

other

and the the

than

estrogen possibilities
prolactin

is mitogenic such a) that

cells, b)

in as the
that

tissues tract.
act

hypothalamus,

The
on

(2) in

and prolactin

that

it stimulates cells the a finding dopamine

secretory

activity

and

proliferation

agents

(2 1 ). Bromocniptine prolactin-secreting confirmed antagonist by

is believed
cells staining pimozide of (20). (20), may the

to suppress
anterior Halopenidol, appears also stimulate to pi-

dopaminergic of cell mediated

addition,

effects

on

pituitary

cell

nuclei other in these

in nuclear

occur

regardless In
may

predominantly tuitary like (14), another

type, and c) that mechanisms ones affected nuclear size

the extent of the change

than dopamineexperiments.
diameter

act mainly other

on the prolactin of the

cells

( 1 5 , 1 1 ), but

mean
previous The provide

that

prolactin-secreting
data suggest.

cells

are

more

numerous cells

than

cell types. The histograms

distribution

of the

size

of nuclear

nuclear further

diameters
relevant

of tritiated-labeled
information. Thus,

(S phase)
correlation

diameters (Figure 1 ) show some skewness to the left. As suggested under Materials and Methods, some of the skew distnibution may be explained by section thickness especially in

the

between

nuclear

diameters

in labeled

and

unlabeled

cells

sug-

glands reduce groups. clei the

ably

with the were control

on

large

nuclei. increased

If anything, observed nuclear

skewness between size such

would the that 59%

tend treatment

to

differences

gests that the diameter of S-phase nuclei is determined by the diameter of the majority of the nuclei present in the tissue (non-S phase). The lack ofenlargement associated with a pure increase increase in secretion when S-phase (halopenidol nuclei are effect) present contrasts (estrogen). with The the in-

Estrogen

of flu-

7, 8, and 9 .tm in diameter, compared to 19% in group (see Table 2). Halopenidol, acting presumprolactin cells (15

), further

increased

the

proportion

crease in MND ence of S-phase

with estrogen nuclei, these

is not attributable being few in number,

to the presand could

Table

3.

Correlation

coefficients MND (6).

(r values)
Nuclear

between

the

pairs DNA

of variables synthesis

indicated (6) Mitotic index (4) Label index (6) Serum prolactin (6)

area (6)

MND Nuclear

(6) area (6)

1.00 0.81 1.00

DNA
Mitotic

synthesis
index (4)

(6)

0.97

0.86

1.00

0.72 0.95

0.94 0.81

0.90 0.94

1.00 0.87 1.00

Label Serum

index

(6) (6)

prolactin

0.93

0.95

0.95

0.89

0.88

1.00

The

number

of samples

in each

group

is noted

in parentheses.

<

0.05,

<

0.01.

NUCLEAR

DIAMETER

IN

THE

RAT

PITUITARY

GLAND

681

be and

explained
late

by may

a phase
largest

not

found
MND

with
found

halopenidol
with halopenidol

only, in late

7.

Fand
perplasia

SB: Polyploidy
and hypertrophy.

possibly

G 1. The

in the human pituitary: coexistence Am J Pathol 70:61a, 1973 JF: Electron

of castrate

of hyof the
54:516,

estrogen

be explained

by an increase the

of cells notably presence

8. Farquhar
anterior 1954

MG,
pituitary

Rinehart
gland

microscopic
rats. Endocrinology

studies

Gi or pre-S phase, since this combination DNA synthesis. In the other direction, reduced reduction
mal, fecting spares not

stimulates of nuclei

in size (bromocriptine) in DNA synthesis,

reduced, diameter. of that a high a group proportion of cells

is associated with a significant but S-phase nuclei were of norThus, pituitary able bromocniptine, cells to (lowering enter S phase while MND), with af-

9. GrafKJ, Horowski R, El Etreby MF: Effect ofprolactin inhibitory agents on the ectopic anterior pituitary and the mammary gland in rats. Acta Endocninol 85:267, 1977
10. Jacobi JM, Lloyd HM, Meares JD: Onset of oestrogen-induced prolactin secretion and DNA synthesis by the rat pituitary gland. J Endocninol 72:35, 1977 Jacobi JM, Lloyd 33:97, HM: 1981 Modulation by dopamine antagonists of

remains

a normal Our
allowed us

nuclear absorbance
to draw

diameter. measurements
no conclusions

of
on

Feulgen-stained
pituitary DNA

nuclei
content.

1 1.

DNA

synthesis J, Herlant
and

in the pituitary M, Duclos

acid 1967 content

gland

of the male

rat. Neuroen-

docninology

On

the

other
the

hand,
large size

the

relation

of nuclear
seen in the

diameter
present

to ploidity
experiments,

12.

( 3 ) and suggests estrogen tumors tumors (6). Note attention

of nuclei

Kraicer cytology Pharmacol

P: Changes
in the

in adenohypophyseal
rat 32 days after bilateral

nucleic 45:947,

that polyploidy may action. Polyploidy induced (7),

and

be present has been in the

isolated from

at this observed
rat

early in

stage of pituitary pituitary

tumors
14.

adrenalectomy

and the chronic

MearesJD,JacobiJM:

injection
Early

ofcortisol.
effects

CanJ
ofstilboestrol

Physiol
on

by estrogen
in GH3 cells

rat (23),

in human
pituitary

13.

Lloyd

HM,

growth
activity

hormone
in the

and prolactin secretion and on pituitary male rat. J Endocninol 58:227, 1973
and Effects mitosis ofoestrogen in prolactin

mitotic

added in proof. has been drawn

Since to the

this paper was article by Poole 1980) was a rise

submitted our MC, Mahesh nuclear during volume

15.

Lloyd HM, MearesJD,JacobiJM: ocriptine on in vivo secretion (Lond) 255:497, 1975 Lloyd
77:129,

and bromcells. Nature

VB, Kostoff A (Am volume in rat pituitary the

with

J Anat

158:3, mammotropes in particular

in which measured in nuclear

HM,JacobiJM,
1978

MearesJD:

DNA

synthesis

and

depletion

of prolactin
16.

in the pituitary
Cooke

gland
RA:

of the male
Nuclear

rat. J Endocrinol
in parathy-

estrus
rising

cycle,
estradiol

showing
levels.

Lloyd HM,JacobiJM, roid adenomas. J Clin Lloyd HM, Jacobi JM, synthesis and secretory Endocrinol 96:70, 1981

diameter

Pathol
Willgoss activity

32:1278,

1979
J, Ward
adenomas.

1 7.

Literature
1.

Cited

D, Kearney in parathyroid

P: DNA
Acta

Antakly T, Pelletier G, Zeytinoglu F, Labrie F: Changes of cell morphology and prolactin secretion induced by 2-Br-ergocniptine, estradiol, and thyrotropin-releasing hormone in rat anterior pituitary cells in culture. J Cell Biol 86:377, 1980 Attramadal pophysis. A: Cellular Z Zellforsch localization of H-oestradioI Mikrosk Anat 104:597, in the by-

18. Pawlikowsky
morphine
tomized

M, Kunert-Radek J: Effects of estradiol and apoon the anterior pituitary cell proliferation in ovaniecfemale rats. Neuroendocrinol Lett 4:229, 1980 Histochemistry.J
anterior 1978
& A

19. 20.

Pearse Stepien

AGE:

Churchill
cell

Ltd., London,

1968

2.

1970
DNAnormal

H, Wolaniuk
on 42:239,

A, Pawlikowski
pituitary

M: Effects

3.

Bengtsson A, Grimelius L,Johansson H, PontenJ: Nuclear content ofparathyroid cells in adenomas, hyperplastic and glands. Acta Pathol Microbiol Scand 85A:455, 1977

bromocniptine Transmiss

ofpimozide and proliferation. J Neural transforrat. Cell Tissue

21. Stratmann

IE, Eznin

C, Sellers
into

EA:

Estrogen-induced
in the

4. Brachetj,
York, 1961,

Minsky K: A study

AE, Eds: The Cell, vol 5. Academic

413-4 14

Press,

New

mation ofsomatotrophs Res 152:229, 1974

mammotrophs

p 49-64,

5. Burton

of the conditions
for colorimetric 62:315, 1956

and mechanism
estimation of

of the dideoxynibo-

22. Surks

phenylamine nucleic acid.

reaction BiochemJ

MI, Defesi CR: Determination of the cell number of each cell type in the anterior pituitary of euthyroid and hypothyroid rats. Endocrinology 101:946, 1977 les oestrogenes
5:119, 1969

6. Clausen
growth mone

23. Waelbroeck-Van
T: Cell cycle distributions,
horArch and growth Virchows

OPF,

Gautvik

KM,

Lindmo

Gayer C: Tumeurs chez le rat. II Etude

hypophysaires cytogenetique.

induites par EurJ Cancer

characteristics, production

and variation in prolactin in cultured rat pituitary cells.

Cell

Pathol

23:195,

1977