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Effects of cortisol on uterine eosinophilia and other oestrogenic responses
Molecular
and Cellular
Endocrinology
2 (1975) 331-337.
80 North-Holland
Publ. Comp.
EFFECTS OF CORTISOL ON UTERINE EOSINOPHILIA AND OTHER OESTROGENIC RESPONSES A. TCHERNITCHIN, J. ROORYCK, X. TCHERNITCHIN J. VANDENHENDE and P. GALAND Biology
Unit, Institute
qf Interdisciplinarv
Research,
115 Boulevard
Received
24 October
The effects Whether cortisol DNA
had contents.
weight.
In contrast,
Inhibition
These data support eosinophilia
Kqvwords:
oestrogenic
inhibited
show the same higher of both
responses
our hypothesis and
oestradiol;
Two separate
cortisol
is thus
of the rat uterus
increases both uterine sensitivity
by cortisol
related
systems
in uterine eosinophilia identical
protein
and of wet
to i.p. injection
dose-response
effect of oestrogen receptor
the oestradiol,
glycogen, than
1974
were measured.
and the increase
to i.v. injection
follows
to the eosinophil
uterus:
17 December
or i.p., 12 h before
that the water-imbibition
cortisol;
receptor
responses
with oestradiol-17b,
on the oestrogen-induced
Both responses
of cortisol. uterine
on several
School,
Belgium
Accepted
i.v., simultaneously
no effects
of Brussels Medical
1000 Brussels,
1974
of cortisol
injected
Free University
de Waterloo,
curves.
is mediated
by
to be involved
in
system.
eosinophilia.
for oestrogens,
thought
independent mechanisms of oestrogen action, have been found to exist in vitro and in vivo in the uterus. These are the cytosol-nuclear receptor system and the eosinophil receptor system (Tchernitchin, 1972, 1973, 1974; Tchernitchin and Chandross, 1973). The cytosol-nuclear receptor system exists in the epithelial, stromal and muscular cells of the uterus (Tchernitchin, 1974; Tchemitchin and Chandross, 1973). This receptor system is responsible, through a two-step mechanism (Jensen et al., 1968 and 1969; Jensen and DeSombre, 1972), for the genomic response, which involves an increased transcription of mRNA. The eosinophil receptor system has been demonstrated in vitro (Txhernitchin, 1967 and 1972) and in vivo (Tchernitchin, 1974; Tchernitchin and Chandross, 1973) in the uterine eosinophils of the mature rat. Eosinophils are not present in the uterus of the immature or ovariectomized animals (Gansler, 196.5: Ry-
332
A. TcherrCtchin et al.
tomaa, 1960; Tchernitchin, 1970), but they appear as early as 5 min after an intravenous injection of oestradiol-17P to immature rats (Tchernitchin et al., 1974). The eosinophil receptor system is thought to be involved in some of the early oestrogenic responses in the uterus, such as the water imbibition, increase in vascular permeability, histamine releasing and oestrogen priming effects (Tchernitchin, 1972 and 1973). Actinomycin D has been reported to block the genomic response of oestrogens (Ui and Meuller, 1963; Hamilton, 1964; Hamilton et al., 1965; Means and Hamilton, 1966) without interfering with the early oestrogenic response (Lippe and Szego, 1965). The opposite situation has also been found to occur. Cortisol, which drastically decreases the number of eosinophils in the blood, has been found to selectively block the early oestrogenic response (see Essellier and Wagner, 1952, for a review), without interfering with the genomic response (Szego and Roberts, 1948 and 1953; Spaziani and Szego, 1959; Nicolette and Gorski, 1964). The present study was undertaken to investigate the effect of cortisol on the oestrogen-induced uterine eosinophilia and several other parameters of oestrogen stimulation, and to correlate each parameter of oestrogen stimulation, with the total number of eosinophils in the uterus.
MATERIAL
AND
METHODS
Immature female Wistar rats were injected in the jugular vein with various concentrations of oestradiol-17p in 5 y0 ethanolPsaline. The animals were sacrificed 6 h after the oestrogen administration and the uteri were excised. The right uterine horn was used for biochemical studies and the left uterine horn was fixed in neutral formalin for subsequent histological studies. The following parameters were measured for each animal: uterine wet weight, DNA (Burton, 1968), RNA (Dische, 1955), protein (Lowry et al., 1951) and glycogen (Montgomery, 1957) content, and the total number of uterine eosinophils (Tchernitchin et al., 1974). Eight to 12 animals were used for each experimental condition. The increases in uterine wet weight, RNA per unit of DNA, protein per unit of DNA and glycogen per unit of DNA were expressed as percent change over the controls. The uterine eosinophilia was expressed as the total number of eosinophils in the uterus (Tchernitchin et al., 1974).
Effects of cortisol on uterine eosinophilia
333
RESULTS In the first series of experiments, the elI’ect of a high dose of cortisol acetate on the oestrogenic response produced by various doses of oestradiol-17P was studied. Rats weighing 40 g were injected intravenously with doses of oestradiol-17P ranging from 0.001 to 30 ug per 100 g of body weight. Three groups of animals were compared: 1) animals without cortisol receiving vehicle alone, with or without additional i.p. vehicle; 2) animals intravenously injected simultaneously with the oestrogen and 2 mg of cortisol acetate (in 5% ethanol saline) per 100 g of body weight; 3) animals injected intraperitoneally with 2 mg of cortisol acetate (in 5 % ethanol - saline) per 100 g of body weight, 12 h prior to the oestrogen injection. The volume of injections was 0.5 ml in every case. As shown in fig. 1 (a, b), cortisol injected intraperitoneally produced significant decreases in both the oestrogen-induced uterine eosinophilia and the uterine wet weight response, for all doses of oestradiol-17P used. A much greater inhibition of both responses was achieved by the intravenous injection of cortisol. At all doses of oestradiol-17P tested with both routes of cortisol administration, a strong positive correlation existed between the decrease of the oestrogen-induced uterine eosinophilia and the inhibition of the uterine wet weight response. The persistence of a slight wet weight response after 0.1 ug oestradiol and 2 mg cortisol i.v. could be taken as suggesting that a small part of this response occurs independently of increased eosinophilia. In fact, whilst in those conditions, there is a low eosinophilia, lower e.g. than that observed after 0.01 ug oestradiol (a dose which does not provoke an increase in wet weight), there is, nevertheless a significant increase over the basal level of this parameter. This could suffice, in the presence of cortisol, to promote the slight wet weight response which is observed. We tend to favour this alternative possibility, since it is more compatible with dose-responses experiments (unpublished observations) showing that even the slightest wet weight response corresponded to a parallel increase in uterine eosinophilia. Cortisol did not interfere with the oestrogen-induced increases in uterine RNA and protein contents (fig. lc, d). Cortisol per se produced a moderate increase in the uterine glycogen; however, cortisol plus oestradiol-17P produced an even greater increase in the uterine glycogen, reaching the same level as in the animals treated with oestradiol-17P alone (fig. le). In the second series of experiments, the dose-effect of cortisol on the response to a constant dose of oestradiol-17P was studied. Rats weighing 60 g were injected intraperitoneally with different doses of cortisol acetate 12 h prior to
A. Tchernitchitl el al.
LY
pg
of
estrogen
per
1OOg
of
body
per
iuug of may
vmght
IO-3 10-2 IO-’ I p~9of
estrogen
ug
of estrogen
per
lOOg
per
1oOg
of
10
body
30
weight
of body
weight
b
pg 0f
Fig.
estrogen
1. Effect of cortisol
of oestrogen
stimulation.
of oestradiol-17p. of animals
)Jg OT esrroge”
on the oestrogen-induced Rats weighing
The animals
are compared:
welgnc
were sacrificed
1) animals
uterine
40 g were injected
without
eosinophilia intravenously
6 h after the oestrogen cortisol,
(0);
with 2 mg of cortisol acetate per 100 g of body weight, injection, (v), and 3) animals injected intraperitoneally
per
2) animals
IOOg
of body
and other
wclght
parameters
with different injection. injected
doses
Three groups intravenously
simultaneously with the oestrogen with 2 mg of cortisol acetate per
Effects of cortisol on uterine eosinophilia
mg of cortisol acetate per 1OOg of body weight
Fig.
2. Dose
parameters different
effect
of cortisol
on
of oestrogen
stimulation.
doses of cortisol
acetate
30 ug of oestradiol-17/3 injection.
The uterine
the uterus. are expressed
the
or vehicle.
per 100 g of body eosinophilia,
The uterine
wet weight
as a’%
of the controls.
and protein/DNA
oestrogen-induced
Rats weighing
uterine
weight
and were sacrificed
(O),
is expressed
as the total
RNA/DNA
(v)
The controls
and
with
6 h after the oestrogen number
are expressed
other with
intravenously of eosinophils
protein/DNA.
(i.e., the uterine
animals)
and
intraperitoneally
12 h later they were injected
(O),
in non-treated
eosinophilia
60 g were injected
(A),
wet weight,
in
increases
RNA/DNA
as 0% of increase.
the intravenous injection of 30 ug of oestradioL17P per 100 g of body weight. Fig. 2 shows that cortisol acetate at dosages of 0.004 or 0.04 mg per 100 g of body weight did not inhibit the oestrogen-induced uterine eosinophilia and wet weight increase. Both responses were decreased by cortisol acetate at doses of 0.4 and 2 mg per 100 g body weight. The latter dose produced the highest inhibition of both responses. The oestrogen-induced increases in RNA and protein were not decreased by any dose of cortisol used.
100 g of body weight,
12 h prior
is expressed
as the total
RNA/DNA
(c), protein/DNA
the controls. protein/DNA
number
to the oestrogen of eosinophils
injection,
(A).
in the uterus.
(d) and glycogen/DNA
The uterine
eosinophilia
(a)
The uterine
wet weight
(b),
(e) increases
are expressed
as ~5% of
The effect of the intravenous injection of cortisol on the uterine RNA/DNA, and glycogen/DNA is not shown as the results are identical to those obtained
with the intraperitoneal
injection
of cortisol
for these parameters
of oestrogen
stimulation.
336
A. Tchernitchin
et al.
DISCUSSION Oestrogens have been demonstrated to induce a migration of the eosinophils from the blood to the uterus (Gansler, 1956; Rytbmaa, 1960; Tchernitchin, 1970; Tchernitchin et al., 1974). The administration of high doses of cortisol, known to produce blood eosinopenia (Hills et al., 1948; Thorn et al., 1948; Speirs and Meyer, 1949; Quittner et al., 195 1; Essellier and Wagner, 1952; Goldlowski, 1952; Padawer and Gordon, 1952) could limit the number of eosinophils entering the uterus after oestrogen administration, resulting in the observed reduction of the oestrogen-induced uterine eosinophilia. It has been suggested that uterine eosinophils mediate some of the early oestrogenic responses in the uterus, such as the wet weight increase (Tchernitchin, 1972 and 1973). It may be expected, in this hypothesis, that wet weight increase and uterine eosinophilia will show similar sensitivity to inhibition by cortisol, whilst the latter will not necessarily interfere with the genomic response to oestrogens. In fact, our observations allow one to dissociate the oestrogen-induced increase in uterine RNA, protein and glycogen contents from the increase in uterine eosinophilia and wet weight. This is in concurrence with the hypothesis that the eosinophil receptor system for oestrogens is involved in the early oestrogenic responses, possibly through a cause-effect relationship. This possibility is reinforced by the fact that the increase in number of uterine eosinophils takes place before any change in wet weight can be detected (Tchernitchin et al., 1974). However, the alternative hypothesis is not ruled out, that both responses may depend on the same oestrogen-dependent (and cortisol-sensitive) uterine response.
ACKNOWLEDGEMENTS This work was supported by a Contract of the Ministere de la Politique Scientifique within the framework of the Association Euratom - University of Brussels - University of Pisa. Dr. A. Tchernitchin was a visiting professor at the Free University of Brussels Medical School. Present address : Department of Biology and Genetics, University of Chile Medical School, Zanartu 1042, Santiago, Chile. Dr. P. Galand is a Maitre de Recherches of the Belgian Fonds National de la Recherche Scientifique.
Effeects of cortisol
on uterine eosinophilia
337
REFERENCES Burton, K. (1968) In: Methods in Enzymology, vol. 12, Eds.: L. Grossman and K. Moldave (Academic Press, New York) p. 163. Dische, Z. (1955) In: The Nucleic Acids, vol. 1, Eds. : H. Chargaff and J. N. Davidson (Academic Press, New York) p. 301. Essellier, A. V. and Wagner, K. F. (1952) Acta Haematol. 8, 63. Gansler, H. (1956) Virchows Arch. Pathol. Anat. 329, 235. Goldlowski, Z. Z. (1952) J. Endocrinol. 8, 102. Hamilton, T. H. (1964) Proc. Natl. Acad. Sci. U.S. 5 I, 83. Hamilton, T. H., Widnell, C. C. and Tata, J. R. (1965) Biochim. Biophys. Acta 108, 168. Hills, A. G., Forsham, P. H. and Finch, C. A. (1948) Blood 3, 755. Jensen, E. V. and DeSombre, E. R. (1972) Annu. Rev. Biochem. 41, 203. Jensen, E. V., Suzuki, T., Numata, M., Smith, S. and DeSombre, E. R. (1969) Steroids 13,417. Jensen, E. V., Suzuki, T., Kawashima, T., Stumpf, W. E., Jundblut, P. W. and DeSombre, E. R. (1968) Proc. Natl. Acad. Sci. U.S. 59, 632. Lippe, B. M. and Szego, C. M. (1965) Nature 207, 272. Lowry, 0. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J. (1951) J. Biol. Chem. 193, 265. Means, A. R. and Hamilton, T. H. (1966) Proc. Natl. Acad. Sci. U.S. 56, 686. Montgomery, R. (1957) Arch. Biochem. Biophys. 67, 378. Nicolette, J. A. and Gorski, J. (1964) Endocrinology 74, 955. Padawer, J. and Gordon, A. S. (1952) Proc. Sot. Exp. Biol. Med. 80, 581. Quittner, H., Wald, N., Sussman, L. N. and Antopol, W. (1951) Blood 6, 513. Rytomaa, T. (1960) Acta Pathol. Microbial. Stand. 50 Suppl. 140. Spaziani, E. and Szego, C. M. (1959) Am. J. Physiol. 197, 355. Speirs, R. S. and Meyer, R. K. (1949) Endocrinology 45, 403. Szego, C. M. and Roberts, S. (1948) Am. J. Physiol. 152, 131. Szego, C. M. and Roberts, S. (1953) Rec. Progr. Horm. Res. 8, 419. Tchernitchin, A. (1967) Steroids 10, 661. Tchernitchin, A. (1970) Steroids 15, 799. Tchernitchin, A. (1972) Steroids 19, 575. Tchernitchin, A. (1973) J. Steroid Biochem. 4, 277. Tchernitchin, A. (1974) Eur. J. Obstet. Gynecol. Reprod. Biol. 4 (1) Suppl. (in press). Tchernitchin, A. and Chandross, R. (1973) J. Steroid Biochem. 4, 41. Tchernitchin, A., Rooryck, J., Tchernitchin, X., Vandenhende, J. and Galand, P. (1974) Nature 248, 142. Thorn, G. W., Forsham, P. H., Prunty, P. H. and Hills, A. G. (1948) J. Am. Med. Assoc. 137, 1005. Ui, H. and Mueller, G. C. (1963) Proc. Natl. Acad. Sci. U.S. 50, 256.
and Cellular
Endocrinology
2 (1975) 331-337.
80 North-Holland
Publ. Comp.
EFFECTS OF CORTISOL ON UTERINE EOSINOPHILIA AND OTHER OESTROGENIC RESPONSES A. TCHERNITCHIN, J. ROORYCK, X. TCHERNITCHIN J. VANDENHENDE and P. GALAND Biology
Unit, Institute
qf Interdisciplinarv
Research,
115 Boulevard
Received
24 October
The effects Whether cortisol DNA
had contents.
weight.
In contrast,
Inhibition
These data support eosinophilia
Kqvwords:
oestrogenic
inhibited
show the same higher of both
responses
our hypothesis and
oestradiol;
Two separate
cortisol
is thus
of the rat uterus
increases both uterine sensitivity
by cortisol
related
systems
in uterine eosinophilia identical
protein
and of wet
to i.p. injection
dose-response
effect of oestrogen receptor
the oestradiol,
glycogen, than
1974
were measured.
and the increase
to i.v. injection
follows
to the eosinophil
uterus:
17 December
or i.p., 12 h before
that the water-imbibition
cortisol;
receptor
responses
with oestradiol-17b,
on the oestrogen-induced
Both responses
of cortisol. uterine
on several
School,
Belgium
Accepted
i.v., simultaneously
no effects
of Brussels Medical
1000 Brussels,
1974
of cortisol
injected
Free University
de Waterloo,
curves.
is mediated
by
to be involved
in
system.
eosinophilia.
for oestrogens,
thought
independent mechanisms of oestrogen action, have been found to exist in vitro and in vivo in the uterus. These are the cytosol-nuclear receptor system and the eosinophil receptor system (Tchernitchin, 1972, 1973, 1974; Tchernitchin and Chandross, 1973). The cytosol-nuclear receptor system exists in the epithelial, stromal and muscular cells of the uterus (Tchernitchin, 1974; Tchemitchin and Chandross, 1973). This receptor system is responsible, through a two-step mechanism (Jensen et al., 1968 and 1969; Jensen and DeSombre, 1972), for the genomic response, which involves an increased transcription of mRNA. The eosinophil receptor system has been demonstrated in vitro (Txhernitchin, 1967 and 1972) and in vivo (Tchernitchin, 1974; Tchernitchin and Chandross, 1973) in the uterine eosinophils of the mature rat. Eosinophils are not present in the uterus of the immature or ovariectomized animals (Gansler, 196.5: Ry-
332
A. TcherrCtchin et al.
tomaa, 1960; Tchernitchin, 1970), but they appear as early as 5 min after an intravenous injection of oestradiol-17P to immature rats (Tchernitchin et al., 1974). The eosinophil receptor system is thought to be involved in some of the early oestrogenic responses in the uterus, such as the water imbibition, increase in vascular permeability, histamine releasing and oestrogen priming effects (Tchernitchin, 1972 and 1973). Actinomycin D has been reported to block the genomic response of oestrogens (Ui and Meuller, 1963; Hamilton, 1964; Hamilton et al., 1965; Means and Hamilton, 1966) without interfering with the early oestrogenic response (Lippe and Szego, 1965). The opposite situation has also been found to occur. Cortisol, which drastically decreases the number of eosinophils in the blood, has been found to selectively block the early oestrogenic response (see Essellier and Wagner, 1952, for a review), without interfering with the genomic response (Szego and Roberts, 1948 and 1953; Spaziani and Szego, 1959; Nicolette and Gorski, 1964). The present study was undertaken to investigate the effect of cortisol on the oestrogen-induced uterine eosinophilia and several other parameters of oestrogen stimulation, and to correlate each parameter of oestrogen stimulation, with the total number of eosinophils in the uterus.
MATERIAL
AND
METHODS
Immature female Wistar rats were injected in the jugular vein with various concentrations of oestradiol-17p in 5 y0 ethanolPsaline. The animals were sacrificed 6 h after the oestrogen administration and the uteri were excised. The right uterine horn was used for biochemical studies and the left uterine horn was fixed in neutral formalin for subsequent histological studies. The following parameters were measured for each animal: uterine wet weight, DNA (Burton, 1968), RNA (Dische, 1955), protein (Lowry et al., 1951) and glycogen (Montgomery, 1957) content, and the total number of uterine eosinophils (Tchernitchin et al., 1974). Eight to 12 animals were used for each experimental condition. The increases in uterine wet weight, RNA per unit of DNA, protein per unit of DNA and glycogen per unit of DNA were expressed as percent change over the controls. The uterine eosinophilia was expressed as the total number of eosinophils in the uterus (Tchernitchin et al., 1974).
Effects of cortisol on uterine eosinophilia
333
RESULTS In the first series of experiments, the elI’ect of a high dose of cortisol acetate on the oestrogenic response produced by various doses of oestradiol-17P was studied. Rats weighing 40 g were injected intravenously with doses of oestradiol-17P ranging from 0.001 to 30 ug per 100 g of body weight. Three groups of animals were compared: 1) animals without cortisol receiving vehicle alone, with or without additional i.p. vehicle; 2) animals intravenously injected simultaneously with the oestrogen and 2 mg of cortisol acetate (in 5% ethanol saline) per 100 g of body weight; 3) animals injected intraperitoneally with 2 mg of cortisol acetate (in 5 % ethanol - saline) per 100 g of body weight, 12 h prior to the oestrogen injection. The volume of injections was 0.5 ml in every case. As shown in fig. 1 (a, b), cortisol injected intraperitoneally produced significant decreases in both the oestrogen-induced uterine eosinophilia and the uterine wet weight response, for all doses of oestradiol-17P used. A much greater inhibition of both responses was achieved by the intravenous injection of cortisol. At all doses of oestradiol-17P tested with both routes of cortisol administration, a strong positive correlation existed between the decrease of the oestrogen-induced uterine eosinophilia and the inhibition of the uterine wet weight response. The persistence of a slight wet weight response after 0.1 ug oestradiol and 2 mg cortisol i.v. could be taken as suggesting that a small part of this response occurs independently of increased eosinophilia. In fact, whilst in those conditions, there is a low eosinophilia, lower e.g. than that observed after 0.01 ug oestradiol (a dose which does not provoke an increase in wet weight), there is, nevertheless a significant increase over the basal level of this parameter. This could suffice, in the presence of cortisol, to promote the slight wet weight response which is observed. We tend to favour this alternative possibility, since it is more compatible with dose-responses experiments (unpublished observations) showing that even the slightest wet weight response corresponded to a parallel increase in uterine eosinophilia. Cortisol did not interfere with the oestrogen-induced increases in uterine RNA and protein contents (fig. lc, d). Cortisol per se produced a moderate increase in the uterine glycogen; however, cortisol plus oestradiol-17P produced an even greater increase in the uterine glycogen, reaching the same level as in the animals treated with oestradiol-17P alone (fig. le). In the second series of experiments, the dose-effect of cortisol on the response to a constant dose of oestradiol-17P was studied. Rats weighing 60 g were injected intraperitoneally with different doses of cortisol acetate 12 h prior to
A. Tchernitchitl el al.
LY
pg
of
estrogen
per
1OOg
of
body
per
iuug of may
vmght
IO-3 10-2 IO-’ I p~9of
estrogen
ug
of estrogen
per
lOOg
per
1oOg
of
10
body
30
weight
of body
weight
b
pg 0f
Fig.
estrogen
1. Effect of cortisol
of oestrogen
stimulation.
of oestradiol-17p. of animals
)Jg OT esrroge”
on the oestrogen-induced Rats weighing
The animals
are compared:
welgnc
were sacrificed
1) animals
uterine
40 g were injected
without
eosinophilia intravenously
6 h after the oestrogen cortisol,
(0);
with 2 mg of cortisol acetate per 100 g of body weight, injection, (v), and 3) animals injected intraperitoneally
per
2) animals
IOOg
of body
and other
wclght
parameters
with different injection. injected
doses
Three groups intravenously
simultaneously with the oestrogen with 2 mg of cortisol acetate per
Effects of cortisol on uterine eosinophilia
mg of cortisol acetate per 1OOg of body weight
Fig.
2. Dose
parameters different
effect
of cortisol
on
of oestrogen
stimulation.
doses of cortisol
acetate
30 ug of oestradiol-17/3 injection.
The uterine
the uterus. are expressed
the
or vehicle.
per 100 g of body eosinophilia,
The uterine
wet weight
as a’%
of the controls.
and protein/DNA
oestrogen-induced
Rats weighing
uterine
weight
and were sacrificed
(O),
is expressed
as the total
RNA/DNA
(v)
The controls
and
with
6 h after the oestrogen number
are expressed
other with
intravenously of eosinophils
protein/DNA.
(i.e., the uterine
animals)
and
intraperitoneally
12 h later they were injected
(O),
in non-treated
eosinophilia
60 g were injected
(A),
wet weight,
in
increases
RNA/DNA
as 0% of increase.
the intravenous injection of 30 ug of oestradioL17P per 100 g of body weight. Fig. 2 shows that cortisol acetate at dosages of 0.004 or 0.04 mg per 100 g of body weight did not inhibit the oestrogen-induced uterine eosinophilia and wet weight increase. Both responses were decreased by cortisol acetate at doses of 0.4 and 2 mg per 100 g body weight. The latter dose produced the highest inhibition of both responses. The oestrogen-induced increases in RNA and protein were not decreased by any dose of cortisol used.
100 g of body weight,
12 h prior
is expressed
as the total
RNA/DNA
(c), protein/DNA
the controls. protein/DNA
number
to the oestrogen of eosinophils
injection,
(A).
in the uterus.
(d) and glycogen/DNA
The uterine
eosinophilia
(a)
The uterine
wet weight
(b),
(e) increases
are expressed
as ~5% of
The effect of the intravenous injection of cortisol on the uterine RNA/DNA, and glycogen/DNA is not shown as the results are identical to those obtained
with the intraperitoneal
injection
of cortisol
for these parameters
of oestrogen
stimulation.
336
A. Tchernitchin
et al.
DISCUSSION Oestrogens have been demonstrated to induce a migration of the eosinophils from the blood to the uterus (Gansler, 1956; Rytbmaa, 1960; Tchernitchin, 1970; Tchernitchin et al., 1974). The administration of high doses of cortisol, known to produce blood eosinopenia (Hills et al., 1948; Thorn et al., 1948; Speirs and Meyer, 1949; Quittner et al., 195 1; Essellier and Wagner, 1952; Goldlowski, 1952; Padawer and Gordon, 1952) could limit the number of eosinophils entering the uterus after oestrogen administration, resulting in the observed reduction of the oestrogen-induced uterine eosinophilia. It has been suggested that uterine eosinophils mediate some of the early oestrogenic responses in the uterus, such as the wet weight increase (Tchernitchin, 1972 and 1973). It may be expected, in this hypothesis, that wet weight increase and uterine eosinophilia will show similar sensitivity to inhibition by cortisol, whilst the latter will not necessarily interfere with the genomic response to oestrogens. In fact, our observations allow one to dissociate the oestrogen-induced increase in uterine RNA, protein and glycogen contents from the increase in uterine eosinophilia and wet weight. This is in concurrence with the hypothesis that the eosinophil receptor system for oestrogens is involved in the early oestrogenic responses, possibly through a cause-effect relationship. This possibility is reinforced by the fact that the increase in number of uterine eosinophils takes place before any change in wet weight can be detected (Tchernitchin et al., 1974). However, the alternative hypothesis is not ruled out, that both responses may depend on the same oestrogen-dependent (and cortisol-sensitive) uterine response.
ACKNOWLEDGEMENTS This work was supported by a Contract of the Ministere de la Politique Scientifique within the framework of the Association Euratom - University of Brussels - University of Pisa. Dr. A. Tchernitchin was a visiting professor at the Free University of Brussels Medical School. Present address : Department of Biology and Genetics, University of Chile Medical School, Zanartu 1042, Santiago, Chile. Dr. P. Galand is a Maitre de Recherches of the Belgian Fonds National de la Recherche Scientifique.
Effeects of cortisol
on uterine eosinophilia
337
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