BIOI.OGY
OF
14, 115-117
REPRODUCTION
Serum
(1976)
Testosterone
Response Estradiol W.
Department
to Acute
Treated H.
in
MOGER
of Physiology and Daihousie University, Nova Scotia, Canada
Halifax,
LH Treatment
Rats
Biophysics, B3H
4H7
ABSTRACT The effect of 1713-estradiol benzoate (E2 B) treatment on serum LH and FSH concentrations and the acute response of serum testosterone concentrations have been examined in intact adult male rats. E2 B treatment (100 Mg/day for 3 days) did not alter serum LH concentration or testes weights but did lower FSH levels in 1 of 2 experiments. E2 B treatment significantly decreased ventral prostate weights and serum testosterone concentrations. Acute treatment with NIH-LH-B9 (1100 Mg) resulted in significant increases in serum testosterone in both E, B treated and control rats but at all doses tested the serum testosterone concentrations obtained in E2 B treated animals were significantly less than in control animals. This work supports the hypothesis that estradiol has a direct inhibitory effect on testosterone secretion. INTRODUCTION It
has
recently
has
a
the
rat
direct
the
observation
to
et
al.,
of
in
situations
serum
The
present
gate
the
found
of
et al.
al.,
(1974)
is also
undertaken
estradiol the
not
alter
to
de
suppresonly suppressed. to
treatment
testis
NIAMDD Rat Pituitary Distribution Program. The assay procedure followed the protocol supplied with these materials with the exception that 0.1 percent gelatin replaced bovine serum albumin in the assay buffer and the incubation times employed were those of Niswender et al. (1968). Sensitivity of the assays were 4 and 8 ng for LH and FSH respectively. Statistical comparison of testes weight, ventral prostate weight, and serum gonadotropin concentrations between E2 B treated and control groups was by Student’s t test. Statistical treatment of the serum testosterone concentrations was by analysis of variance (Steel and Torrie, 1960). Significant differences have p values
g
cd.0
V
©,
#{149}
2
C N
.o
N
‘5
Sb
The male
eN
a
acute rats
dose
administration
has been related
elevation
concentrations C
-
N
.
2
h
after
of
previously
which
of reach
intraperitoneal
LH
shown
to
adult
to result
serum
in
testosterone
maximum
values
injection
(Moger
by and
‘0
6 N
E
C
o
‘5
I-
n
.
.0
x
Armstrong,
V
V
-
U
0
u
9-
present increased a dose the
dose
1974;
Odell
et
experiments LH serum testosterone dependent manner of
LH
(Fig.
2)
al.,
1974).
In
the
from 1 to 10 pg concentrations in (Fig. 1). Increasing above
10
pg
did
not
SENSITIVITY
TO
LH
IN E2 TREATED
concentration.
20-
0’ C
significantly
ments
may
volved
+
15-
treated
animals
to LH
ability
ability respond
of
the
concentrations the
least
of
experi-
in-
concenof
the
E2 B
exogenously
evidence
that
of
testoster-
inhibition
is a direct
effect
testes
to secrete
the
in
partially
to
is supporting
aspect
the changes
of testosterone
impaired
one
of
small at
inhibition
concentrations
one
at
of estradiol testoster-
one. 10’
ACKNOWLEDGMENTS
LU ‘I,
I
5
0
10
I g
30
result testes
1
NIH-LH-B9
FIG. 2. Serum testosterone after LU. Control groups, treated groups, hatched bars.
open
concentrations 2-4 bars; 17f3-estradiol
in further increases, suggesting were maximally stimulated by
doses.
The
observed LH
serum
in
control
the
different
two
experiments
lots
experiment
were
serum
ment.
of
animals
and
the
increased
and may
not
required
to
The
in
were
agreement
not with
alter
on
however,
of
the
to
the
that
these of
near
the
limit
thus
may
not
the
LH
that
is in
E2 B inhib-
by should
a
direct
be of
of small
of
concentra-
concentrations
discriminate
treat-
treatment
hypothesis
sensitivity
E2 B
E2 B
secretion.
E2B
It
pg)
amount
serum
testes.
treat(1
both
concentrations the
LH
tested
thus
by
In
depressed
minimum
that
the each
assays.
testosterone
altered
in
from
LU in
stimulate
testosterone
effect
used
separate
animals,
observation
tions
were
testosterone control
is no except
significantly dose
10 pg
difference
response
lowest serum
treated
with There
samples
assayed
testosterone
The
ment
this
E2 B treatment
cases
that the the higher
treated
experiments. for
h
concentrations
rats
two
explanation
that
the
testosterone
in the
differ
apparent
its
are
The
one
in 0 an
LH
that
levels
in the
least
FSH in
indicate
administered
0
serum reduced
trations.
on
all
That
were
gonadotropin
-I-
117
RATS
the changes
noted, LH
assay
are and
in
LH
The technical assistance of Mr. James Hayes is gratefully acknowledged. The NIH-LH-B9 was the gift of the NIH Pituitary Hormone Distribution Program. This work was supported by Grant MA-5401 from the Medical Research Council of Canada. REFERENCES Chowdhury, M., Tcholakian, B. and Steinberger, E. (1974). An unexpected effect of oestradiol-1 7S3 on luteinizing hormone and testosterone. J. Endocrinol. 60, 375-3 76. Danutra, V., Harper, M. E., Boyns, A. R., Cole, E. N., Brownsey, B. G. and Griffiths, K. (1973). The effect of certain stilboestrol analogues on plasma prolactin and testosterone in the rat. J. Endocrinol. 57, 207-215. Dc Jong, F. H., Uilenbrock, J.Th.J. and Van Der Molen, H. J. (1975). Oestradiol-17j3, testosterone and gonadotropins in oestradiol-1 7j3 treated intact adult male rats. J. Endocrinol. 65, 281-282. Moger, W. H. (1975a). Serum testosterone and luteinizing hormone concentrations in castrated imma-
ture
male
rats
treated
with
testosterone.
J. Endo-
crinol. (In Press). Moger, W. H. (1975b). Effects of testosterone metabolites on serum gonadotropin concentrations in immature male rats. Can. J. Physiol. Pharmacol. (In Press). Moger, W. H. and Armstrong, D. T. (1974). Changes in serum testosterone levels following acute LH treatment in immature and mature rats. Biol. Reprod. 11, 1-6. Niswender, G. D., Midgley, A. R., Monroe, S. E. and Reichert, L. E. (1968). Radioimmunoassay for rat luteinizing hormone with antiovine ovine LU-’ 31 1. Proc. Soc. Exp. 807-8 11. Odell, W. D., Swerdloff, R. S., Bain, and Grover, P. K. (1974). The
LU Biol.
serum Med.
and 128,
J., Wollesen, effect
of
F.
sexual
maturation on testicular response to LH stimulation of testosterone secretion in the intact rat. Endocrinology 95, 1380-1384. Steel, R. G. D. and Torrie, J. H. (1960). “Principles and Procedures of Statistics.” McGraw-Hill, New York. Verjans,
H.
Molen, oestradiol
L., H.
Dc
benzoate
in the normal 77,
636-642.
Jong,
J. and adult
F.
Eik-Nes,
H., Cooke,
B. A.,
Van
Der
K. B. (1974). Effect of on pituitary and testis function male rat. Acta Endocr. (Kbh.)
OF
14, 115-117
REPRODUCTION
Serum
(1976)
Testosterone
Response Estradiol W.
Department
to Acute
Treated H.
in
MOGER
of Physiology and Daihousie University, Nova Scotia, Canada
Halifax,
LH Treatment
Rats
Biophysics, B3H
4H7
ABSTRACT The effect of 1713-estradiol benzoate (E2 B) treatment on serum LH and FSH concentrations and the acute response of serum testosterone concentrations have been examined in intact adult male rats. E2 B treatment (100 Mg/day for 3 days) did not alter serum LH concentration or testes weights but did lower FSH levels in 1 of 2 experiments. E2 B treatment significantly decreased ventral prostate weights and serum testosterone concentrations. Acute treatment with NIH-LH-B9 (1100 Mg) resulted in significant increases in serum testosterone in both E, B treated and control rats but at all doses tested the serum testosterone concentrations obtained in E2 B treated animals were significantly less than in control animals. This work supports the hypothesis that estradiol has a direct inhibitory effect on testosterone secretion. INTRODUCTION It
has
recently
has
a
the
rat
direct
the
observation
to
et
al.,
of
in
situations
serum
The
present
gate
the
found
of
et al.
al.,
(1974)
is also
undertaken
estradiol the
not
alter
to
de
suppresonly suppressed. to
treatment
testis
NIAMDD Rat Pituitary Distribution Program. The assay procedure followed the protocol supplied with these materials with the exception that 0.1 percent gelatin replaced bovine serum albumin in the assay buffer and the incubation times employed were those of Niswender et al. (1968). Sensitivity of the assays were 4 and 8 ng for LH and FSH respectively. Statistical comparison of testes weight, ventral prostate weight, and serum gonadotropin concentrations between E2 B treated and control groups was by Student’s t test. Statistical treatment of the serum testosterone concentrations was by analysis of variance (Steel and Torrie, 1960). Significant differences have p values
g
cd.0
V
©,
#{149}
2
C N
.o
N
‘5
Sb
The male
eN
a
acute rats
dose
administration
has been related
elevation
concentrations C
-
N
.
2
h
after
of
previously
which
of reach
intraperitoneal
LH
shown
to
adult
to result
serum
in
testosterone
maximum
values
injection
(Moger
by and
‘0
6 N
E
C
o
‘5
I-
n
.
.0
x
Armstrong,
V
V
-
U
0
u
9-
present increased a dose the
dose
1974;
Odell
et
experiments LH serum testosterone dependent manner of
LH
(Fig.
2)
al.,
1974).
In
the
from 1 to 10 pg concentrations in (Fig. 1). Increasing above
10
pg
did
not
SENSITIVITY
TO
LH
IN E2 TREATED
concentration.
20-
0’ C
significantly
ments
may
volved
+
15-
treated
animals
to LH
ability
ability respond
of
the
concentrations the
least
of
experi-
in-
concenof
the
E2 B
exogenously
evidence
that
of
testoster-
inhibition
is a direct
effect
testes
to secrete
the
in
partially
to
is supporting
aspect
the changes
of testosterone
impaired
one
of
small at
inhibition
concentrations
one
at
of estradiol testoster-
one. 10’
ACKNOWLEDGMENTS
LU ‘I,
I
5
0
10
I g
30
result testes
1
NIH-LH-B9
FIG. 2. Serum testosterone after LU. Control groups, treated groups, hatched bars.
open
concentrations 2-4 bars; 17f3-estradiol
in further increases, suggesting were maximally stimulated by
doses.
The
observed LH
serum
in
control
the
different
two
experiments
lots
experiment
were
serum
ment.
of
animals
and
the
increased
and may
not
required
to
The
in
were
agreement
not with
alter
on
however,
of
the
to
the
that
these of
near
the
limit
thus
may
not
the
LH
that
is in
E2 B inhib-
by should
a
direct
be of
of small
of
concentra-
concentrations
discriminate
treat-
treatment
hypothesis
sensitivity
E2 B
E2 B
secretion.
E2B
It
pg)
amount
serum
testes.
treat(1
both
concentrations the
LH
tested
thus
by
In
depressed
minimum
that
the each
assays.
testosterone
altered
in
from
LU in
stimulate
testosterone
effect
used
separate
animals,
observation
tions
were
testosterone control
is no except
significantly dose
10 pg
difference
response
lowest serum
treated
with There
samples
assayed
testosterone
The
ment
this
E2 B treatment
cases
that the the higher
treated
experiments. for
h
concentrations
rats
two
explanation
that
the
testosterone
in the
differ
apparent
its
are
The
one
in 0 an
LH
that
levels
in the
least
FSH in
indicate
administered
0
serum reduced
trations.
on
all
That
were
gonadotropin
-I-
117
RATS
the changes
noted, LH
assay
are and
in
LH
The technical assistance of Mr. James Hayes is gratefully acknowledged. The NIH-LH-B9 was the gift of the NIH Pituitary Hormone Distribution Program. This work was supported by Grant MA-5401 from the Medical Research Council of Canada. REFERENCES Chowdhury, M., Tcholakian, B. and Steinberger, E. (1974). An unexpected effect of oestradiol-1 7S3 on luteinizing hormone and testosterone. J. Endocrinol. 60, 375-3 76. Danutra, V., Harper, M. E., Boyns, A. R., Cole, E. N., Brownsey, B. G. and Griffiths, K. (1973). The effect of certain stilboestrol analogues on plasma prolactin and testosterone in the rat. J. Endocrinol. 57, 207-215. Dc Jong, F. H., Uilenbrock, J.Th.J. and Van Der Molen, H. J. (1975). Oestradiol-17j3, testosterone and gonadotropins in oestradiol-1 7j3 treated intact adult male rats. J. Endocrinol. 65, 281-282. Moger, W. H. (1975a). Serum testosterone and luteinizing hormone concentrations in castrated imma-
ture
male
rats
treated
with
testosterone.
J. Endo-
crinol. (In Press). Moger, W. H. (1975b). Effects of testosterone metabolites on serum gonadotropin concentrations in immature male rats. Can. J. Physiol. Pharmacol. (In Press). Moger, W. H. and Armstrong, D. T. (1974). Changes in serum testosterone levels following acute LH treatment in immature and mature rats. Biol. Reprod. 11, 1-6. Niswender, G. D., Midgley, A. R., Monroe, S. E. and Reichert, L. E. (1968). Radioimmunoassay for rat luteinizing hormone with antiovine ovine LU-’ 31 1. Proc. Soc. Exp. 807-8 11. Odell, W. D., Swerdloff, R. S., Bain, and Grover, P. K. (1974). The
LU Biol.
serum Med.
and 128,
J., Wollesen, effect
of
F.
sexual
maturation on testicular response to LH stimulation of testosterone secretion in the intact rat. Endocrinology 95, 1380-1384. Steel, R. G. D. and Torrie, J. H. (1960). “Principles and Procedures of Statistics.” McGraw-Hill, New York. Verjans,
H.
Molen, oestradiol
L., H.
Dc
benzoate
in the normal 77,
636-642.
Jong,
J. and adult
F.
Eik-Nes,
H., Cooke,
B. A.,
Van
Der
K. B. (1974). Effect of on pituitary and testis function male rat. Acta Endocr. (Kbh.)
