Endocrine Research
ISSN: 0743-5800 (Print) 1532-4206 (Online) Journal homepage: http://www.tandfonline.com/loi/ierc20
Effect of Reserpine on the Inhibition of Prolactin Released from Different Pituitary Constructs in Vitro by Dopamine, Bromocriptine and Apomorphine A. Dutt & H. S. Juneja To cite this article: A. Dutt & H. S. Juneja (1992) Effect of Reserpine on the Inhibition of Prolactin Released from Different Pituitary Constructs in Vitro by Dopamine, Bromocriptine and Apomorphine, Endocrine Research, 18:4, 307-320, DOI: 10.1080/07435809209111039 To link to this article: http://dx.doi.org/10.1080/07435809209111039
Published online: 12 May 2012.
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Date: 26 April 2016, At: 07:49
ENDOCRINE RESEARCH, 18(4), 307-320 (1992)
EFFECT OF RESERPINE ON THE INHIBITION OF PROLACTIN RELEASED FROM DIFFERENT PITUITARY CONSTRUCTS
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I N V I T R O BY DOPAMINE, BROMOCRIPTINE AND APOMORPHINE
D u t t , A. and H.S.Juneja* D i v i s i o n o f Neuroendocrinology, I n s t i t u t e f o r Research i n Reproduction ( I C M R ) , P a r e l , Bombay 400 012, INDIA.
ABSTRACT Hourly release of Prolactin by pituitary constructs : whole pituitary (PI) , adenohypophysis (P-N) and pituitary-hypothalamus co-incubate
(PHC)
were
compared.
Adenohypophysis
secreted
significantly more prolactin than PI and PHC, while PHC secreted significantly l e s s than PI.
Co-incubation of (P-N) with posterior
pituitary reduced t h e elevated secretion of prolactin. of
dopamine
( 5 x 10-8M)
(lOV7M),
bromocriptine
( 10-7M)
and
Addition
apomorphine
to these constructs d i d not affect t h e release of
"Correspondence t o ' b e addressed 307 Copyright 0 1992 by Marcel Dekker, Inc.
DUTT AND JUNEJA
308 prolactin from PI but inhibited the same Treatment
with
reserpine increased
from (P-N)
serum prolactin
intrapituitary prolactin contents w e r e decreased. of
prolactin
from pituitary
constructs
treated r a t s was significantly acid
-
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inhibited
perphenazine
Hourly release
derived from reserpine-
reduced as compared to ascorbic
and apomorphine ( 5 x 10-8M)
prolactin
secretion
stimulated
the
PHC.
levels but
Inclusion of dopamine ( 1O-.'M),
treated controls.
criptine ( 1 0 - 7 M )
and
In
further. release
of
i n these constructs
vitro
prolactin
was without any effect on PI and (P-N).
bromo-
addition by
of
PHC
but
The data are inter-
preted to suggest that dopamine i n posterior
pituitary may be
an important determinant of hypothalamic modulation of prolactin secretion.
INTRODUCTION
G i l l et al. hypothalamus
( 1 ) proposed a model for studying pituitary-
interactions
pituitary-hypothalamus retaining the
natural
pituitary.
effectively
in-vitro,
complex
anatomic
this
system,
(PHC)
is
dissected
orientation
of
the
Dutt et al.
inhibited the
In
(2)
rat
a
unit
hypothalamus
observed t h a t
release of
as
the
dopamine
to
(DA)
PRL from PHC but failed
to inhibit its secretion from whole pituitary
( P I ) or PI plus
hypothalamus co-incubate with severed neural linkages. The available effectively
blocks
i n v i t r o (3-11).
literature is replete with reports t h a t DA PRL
release
from
adenohypophysis
Neurohypophysis contains DA (12,13).
(P-N)
Evidence
309
PROLACTIN RELEASE IN VImO
e x i s t s that DA of neurohypophysial origin inhibits tonic secretion
Bergland and Page ( 1 5 ) have demonstrated profuse
of PRL (14).
vascularization of the posterior pituitary and a crossed circulation
of
blood flow from posterior pituitary t o adenohypophysis and Earlier interconnections between t h e posterior pitui-
vice-versa. tary
and
the
adenohypophysis
via
short
hypophysial
vessels
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had been demonstrated by Landsrneer (16) and Daniel and h i t -
chard ( 1 7 ) . and
Thus communication between neurohypophysial cells
adenohypophysial
regulatory
factors
diffusion respond
cells can take place via t h e release of
into
the
short
portal
may
be
then the removal of
become
responsive
depletes brain
of
to
If t h i s t h e s i s
to
PI.
In
secretion of PRL by
inhibition
by
exogenous
(P-N)
DA.
such should
Reserpine
its catecholamine contents including DA
The depletion
21).
their
neurophypophysis should increase
the secretion of PRL by (P-N) as compared a circumstance, the elevated
by
due t o restraining effect of
endogenous DA on PRL secretion from lactotropes. is t r u e ,
or
The inability of PI to
into t h e intercellular space. to exogenous DA
vessels
of
endogenous
hypothalamic
(18-
and posterior
pituitary DA should therefore render PI responsive t o inhibition by exogenous DA. to in-vivo
Moreover, i f PHC is a viable model responding
manipulations
should e l i c i t responses
induced by
pharmacologic
appropriate i n
terms
of
agents,
PHC
PRL secretion
i n vitro. In the present communication, we have compared the pattern of
PRL
released
by
PI
and
(P-N)
system.
In addition,
we
3 10 have
DUTT AND JUNEJA tested
the
effect
of
treatment
of
adult
male
rats
with
reserpine on the secretion of PRL from PI, P-N or PHC in vitro. Attempts
were also also made to compare effects of
of
additions
dopamine,
bromocriptine
and
in v i t r o
apomorphine
on PRL
released by different constructs with or without reserpine treat-
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ment.
MATERIALS AND METHODS Animals : used. with
Holtzman strain male r a t s weighing 200-250
g were
These rats were maintained i n an air-conditioned
facility
temperature
varying
ranging from 50 to 56%. and 10 h darkness.
22
from
to
24OC
and
the
humidity
The light schedule was 14 h light
The animals w e r e fed a pelleted d i e t with
water ad-libitum.
of tissue
Dissection
Pituitary-hypothalamus
:
was dissected as described e a r l i e r ( 1 ) . by decapitation.
complex
(PHC)
The r a t s were killed
Brains were exposed by a dorsal incision.
The hypothalamic
island
was demarcated by cutting along the
lateral hypothalamic sulci, posterior edge of the optic chiasma and the anterior edge of the mammillary bodies. lamic island attached was lifted was
by
carefully
to the pituitary
an undercut scooped
2
via hypophysial s t a l k
mm deep.
from sella turcica
adhering
ligaments.
Where
desired,
the neurointermediate
the
The hypotha-
The pituitary after freeing
adenohypophysis
lobe
it of
(P-N) was
(posterior pituitary)
carefully pinched using a p a i r of fine forceps.
(PI)
was
PROLACTIN RELEASE IN VITRO
311
Reserpine injections : Rats were injected with reserpine a t a dose level of 1.5 group
received
m g / r a t i n 25% ascorbic acid.
ml
0.24
25% ascorbic
acid.
S.C.
Control
The r a t s were
decapitated 46 h later.
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and
DA ,
of
Solutions
perphenazine Ascorbic at
:
Reserpine
a
were
Apomorphine, Bromocriptine , Perphenaxine Dopamine,
apomorphine , bromocriptine
dissolved
in
acid served a s an
final
concentration
of
bromocriptine , apomorphine
ascorbic
.05%
anti-oxidant per
.05% and
agent
-7 M, 10-7M,
solution.
and was used
incubation.
perphenazine
Dopamine,
were
tested
at
and 5 x 10F8M,
8 x 10-8M
final concentrations of 10
acid
and
respectively,
Incubation
conditions :
Dulbecco I s
(DMEM) fortified with non-essential
modified
Eagle I s
medium
amino acids, 3 mM NaHC03
and .01 M Hepes (4-( 2-hydroxyethy1)-1-piperazine-ethane sulfonic
was
acid) plastic
used,
Incubations were
(Laxbro,
capacity each.
Pune,
done a t
India) t r a y s
with
37OC i n Laxbro-
24
Each well contained 1 m l DMEM.
Freshly dissec-
ted tissues were transferred into individual wells, were
preincubated
for
1 h
after
which
the
5 ml
of
wells
The contents
spent
incubation
medium was replaced with 1 m l of f r e s h medium and t h e contents incubated
further.
times by
removing t h e tissue from the incubation w e l l .
tissue spent
was
blotted
incubation
The
and
incubation
weighed
on
medium from each
was
a
stopped
torsion
well
was
at
desired The
balance.
The
transferred
into
D U l T AND JUNETA
312
individual ,tubes and stored at -30'
until assayed for PRL by
RIA.
Hormone Assay : PRL was assayed a s p e r the procedure described in
the
NIH,
brochure
Bethesda,
supplied
by
the
National
Pituitary
The standard curve for PRL
M.D.
Agency, (NIAMDD-
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Rat-PRL-RP-2) ranged from 1 0 pg t o 12.5 ng p e r assay tube. Interassay
and intraassay variations
for PRL were
14 and 5%
respectively ( 2 ) .
S t a t i s t i c a l Analysis
:
The
analysis of variance.
data
were
analysed
by
one-way
The differences between the groups were
computed u s i n g Duncan I s multiple range test.
RESULTS Comparative secretion of + PP :
(Table I)
PHC,
(P-N) and (P-NL
PRL by PHC, PI, PI,
(P-N)
and (P-N)
+ PP constructs
secreted significantly more PRL during t h e first hour incubation than
during
The
amount
subsequent
of
3rd
and
PRL released p e r h
its respective 2nd, rable.
2nd,
4th by
hourly
each
incubations.
construct
during
3rd and 4th hourly incubations was compa-
A t every hourly incubation period (P-N) secreted signifi-
cantly more PRL than PI, PHC or (P-N) + PP, while PHC secreted significantly
less
PI
or
(P-N)
+ PP.
Go-incubation
of
(P-N)
+ PP reduced t h e amount of PRL secreted by (P-N) d u r i n g each hourly incubation period.
Effect of re s e r p i n e injections on serum and intrapituitary
levels : (Table 11)
Reserpine
reduced
the
PRL
intrapituitary
I
50*a
21a
f
5
b
*
124 f 16
288 f 23
140 f 8b
87
2nd h
ng NIADDK-Rat-PRL-RP-2
b
* 9
130 f 1 3
248 f 17
122
*
80 +- 10
3rd h
135
*,
s i g n i f i c a n t l y d i f f e r e n t w.r.t.
c o r r e s p o n d i n g PI, PHC a n d (P-N)
+
*
PP ( p o s t e r i o r p i t u i t a r y ) .
b, s i g n i f i c a n t l y d i f f e r e n t w i t h respect t o c o r r e s p o n d i n g PI ( P c .05) a n d (P-N) ( P q .05).
a, s i g n i f i c a n t l y d i f f e r e n t f r o m respective 2nd, 3rd a n d 4 t h hour incubation.
5
+-
18
*
13
9b
260 2 24
138
80
4th h
E a c h group has atleast
released m l-1 h-l
E x p e r i m e n t a l details are as described u n d e r "Materials and Methods1'. 1 0 i n d i v i d u a l incubations. Values are expressed a5 Mean k S.D.
I
f
f
266 f 17a
478
P-N
P-N + PP
h
115 f 14ab
186
I
1st
PI
PHC
System
-
COMPARATIVE RELEASE OF PRL BY DIFFERENT CONSTRUCTS IN VITRO
TABLE
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DUTT AND JUNEJA
314
TABLE
-
I1
EFFECT OF RESERPINE INJECTION ON THE INTRAPITUITARY CONTENT
AND SERUM PRL LEVELS
TREATMENT P e r m l serum
Per Pituitary
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9 4 2
1303 4 2 5 6
None
Ascorbic Acid Reserpine (1.5 mgirat) No,of animals p e r group = 12. Values a r e expressed as MeankS.D. different with respect to controls with and without ascorbic acid ( P c .05).
* Significantly
contents
of
PRL but
increased
serum
PRL levels
markedly
as
compared to controls receiving no reserpine.
Effect of reserpine on the release of PRL by different pituitary constructs i n vitro : (Table 111)
( 2 5 % ) ascorbic a c i d ,
ml
with 0.24
more PRL than PI.
PI or PHC,
Dopamine, bromocriptine
In
control
(P-N)
group
injected
secreted significantly
while PHC secreted less PRL than or apornorphine addition i n v i t r o
elicited no effect on the release of PRL by PI,
but inhibited
the release of PRL significantly by (P-N) and PHC, a s compared to corresponding release
of
controls.
PRL
by
Perphenazine
PI
release significantly by PHC Reserpine
reduced
or
had
(P-N),
no effect on the
but
stimulated
its
secreted
by
.
the
amount
of
PRL
PI, (P-N) or PHC system as compared t o control group injected
-
f
f
393
f
317
364
f
344
32
694
108
339
32
16
219
39
f
f
f
f
12'
17a
17a
36a
702 f 27'
429 k 47 f
24
466
188
161
f
f
f
18
*
37a
16a
124 k 9a
316
PHC f
6b
140
40
46
f
f
f
12
qab
8ab
50 f 4 ab
126
PI
140
60
f
f
22
8ab
f
k
ab
*
4
gab
gab
330 f 18
30
50
k
167 f 14bC
56 f 12ab
12
59
?r
PHC
12ab
71
126
P-N
Reserpine (25% Ascorbic Acid)
INCUBATION MEDIUM
*,
E x p e r i m e n t a l details are as described u n d e r "Materials and Methods". E a c h v a l u e i s derived f r o m 10 i n d i v i d u a l i n c u b a t i o n s a n d is expressed as Mean k S.D. it, s i g n i f i c a n t l y d i f f e r e n t w i t h respect t o c o n t r o l incubation w i t h .05% ascorbic acid ( P Q .05). b, s i g n i f i c a n t l y d i f f e r e n t f r o m c o r r e s p o n d i n g g r o u p s i n c o n t r o l s treated w i t h 0.24 ml 25% ascorbic acid ( P q .05). c , s i g n i f i c a n t l y d i f f e r e n t w i t h respect to PI a n d PHC of the same g r o u p ( P 6 . 0 5 ) . s i g n i f i c a n t l y d i f f e r e n t w i t h respect t o PI a n d (P-N) of the s a m e g r o u p .
( 5 x lO-*M)
Perphenazine
(IO-~M)
Bromocriptine
(.05%)
Ascorbic acid
P-N
PI
Control (25% Ascorbic Acid)
ng NIADDK-Rat-PRL-RE'-3
XI1 : EFFECT OF S.C. RESERPINE INJECTION ON THE RELEASE OF P R L BY DIFFERENT PITUITARY CONSTRUCTS IN VITRO.
Additions (in vitro)
TABLE
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DUTT AND JUNEJA
3 16 with 0.24
m l 25% ascorbic acid.
Dopamine, bromocriptine and
apornorphine additions i n vitro reduced the amount of PRL secreted by PI, (P-N) and PHC systems. on
PRL
secretion
by
PI
or
Perphenazine was without effect (P-N)
but
stimulated
its release
significantly by PHC.
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DISCUSSION A
significant
observation
made
during t h e
present
study
was that (P-N) secreted significantly more PRL than PI or PHC. Co-incubation by (P-N).
The r e s u l t s suggested t h a t removal of PP m u s t have
eliminated by
of (P-N) + PP reduced the amount of PRL released
endogenous
lactotropes.
DA
that
restrained
the
release
of
Evidence is also available for the presence
of prolactin releasing factor( s ) i n the posterior pituitary
In
that
reduced
case,
PRL
elimination
prolactin
of
secretion
posterior instead
of
pituitary
(22).
should
have
it.
The
augmenting
fact that PRL secretion was enhanced by removal of posterior pituitary gives credence t o the central role of posterior pituit a r y DA i n the regulation of PRL secretion.
I t is of interest
to note that dopamine and its agonists reduced t h e secretion of
PI.
PRL
by
(P-N)
but
failed to affect
secretion
of
PRL by
O u r data with (P-N) a r e i n agreement with e a r l i e r observa-
The data to u s s u g g e s t that exogenous dopamine
tions (3-11).
and its agonists were probably effective i n reducing t h e stimulated release of
i n reducing
the
newly synthesized basal
secretion.
PRL but
were not effective
This view is strengthened
PROLACTIN RELEASE IN VZl7?0 by
the
than
observation
(P-N)
that
secreted
PHC
or PI and
exogenous
significantly
dopamine
reserpine
increased
pituitary
PRL content.
serum
e a r l i e r observations
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(24),
its
and
were not effective i n reducing PRL secretion.
l e s s PRL agonists
Treatment with
PRL l e v e l s but reduced the intra-
These f i n d i n g s a r e i n agreement with
Graf et al.
of
(23).
Horowski and Graf
Lu et al. (25) and Gudelsky and Meltzer ( 2 6 ) . Another
significant
treatment PI, (P-N)
f i n d i n g was t h a t following reserpine
and PHC secreted l e s s PRL than correspond-
ing controls. The reduced secretion of PRL by (P-N),
PHC and
PI may be a reflection of lowered intrapituitary PRL contents. Interestingly,
here
dopamine
and
its agonists
were
effective
i n reducing PRL secretion by PHC and PI i n addition t o
(P-N).
This lends credence to the theory that depletion of endogenous DA rendered PI or PHC amenable to inhibition of PRL secretion
by
DA.
exogenous
As
an appropriate model
a
corollary
(P-N)
then
for studying t h e effect of
is
not
dopamine and
its agonists on the basal secretion of PRL, because what one measures
is t h e effect of exogenous dopamine and its agonists
on t h e exaggerated or stimulated removal or deprivation of PP. model for the
study of
release of
PRL unleashed
by
In our opinion, t h e appropriate
basal secretion of
PRL would be PI.
Since PHC secreted l e s s PRL than PI, it suggests t h a t PHC elaborated
endogenous
PRL as compared
PIF
(dopamine)
to PI,
anatomic topography
that
Since i n
in relation
reduced
PHC
the
release of
pituitary
retains its
t o hypothalamus
and responded
DU'IT AND JUNEIA
318
to i n vitro release,
perphenazine
addition
with
stimulated
prolactin
PHC is a model of choice for studying hypothalamus
pituitary interactions i n vitro.
ACKNOWLEDGMENT
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We
gratefully
acknowledge
receiving the
.
PRL from NIAMDD,
Bethesda , U S .A.
help
Mrs.Annette
rendered
by
RIA
K i t for r a t
We appreciate invaluable
Fonseca
in
drafting
and
final
typing of the manuscript.
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G u d e l s k y DA, Porter JC. 1979. Release of n e w l y s y n t h e s i z e d dopamine i n t o the h y p o p h y s i a l portal v a s c u l a t u r e of t h e rat. Endocrinology 104 : 583-587.
Vessels of t h e r a t ' s h y p o p h y s i s .
.
320
DUTT AND JUNFJA
19. Umezu K , Moore KE.
1978. Effects of drugs on regional brain concentrations of dopamine and dihydroxyphenyl acetic acid. J Pharmacol Exp Therap 208 : 49-55.
20. Fekete M I K , Szentendrei T , Herman J P , Kanyicska B. 1980.
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Effects of reserpine and antidepressants on dopamine and DOPAG ( 3,4-dihydroxyphenylacetic acid) concentrations i n the striatum olfactory tubercle and median eminence of r a t s , E u r J Pharmacol 64 : 231-238.
21.
Demarest KT, Moore KE. 1981. Sexual differences i n the sensitivity of tuberoinfundibular dopamine neurons to the action of prolactin. Neuroendocrinology 33 : 230-234.
22.
Dymshitz J , Ben-Jonathan N. 1991. Co-culture of anterior and posterior pituitary cells : Selective stimulation of lactotropes. Endocrinology 128 : 2469-2475.
23,
Graf K J , Neumann F , Horowski R. 1976. Effect of the ergot derivative lisuride hydrogen maleate on s e r u m prolaci n concentrations i n female rats. Endocrinology 98 : 598-
605. 24. Horowski R,
Graf K J , 1976. Influence of dopaminergic agonists and antagonists on s e r u m prolactin concentrations i n the rat. Neuroendocrinology 22 : 273-286.
Amenomeri Y, Chen CL, Meites J. 1970. Effects of central acting drugs on s e r u m and pituitary prolactin levels i n rats. Endocrinology 87 : 667-672.
25. Lu K H ,
Meltzer HY. 1984. Function of tuberoinfundibular dopamine neurons i n pargyline and reserpine treated rats. Endocrinology 38 : 51-55.
26. Gudelsky GA,
ISSN: 0743-5800 (Print) 1532-4206 (Online) Journal homepage: http://www.tandfonline.com/loi/ierc20
Effect of Reserpine on the Inhibition of Prolactin Released from Different Pituitary Constructs in Vitro by Dopamine, Bromocriptine and Apomorphine A. Dutt & H. S. Juneja To cite this article: A. Dutt & H. S. Juneja (1992) Effect of Reserpine on the Inhibition of Prolactin Released from Different Pituitary Constructs in Vitro by Dopamine, Bromocriptine and Apomorphine, Endocrine Research, 18:4, 307-320, DOI: 10.1080/07435809209111039 To link to this article: http://dx.doi.org/10.1080/07435809209111039
Published online: 12 May 2012.
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Date: 26 April 2016, At: 07:49
ENDOCRINE RESEARCH, 18(4), 307-320 (1992)
EFFECT OF RESERPINE ON THE INHIBITION OF PROLACTIN RELEASED FROM DIFFERENT PITUITARY CONSTRUCTS
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I N V I T R O BY DOPAMINE, BROMOCRIPTINE AND APOMORPHINE
D u t t , A. and H.S.Juneja* D i v i s i o n o f Neuroendocrinology, I n s t i t u t e f o r Research i n Reproduction ( I C M R ) , P a r e l , Bombay 400 012, INDIA.
ABSTRACT Hourly release of Prolactin by pituitary constructs : whole pituitary (PI) , adenohypophysis (P-N) and pituitary-hypothalamus co-incubate
(PHC)
were
compared.
Adenohypophysis
secreted
significantly more prolactin than PI and PHC, while PHC secreted significantly l e s s than PI.
Co-incubation of (P-N) with posterior
pituitary reduced t h e elevated secretion of prolactin. of
dopamine
( 5 x 10-8M)
(lOV7M),
bromocriptine
( 10-7M)
and
Addition
apomorphine
to these constructs d i d not affect t h e release of
"Correspondence t o ' b e addressed 307 Copyright 0 1992 by Marcel Dekker, Inc.
DUTT AND JUNEJA
308 prolactin from PI but inhibited the same Treatment
with
reserpine increased
from (P-N)
serum prolactin
intrapituitary prolactin contents w e r e decreased. of
prolactin
from pituitary
constructs
treated r a t s was significantly acid
-
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inhibited
perphenazine
Hourly release
derived from reserpine-
reduced as compared to ascorbic
and apomorphine ( 5 x 10-8M)
prolactin
secretion
stimulated
the
PHC.
levels but
Inclusion of dopamine ( 1O-.'M),
treated controls.
criptine ( 1 0 - 7 M )
and
In
further. release
of
i n these constructs
vitro
prolactin
was without any effect on PI and (P-N).
bromo-
addition by
of
PHC
but
The data are inter-
preted to suggest that dopamine i n posterior
pituitary may be
an important determinant of hypothalamic modulation of prolactin secretion.
INTRODUCTION
G i l l et al. hypothalamus
( 1 ) proposed a model for studying pituitary-
interactions
pituitary-hypothalamus retaining the
natural
pituitary.
effectively
in-vitro,
complex
anatomic
this
system,
(PHC)
is
dissected
orientation
of
the
Dutt et al.
inhibited the
In
(2)
rat
a
unit
hypothalamus
observed t h a t
release of
as
the
dopamine
to
(DA)
PRL from PHC but failed
to inhibit its secretion from whole pituitary
( P I ) or PI plus
hypothalamus co-incubate with severed neural linkages. The available effectively
blocks
i n v i t r o (3-11).
literature is replete with reports t h a t DA PRL
release
from
adenohypophysis
Neurohypophysis contains DA (12,13).
(P-N)
Evidence
309
PROLACTIN RELEASE IN VImO
e x i s t s that DA of neurohypophysial origin inhibits tonic secretion
Bergland and Page ( 1 5 ) have demonstrated profuse
of PRL (14).
vascularization of the posterior pituitary and a crossed circulation
of
blood flow from posterior pituitary t o adenohypophysis and Earlier interconnections between t h e posterior pitui-
vice-versa. tary
and
the
adenohypophysis
via
short
hypophysial
vessels
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had been demonstrated by Landsrneer (16) and Daniel and h i t -
chard ( 1 7 ) . and
Thus communication between neurohypophysial cells
adenohypophysial
regulatory
factors
diffusion respond
cells can take place via t h e release of
into
the
short
portal
may
be
then the removal of
become
responsive
depletes brain
of
to
If t h i s t h e s i s
to
PI.
In
secretion of PRL by
inhibition
by
exogenous
(P-N)
DA.
such should
Reserpine
its catecholamine contents including DA
The depletion
21).
their
neurophypophysis should increase
the secretion of PRL by (P-N) as compared a circumstance, the elevated
by
due t o restraining effect of
endogenous DA on PRL secretion from lactotropes. is t r u e ,
or
The inability of PI to
into t h e intercellular space. to exogenous DA
vessels
of
endogenous
hypothalamic
(18-
and posterior
pituitary DA should therefore render PI responsive t o inhibition by exogenous DA. to in-vivo
Moreover, i f PHC is a viable model responding
manipulations
should e l i c i t responses
induced by
pharmacologic
appropriate i n
terms
of
agents,
PHC
PRL secretion
i n vitro. In the present communication, we have compared the pattern of
PRL
released
by
PI
and
(P-N)
system.
In addition,
we
3 10 have
DUTT AND JUNEJA tested
the
effect
of
treatment
of
adult
male
rats
with
reserpine on the secretion of PRL from PI, P-N or PHC in vitro. Attempts
were also also made to compare effects of
of
additions
dopamine,
bromocriptine
and
in v i t r o
apomorphine
on PRL
released by different constructs with or without reserpine treat-
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ment.
MATERIALS AND METHODS Animals : used. with
Holtzman strain male r a t s weighing 200-250
g were
These rats were maintained i n an air-conditioned
facility
temperature
varying
ranging from 50 to 56%. and 10 h darkness.
22
from
to
24OC
and
the
humidity
The light schedule was 14 h light
The animals w e r e fed a pelleted d i e t with
water ad-libitum.
of tissue
Dissection
Pituitary-hypothalamus
:
was dissected as described e a r l i e r ( 1 ) . by decapitation.
complex
(PHC)
The r a t s were killed
Brains were exposed by a dorsal incision.
The hypothalamic
island
was demarcated by cutting along the
lateral hypothalamic sulci, posterior edge of the optic chiasma and the anterior edge of the mammillary bodies. lamic island attached was lifted was
by
carefully
to the pituitary
an undercut scooped
2
via hypophysial s t a l k
mm deep.
from sella turcica
adhering
ligaments.
Where
desired,
the neurointermediate
the
The hypotha-
The pituitary after freeing
adenohypophysis
lobe
it of
(P-N) was
(posterior pituitary)
carefully pinched using a p a i r of fine forceps.
(PI)
was
PROLACTIN RELEASE IN VITRO
311
Reserpine injections : Rats were injected with reserpine a t a dose level of 1.5 group
received
m g / r a t i n 25% ascorbic acid.
ml
0.24
25% ascorbic
acid.
S.C.
Control
The r a t s were
decapitated 46 h later.
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and
DA ,
of
Solutions
perphenazine Ascorbic at
:
Reserpine
a
were
Apomorphine, Bromocriptine , Perphenaxine Dopamine,
apomorphine , bromocriptine
dissolved
in
acid served a s an
final
concentration
of
bromocriptine , apomorphine
ascorbic
.05%
anti-oxidant per
.05% and
agent
-7 M, 10-7M,
solution.
and was used
incubation.
perphenazine
Dopamine,
were
tested
at
and 5 x 10F8M,
8 x 10-8M
final concentrations of 10
acid
and
respectively,
Incubation
conditions :
Dulbecco I s
(DMEM) fortified with non-essential
modified
Eagle I s
medium
amino acids, 3 mM NaHC03
and .01 M Hepes (4-( 2-hydroxyethy1)-1-piperazine-ethane sulfonic
was
acid) plastic
used,
Incubations were
(Laxbro,
capacity each.
Pune,
done a t
India) t r a y s
with
37OC i n Laxbro-
24
Each well contained 1 m l DMEM.
Freshly dissec-
ted tissues were transferred into individual wells, were
preincubated
for
1 h
after
which
the
5 ml
of
wells
The contents
spent
incubation
medium was replaced with 1 m l of f r e s h medium and t h e contents incubated
further.
times by
removing t h e tissue from the incubation w e l l .
tissue spent
was
blotted
incubation
The
and
incubation
weighed
on
medium from each
was
a
stopped
torsion
well
was
at
desired The
balance.
The
transferred
into
D U l T AND JUNETA
312
individual ,tubes and stored at -30'
until assayed for PRL by
RIA.
Hormone Assay : PRL was assayed a s p e r the procedure described in
the
NIH,
brochure
Bethesda,
supplied
by
the
National
Pituitary
The standard curve for PRL
M.D.
Agency, (NIAMDD-
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Rat-PRL-RP-2) ranged from 1 0 pg t o 12.5 ng p e r assay tube. Interassay
and intraassay variations
for PRL were
14 and 5%
respectively ( 2 ) .
S t a t i s t i c a l Analysis
:
The
analysis of variance.
data
were
analysed
by
one-way
The differences between the groups were
computed u s i n g Duncan I s multiple range test.
RESULTS Comparative secretion of + PP :
(Table I)
PHC,
(P-N) and (P-NL
PRL by PHC, PI, PI,
(P-N)
and (P-N)
+ PP constructs
secreted significantly more PRL during t h e first hour incubation than
during
The
amount
subsequent
of
3rd
and
PRL released p e r h
its respective 2nd, rable.
2nd,
4th by
hourly
each
incubations.
construct
during
3rd and 4th hourly incubations was compa-
A t every hourly incubation period (P-N) secreted signifi-
cantly more PRL than PI, PHC or (P-N) + PP, while PHC secreted significantly
less
PI
or
(P-N)
+ PP.
Go-incubation
of
(P-N)
+ PP reduced t h e amount of PRL secreted by (P-N) d u r i n g each hourly incubation period.
Effect of re s e r p i n e injections on serum and intrapituitary
levels : (Table 11)
Reserpine
reduced
the
PRL
intrapituitary
I
50*a
21a
f
5
b
*
124 f 16
288 f 23
140 f 8b
87
2nd h
ng NIADDK-Rat-PRL-RP-2
b
* 9
130 f 1 3
248 f 17
122
*
80 +- 10
3rd h
135
*,
s i g n i f i c a n t l y d i f f e r e n t w.r.t.
c o r r e s p o n d i n g PI, PHC a n d (P-N)
+
*
PP ( p o s t e r i o r p i t u i t a r y ) .
b, s i g n i f i c a n t l y d i f f e r e n t w i t h respect t o c o r r e s p o n d i n g PI ( P c .05) a n d (P-N) ( P q .05).
a, s i g n i f i c a n t l y d i f f e r e n t f r o m respective 2nd, 3rd a n d 4 t h hour incubation.
5
+-
18
*
13
9b
260 2 24
138
80
4th h
E a c h group has atleast
released m l-1 h-l
E x p e r i m e n t a l details are as described u n d e r "Materials and Methods1'. 1 0 i n d i v i d u a l incubations. Values are expressed a5 Mean k S.D.
I
f
f
266 f 17a
478
P-N
P-N + PP
h
115 f 14ab
186
I
1st
PI
PHC
System
-
COMPARATIVE RELEASE OF PRL BY DIFFERENT CONSTRUCTS IN VITRO
TABLE
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DUTT AND JUNEJA
314
TABLE
-
I1
EFFECT OF RESERPINE INJECTION ON THE INTRAPITUITARY CONTENT
AND SERUM PRL LEVELS
TREATMENT P e r m l serum
Per Pituitary
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9 4 2
1303 4 2 5 6
None
Ascorbic Acid Reserpine (1.5 mgirat) No,of animals p e r group = 12. Values a r e expressed as MeankS.D. different with respect to controls with and without ascorbic acid ( P c .05).
* Significantly
contents
of
PRL but
increased
serum
PRL levels
markedly
as
compared to controls receiving no reserpine.
Effect of reserpine on the release of PRL by different pituitary constructs i n vitro : (Table 111)
( 2 5 % ) ascorbic a c i d ,
ml
with 0.24
more PRL than PI.
PI or PHC,
Dopamine, bromocriptine
In
control
(P-N)
group
injected
secreted significantly
while PHC secreted less PRL than or apornorphine addition i n v i t r o
elicited no effect on the release of PRL by PI,
but inhibited
the release of PRL significantly by (P-N) and PHC, a s compared to corresponding release
of
controls.
PRL
by
Perphenazine
PI
release significantly by PHC Reserpine
reduced
or
had
(P-N),
no effect on the
but
stimulated
its
secreted
by
.
the
amount
of
PRL
PI, (P-N) or PHC system as compared t o control group injected
-
f
f
393
f
317
364
f
344
32
694
108
339
32
16
219
39
f
f
f
f
12'
17a
17a
36a
702 f 27'
429 k 47 f
24
466
188
161
f
f
f
18
*
37a
16a
124 k 9a
316
PHC f
6b
140
40
46
f
f
f
12
qab
8ab
50 f 4 ab
126
PI
140
60
f
f
22
8ab
f
k
ab
*
4
gab
gab
330 f 18
30
50
k
167 f 14bC
56 f 12ab
12
59
?r
PHC
12ab
71
126
P-N
Reserpine (25% Ascorbic Acid)
INCUBATION MEDIUM
*,
E x p e r i m e n t a l details are as described u n d e r "Materials and Methods". E a c h v a l u e i s derived f r o m 10 i n d i v i d u a l i n c u b a t i o n s a n d is expressed as Mean k S.D. it, s i g n i f i c a n t l y d i f f e r e n t w i t h respect t o c o n t r o l incubation w i t h .05% ascorbic acid ( P Q .05). b, s i g n i f i c a n t l y d i f f e r e n t f r o m c o r r e s p o n d i n g g r o u p s i n c o n t r o l s treated w i t h 0.24 ml 25% ascorbic acid ( P q .05). c , s i g n i f i c a n t l y d i f f e r e n t w i t h respect to PI a n d PHC of the same g r o u p ( P 6 . 0 5 ) . s i g n i f i c a n t l y d i f f e r e n t w i t h respect t o PI a n d (P-N) of the s a m e g r o u p .
( 5 x lO-*M)
Perphenazine
(IO-~M)
Bromocriptine
(.05%)
Ascorbic acid
P-N
PI
Control (25% Ascorbic Acid)
ng NIADDK-Rat-PRL-RE'-3
XI1 : EFFECT OF S.C. RESERPINE INJECTION ON THE RELEASE OF P R L BY DIFFERENT PITUITARY CONSTRUCTS IN VITRO.
Additions (in vitro)
TABLE
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DUTT AND JUNEJA
3 16 with 0.24
m l 25% ascorbic acid.
Dopamine, bromocriptine and
apornorphine additions i n vitro reduced the amount of PRL secreted by PI, (P-N) and PHC systems. on
PRL
secretion
by
PI
or
Perphenazine was without effect (P-N)
but
stimulated
its release
significantly by PHC.
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DISCUSSION A
significant
observation
made
during t h e
present
study
was that (P-N) secreted significantly more PRL than PI or PHC. Co-incubation by (P-N).
The r e s u l t s suggested t h a t removal of PP m u s t have
eliminated by
of (P-N) + PP reduced the amount of PRL released
endogenous
lactotropes.
DA
that
restrained
the
release
of
Evidence is also available for the presence
of prolactin releasing factor( s ) i n the posterior pituitary
In
that
reduced
case,
PRL
elimination
prolactin
of
secretion
posterior instead
of
pituitary
(22).
should
have
it.
The
augmenting
fact that PRL secretion was enhanced by removal of posterior pituitary gives credence t o the central role of posterior pituit a r y DA i n the regulation of PRL secretion.
I t is of interest
to note that dopamine and its agonists reduced t h e secretion of
PI.
PRL
by
(P-N)
but
failed to affect
secretion
of
PRL by
O u r data with (P-N) a r e i n agreement with e a r l i e r observa-
The data to u s s u g g e s t that exogenous dopamine
tions (3-11).
and its agonists were probably effective i n reducing t h e stimulated release of
i n reducing
the
newly synthesized basal
secretion.
PRL but
were not effective
This view is strengthened
PROLACTIN RELEASE IN VZl7?0 by
the
than
observation
(P-N)
that
secreted
PHC
or PI and
exogenous
significantly
dopamine
reserpine
increased
pituitary
PRL content.
serum
e a r l i e r observations
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(24),
its
and
were not effective i n reducing PRL secretion.
l e s s PRL agonists
Treatment with
PRL l e v e l s but reduced the intra-
These f i n d i n g s a r e i n agreement with
Graf et al.
of
(23).
Horowski and Graf
Lu et al. (25) and Gudelsky and Meltzer ( 2 6 ) . Another
significant
treatment PI, (P-N)
f i n d i n g was t h a t following reserpine
and PHC secreted l e s s PRL than correspond-
ing controls. The reduced secretion of PRL by (P-N),
PHC and
PI may be a reflection of lowered intrapituitary PRL contents. Interestingly,
here
dopamine
and
its agonists
were
effective
i n reducing PRL secretion by PHC and PI i n addition t o
(P-N).
This lends credence to the theory that depletion of endogenous DA rendered PI or PHC amenable to inhibition of PRL secretion
by
DA.
exogenous
As
an appropriate model
a
corollary
(P-N)
then
for studying t h e effect of
is
not
dopamine and
its agonists on the basal secretion of PRL, because what one measures
is t h e effect of exogenous dopamine and its agonists
on t h e exaggerated or stimulated removal or deprivation of PP. model for the
study of
release of
PRL unleashed
by
In our opinion, t h e appropriate
basal secretion of
PRL would be PI.
Since PHC secreted l e s s PRL than PI, it suggests t h a t PHC elaborated
endogenous
PRL as compared
PIF
(dopamine)
to PI,
anatomic topography
that
Since i n
in relation
reduced
PHC
the
release of
pituitary
retains its
t o hypothalamus
and responded
DU'IT AND JUNEIA
318
to i n vitro release,
perphenazine
addition
with
stimulated
prolactin
PHC is a model of choice for studying hypothalamus
pituitary interactions i n vitro.
ACKNOWLEDGMENT
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We
gratefully
acknowledge
receiving the
.
PRL from NIAMDD,
Bethesda , U S .A.
help
Mrs.Annette
rendered
by
RIA
K i t for r a t
We appreciate invaluable
Fonseca
in
drafting
and
final
typing of the manuscript.
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