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Lipid Peroxidation and Free Radical Scavengers in Thyroid Dysfunction in the Rat: A
Possible Mechanism of Injury to Heart and Skeletal Muscle in Hyperthyroidism*

Article  in  Endocrinology · January 1988

DOI: 10.1210/endo-121-6-2112 · Source: PubMed

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Endocrinology
Copyright© 1987 by The Endocrine Society
Lipid Peroxidation and Free Radical Scavengers in
Thyroid Dysfunction in the Rat: A Possible Mechanism
of Injury to Heart and Skeletal Muscle in
Hyperthyroidism*
KOHTARO ASAYAMA, KAZUSHIGE DOBASHI, HIDEMASA HAYASHIBE,
YOSHINORI MEGATA, AND KIYOHIKO KATO
Department of Pediatrics, Yamanashi Medical College, Yamanashi, Japan 409-38
ABSTRACT. This study was designed to determine if peroxi-
dation of biomembrane lipid and the protective system can be
modified by the change in oxidative metabolism induced by
thyroid dysfunction. The free radical scavengers (i.e. cuprozinc
cytosolic and mangano mitochondrial superoxide dismutases,
glutathione peroxidase, and catalase), mitochondrial oxidative
marker enzymes (cytochrome c oxidase and fumarase), and lipid
peroxide were measured in liver, heart, soleus (slow oxidative),
and extensor digitorum longus (fast glycolytic) muscles. Rats
were rendered hyper- or hypothyroid for 4 weeks and then killed.
Superoxide dismutases were detected by specific RIAs: catalase
by polarography, and lipid peroxide by fluorimetry.
Hypothyroid rats failed to grow, while hyperthyroid rats had
hypertrophied hearts but no growth failure. An increase in lipid
peroxide was observed in the soleus and heart muscles of hyper-
thyroid rats. This was accompanied by an increase in mitochon-
I N AEROBIC cells, active oxygen species, e.g. super-
oxide and hydrogen peroxide, are generated as by-
products of oxidative metabolism in mitochondria. These
species are toxic to biomembrane and eventually lead to
peroxidation of lipid unless they are removed by free
radical-scavenging enzymes, which comprise superoxide
dismutase (SOD), glutathione peroxidase, and catalase.
There are two forms of SOD. One contains copper and
zinc (CuZnSOD) and is found predominantly in cytosol,
and the other contains manganese (MnSOD) and is
found predominantly in mitochondria (1). Glutathione
peroxidase and catalase catalyze the reduction of hydro-
gen peroxide; the former also catalyzes the reduction of
certain lipid peroxides. We previously demonstrated the
differential regulation of free radical-scavenging enzymes
Received April 3, 1987.
Address all correspondence and requests for reprints to: Kohtaro
Asayama, M.D., Department of Pediatrics, Yamanashi Medical College,
1110 Shimokato, Tamaho, Nakakoma, Yamanashi Japan 409-38.
* This work was supported in part by Grant-in-Aid 61770650 from
the Ministry of Education (Japan) and a grant-in-aid from the Naito
Foundation.
2112
Vol. 121, No. 6
Printed in U.S.A.
drial superoxide dismutase and oxidative markers. No such
change was observed in either fast glycolytic muscle or liver.
Glutathione peroxidase decreased in all tissues of hyperthyroid
rats, and there was a parallel decrease in catalase in most tissues.
On the other hand, hypothyroidism induced a reduction in
oxidative markers and mitochondrial superoxide dismutase in
heart and skeletal muscles, but only a marginal change in lipid
peroxidation. The cytosolic superoxide dismutase did not change
in relation to either oxidative metabolism or lipid peroxidation.
These results suggest that the enhanced oxidative metabolism
and decreased glutathione peroxidase in hyperthyroidism result
in an increase in lipid peroxidation and, in slow oxidative and
heart muscle, possible organ damage. No adverse reaction me-
diated by active oxygen species was found in hypothyroid rat
tissues. (Endocrinology 121: 2112-2118, 1987)
in tissues (2) in response to changes in oxidative metab-
olism (3, 4).
It is well established that thyroid hormone accelerates
the basal metabolic rate and, more specifically, oxidative
metabolism, as evidenced by the induction of certain
mitochondrial enzymes in target tissues (5-7). It has also
been reported that excessive thyroid hormone may in-
duce tissue injury. Thyrotoxic myopathy (8) and myo-
cardial insufficiency (9) are well known examples of
tissue damage due to the direct action of thyroid hormone
on target tissues. The pathophysiological basis of these
abnormalities is not clear. It is possible that activation
of mitochondrial respiration by thyroid hormone results
in oxidative tissue injury secondary to increased produc-
tion of active oxygen species.
The activities of SOD, detected via indirect assay, and
catalase in skeletal muscle of hyperthyroid and euthyroid
rats have been reported (10). To our knowledge, the
regulation of free radical-scavenging enzymes in relation
to thyroid status has not been studied systematically.
We attempted, therefore, to determine if changes in
 RADICAL SCAVENGERS AND THYROID STATUS
mitochondrial oxidative metabolism due to thyroid dys-
function lead to selective modification of free radical
scavenging enzymes in various tissues in the rat. We also
measured malondialdehyde, an index of lipid peroxida-
tion, to monitor potential damage to biomembrane lipid
in tissues.
Materials and Methods
Animal treatment
Twenty-one 5-week-old male Sprague-Dawley rats (Shi-
zuoka Laboratory Animal Center, Shizuoka, Japan) were given
free access to a standard chow and water. The animals were
divided into three weight-matched groups. Control rats (euthy-
roid, group I) were given tap water. The remaining rats were
rendered either hyperthyroid (group II) or hypothyroid (group
III) by the administration of 0.0012% L-T4 or 0.05% propyl-
thiouracil (PTU), respectively, to their drinking water over a
4-week period, as described by Ladenson et al. (11). The mean
initial body weights for groups I, II, and III were 139, 138, and
136 g, respectively. The rats were killed under pentobarbital
anesthesia (50 mg/kg), and their sera were frozen and stored
until assayed for T 3 and T4. Specimens of liver, heart, bilateral
soleus (slow oxidative), and extensor digitorum longus (EDL;
fast glycolytic) muscles were obtained. The tissues were rinsed
with PBS, blotted with gauze, and kept frozen at -80 C. Each
skeletal muscle was treated separately. The right hindlimb
muscles were used for enzyme assays, and the left for determi-
nation of lipid peroxide.
Homogenate preparation
For enzyme assays the tissues were homogenized with 20
times their volume of 10 mM potassium phosphate buffer con-
taining 0.01% digitonin (pH 7.4) in a Potter-Elvehjem homog-
enizer, and then sonicated on ice for 30 sec (15 sec, twice). The
sonicate was centrifuged at 13,000 x g for 5 min, and the
supernatant was stored frozen in aliquots at —80 C until as-
sayed. For lipid peroxide determination, tissue samples were
homogenized with 10 times their volume of 1.15% potassium
chloride and centrifuged at 3,000 x g for 10 min, and the
supernatant was obtained.
Biochemical analyses
The RIAs for rat CuZnSOD and MnSOD have been de-
scribed previously (12). The activities of cytochrome c oxidase,
fumarase, and glutathione peroxidase were assayed by methods
described previously (4). Catalase activity was assayed polaro-
graphically with a type PO-100A oxygen electrode (Yanagimoto
Mfg. Co., Ltd., Kyoto, Japan). The initial rate of O2 generation
was measured in a 0.1-M sodium phosphate buffer (pH 7.0)
saturated with ambient oxygen at 25 C, with 7 mM H2O2 as a
substrate. The activity was calculated assuming the concentra-
tion of O2 in air-saturated water at 25 C at a barometric pressure
of 760 mm Hg to be 0.252 mM. The tissue concentration of
lipid peroxide was estimated from fluorimetric measurement of
thiobarbituric acid (TBA)-reactive substance, as described by
2113
Yagi et al. (13). Protein was measured by the technique of
Lowry et al. (14). Serum T:! and T4 concentrations were deter-
mined with commercial RIA kits.
Statistics
The data are presented as the mean ± SE. Statistical signif-
icance was determined by the method of least significant dif-
ference, calculated after one-way analysis of variance.
Results
Effect of thyroid status on body and tissue growth
Serum T 3 levels in the control (group I), T4-treated
(group II), and PTU-treated (group III) rats were 54 ±
4, 304 ± 14, and 27 ± 2 ng/dl, respectively, and were
significantly different from each other (group II > I and
III, P > 0.001; I > III, P > 0.05). Serum T4 levels in the
three groups were: group I, 3.6 ± 0.2; group II, 12.1 ± 0.5;
and group III, less than 0.1 Aig/dl. These values were
similar to those reported by Ladenson et al. (11), con-
firming that hyper- and hypothyroidism were attained
in these rats. The final body weights were: group I, 340
± 8; group II, 329 ± 10; and group III, 231 ± 5 g (group
III < I and II, P < 0.001). Table 1 lists the organ weights
and organ to body weight ratios for skeletal muscles,
heart, and liver. The heart was hypertrophied in T4-
treated rats, according to both the net weight and the
weight relative to body weight (P < 0.001). On the other
hand, both the net and relative weights of other organs
in the T4-treated rats were similar to those in the con-
trols, with the exception of a marginal difference in the
right soleus (P < 0.05). In PTU-treated rats, the net
weight of all organs studied was low (P < 0.001); the
relative weight of the soleus was high (P < 0.01), while
those of the heart (P < 0.01) and liver (P < 0.02) were
low. The relative weight of EDL muscles was normal.
Activity of mitochondrial marker enzymes
Hyperthyroidism markedly increased (P < 0.001) and
hypothyroidism decreased both cytochrome c oxidase and
fumarase in soleus (Table 2 and Fig. 1). Similarly, in
heart, fumarase increased in hyperthyroidism and cyto-
chrome c oxidase decreased in hypothyroidism. On the
other hand, in EDL these enzymes did not increase in
hyperthyroidism, whereas both decreased in hypothy-
roidism. Neither enzyme was altered in liver.
Tissue concentration of superoxide dismutases
The effect of thyroid status on the tissue concentration
of MnSOD is illustrated in Fig. 2. Hyperthyroidism
increased and hypothyroidism decreased MnSOD in both
soleus and heart. On the other hand, MnSOD levels in
EDL and liver in both T4- and PTU-treated rats were
2114 RADICAL SCAVENGERS AND THYROID STATUS Endo • 1987
Vol 121-No 6

TABLE 1. Organ weight and organ to body weight ratio

Soleus EDL
T * r\

R L R L
mg mg mg mg g g

Organ wt
I. Control 135 ± 3" 134 ± 4 172 ± 3 171 ± 3 1.17 ± 0.05" 14.0 ± 0.7
II. T4-treated 122 ± 4C 124 ± 4C 158 ± 6d 158 ± 6d 1.63 ± 0.06rf 13.4 ± 0.5d
III. PTU-treated 109 ± 5C 110 ± 4e 119 ± 5 e 117 ± V 0.70 ± 0.02e 8.5 ± 0.317
Mg/g Mg/g Mg/g Mg/g mg/g mg/g
Organ/BW ratio
I. Control 389 ± 9 394 ± 7 506 ± 13 506 ± 17 3.43 ± 0.106 41.2 ± 1.3
II. T4-treated 372 ± 18d 376 ± 22d 483 ± 19 483 ± 22 4.97 ± 0.10d 42.3 ± 1.2'
III. PTU-treated 474 ± 16* 475 ± 15g 515 ± 18 509 ± 17 3.03 ± 0.07* 36.6 ± 1.1*
Data are the mean ± SE of seven observations for each group.
a
P < 0.05,1 us. II.
6
P < 0.001,1 vs. II.
c
P < 0.05, II us. III.
"P < 0.001, II us. III.
e
P < 0.001,1 vs. III.
f
P< 0.01, II vs. III.
" P < 0.01,1 vs. III.
h
P < 0.02, I vs. III.

TABLE 2. Activities of cytochrome c oxidase and catalase in tissues

Cytochrome c oxidase Catalase

Soleus EDL Heart Liver Soleus EDL Heart Liver
fc
I. Control 79.1 ± 7.4" 75.1 ± 2.1" 144 ± 4 50.9 ± 8.9 362 ± 25 74.9 ± 5.2 1.83 ± 0.16 27.3 ± 0.9"
II. T4-treated 118.8 ± 8.9C 51.9 ± 2.8d 134 ± 3 e 46.9 ± 4.7 300 ± 29 C 67.3 ± 5.4 d 1.05 ± 0.08c 15.1 ± 1.1°
III. PTU-treated 53.8 ± 3.5' 6.2 ± 4.2g 110 ± 6 " 52.9 ± 5.3 671 ± nh 89.6 ± 10. 1 2.10 ± 0.22 21.5 ± 0.9*
Data are the mean ± SE of seven observations for each group. Values are in unit (sec ') per g protein for cytochrome c oxidase, and in nanomoles
of O2 generated per min/mg protein in soleus and EDL and micromoles of O2 generated per min/mg protein in heart and liver for catalase.
" P < 0.001,1 vs. II.
* P < 0.01,1 vs. II.
c
P < 0.001, II vs. III.
d
P < 0 . 0 5 , II us. III.
0
P < 0.01, II us. III.
' P < 0 . 0 2 , 1 vs. III.
* P < 0.05,1 vs. III.
h
P < 0.001,1 vs. III.

similar to those in the controls. In contrast, CuZnSOD
levels in skeletal muscles did not change in relation to
thyroid status, and in heart it was even higher in hypo-
thyroid than in control rats (P < 0.05; Fig. 3). In liver,
CuZnSOD tended to decrease in both T4-treated (P <
0.001) and PTU-treated rats (P < 0.02).
Activities of glutathione peroxidase and catalase
The activity of glutathione peroxidase in EDL was
approximately l/10th that in soleus and heart and 1/
20th that in liver. Enzyme activity decreased in all tissues
in T4-treated rats, while that in EDL and heart increased
significantly in PTU-treated rats (Fig. 4). Catalase activ-
ity in tissues is summarized in Table 2. The enzyme
activity was very high in liver, low in heart, and ex-
tremely low in skeletal muscles. Hyperthyroidism signif-
icantly decreased the enzyme activity in heart and liver,
whereas hypothyroidism increased it in soleus and de-
creased it in liver.
Malondialdehyde level in tissue homogenate
The malondialdehyde level increased to 200% in soleus
and to 134% in heart in the T4-treated rats compared
with control values (P < 0.001; Fig. 5). There was no
change in liver and only a slight decrease (P < 0.01) in
EDL in the PTU-treated rats.
Discussion
Hyperthyroidism enhanced mitochondrial oxidative
metabolism in slow oxidative muscle (soleus) and heart.
 RADICAL SCAVENGERS AND THYROID STATUS 2115

1.5- 5.0-
I
4.0-

1.0-
3.0-
TO o> a i
o s
i
if =0.5H
(/) a. 2.0-
C E
N \
1.0-
a a

Soleus EDL Heart Liver

FIG. 1. Fumarase activity in various tissues in rats. Data are the means
of seven observations. The brackets indicate SE. D, Controls (group I);
• , T4-treated rats (group II); M, PTU-treated rats (group III). Statistical
significance is as follows: group I vs. II: a, P < 0.001; group II vs. Ill: b,
P < 0.001; c, P < 0.02; group I us. Ill: d, P < 0.001; e, P < 0.005.
Soleus EDL Heart Liver
FIG. 3. Immunoreactive CuZnSOD concentrations in various tissues
in rats. Data are the mean ± SE (n = 7). D, Controls; • , T4-treated; M,
PTU-treated. Statistical significance: group I vs. II: a, P< 0.001; group
II vs. Ill: b, P < 0.02; group I vs. Ill: c, P < 0.02; d, P < 0.05.

0.1-

iI
a
•2.0- X 1.0-

1
ro 0.5-
°i
00 a X
c
b
O) o
prot

(D
CL 0.05-
1.0- d
Q) O)
{— E 0.5-
o\
c "E
4->

Soleus EDL Heart Liver 0

FIG. 2. Immunoreactive MnSOD concentrations in various tissues in
rats. Data are the mean ± SE (n = 7). D, Controls; • , T4-treated; H,
PTU-treated. Statistical significance: group I us. II: a, P < 0.001; b, P
< 0.01; group II vs. Ill: c, P < 0.001; d, P < 0.01; e, P < 0.02; group I
vs. Ill: f, P < 0.001; g, P < 0.02. Groups I-III are defined in Fig. 1.
This was associated with increases in MnSOD and lipid
peroxidation in these tissues. Such changes were not
observed in fast glycolytic muscle (EDL) or liver of
hyperthyroid rats. Hypothyroidism suppressed oxidative
metabolism in soleus, EDL, and heart, but not in liver,
and decreased MnSOD only in soleus and heart, but not
in EDL or liver. On the other hand, glutathione peroxi-
dase decreased in hyperthyroidism and was either normal
or high in hypothyroidism in all tissues studied. Simi-
larly, catalase tended to be low in hyperthyroidism and
high in hypothyroidism in most of the tissues.
The tissue level of MnSOD corresponded with that of
fumarase and, less closely, with that of cytochrome c
Soleus EDL Heart Liver
FIG. 4. Glutathione peroxidase activity in various tissues in rats. Data
are the mean ± SE (n = 7). D, Controls; • , T4-treated; M, PTU-treated.
Statistical significance: group I vs. II: a, P < 0.001; b, P < 0.005; c, P
< 0.05; group II vs. Ill: d, P < 0.001; e, P < 0.01; group I vs. Ill: f, P <
0.001; g, P < 0.01.
oxidase. This finding is similar to our previous observa-
tion in denervated rat skeletal muscle (4). Similarly, the
changes in tissue levels of malondialdehyde mimicked
those in levels of the enzymes localized in mitochondrial
matrix (i.e. MnSOD and fumarase). This implies that
the elevated malondialdehyde level in the homogenate of
hyperthyroid soleus and heart was mainly due to the
enhanced lipid peroxidation in mitochondrial membrane.
Further, it is known that ubisemiquinone in complex III
of the respiratory chain is the major electron donor for
cyanide-sensitive superoxide formation, and that free
radical production in mitochondria is closely related to
2116 RADICAL SCAVENGERS AND THYROID STATUS
2.0-
0.5-
E protein), nonetheless, declines. Further, thyroid hormone
\ 1.0-
QQ
I-
Soleus EDL Heart Liver
FIG. 5. The concentration of TBA-reactive substance (malondialde-
hyde) in various tissues in rats. Data are the mean ± SE (n = 7). D,
Controls; • , T4-treated; H, PTU-treated. Statistical significance: group
I vs. II: a, P < 0.001; group II vs. Ill: b, P < 0.001; c, P < 0.01; group I
vs. Ill: d, P < 0.01.
oxidative metabolism (15). These data suggest that reg-
ulation of the MnSOD concentration is related to oxi-
dative metabolism and, in turn, to mitochondrial free
radical production, which leads to membrane lipid per-
oxidation.
In contrast, CuZnSOD, which was unchanged in both
heart and skeletal muscle, decreased in liver in response
to thyroid dysfunction. However, no alteration in oxi-
dative metabolic activity was observed in liver, indicating
that the regulation of CuZnSOD was independent of
oxidative metabolism and was different from that of
MnSOD. These findings suggest that the two isoenzymes
scavenge superoxide from different subcellular sites of
generation, one from cytosol and the other from mito-
chondria. This conclusion supports previous experimen-
tal data obtained with specific RIAs for SODs (4-6).
The parallel decreases in glutathione peroxidase and
catalase in all tissues in hyperthyroid animals suggest
that these are due to a more general effect of thyroid
hormone than that on oxidative metabolism. Thyroid
hormone is known not only to promote the synthesis of
certain specific proteins, such as mitochondrial enzymes,
but also to enhance the protein degradation (16,17). The
latter has been reported to occur via activation of lyso-
somal enzymes in both skeletal muscle and liver, but not
in heart (18). It is known that physiological doses of
thyroid hormone are growth promoting to liver and skel-
etal muscle (19). Therefore, there must have been a
catabolic phase in the skeletal muscle and liver of the
hyperthyroid rats in this study, whose sizes were com-
parable to those of the controls. Assuming that neither
glutathione peroxidase nor catalase synthesis is pro-
moted by thyroid hormone, the increased degradation
might explain the low enzyme concentrations in the
Endo • 1987
Vol 121* No 6
hyperthyroid rats. On the other hand, hyperthyroid car-
diac muscle, in which lysosomal enzyme is not activated,
hypertrophies because of the increase in the synthesis of
myosin, a major structural protein. Even though the total
tissue content of both enzymes remains the same, as was
the case in this study, the specific activity (per mg
is known to affect the fiber composition of both skeletal
and heart muscles (20, 21). As was demonstrated in this
study, type I skeletal muscle is rich in both enzymes
relative to type II muscle. The conversion of fiber types
associated with hyperthyroidism (i.e. from type I to type
II) may contribute to the decrease in these enzymes in
soleus muscle.
Numerous publications have described the structural
(22), biochemical (8), and electrodynamic (23) features
of thyrotoxic myopathy in rodents. It has been shown
that thyroid hormone has a more profound effect on
slow-twitch muscle than on fast-twitch muscle (24), as
was the case in the study reported here. It has been
postulated that in exercise-induced myopathy, exhaus-
tive exercise increases mitochondrial respiration to meet
the increased energy demand, resulting in enhanced free
radical production and lipid peroxidation, which, in turn,
induce myopathic change (25). Higuchi et al. (10) spec-
ulated that an increase in MnSOD in soleus is not
effective as a protective adaptation to either exercise-
induced or thyrotoxic myopathy, based on the fact that
the increase in oxidative marker enzymes is greater than
that in MnSOD. In the rats we studied, MnSOD was
increased more than oxidative marker enzymes, whereas
there was no protection against the accelerated lipid
peroxidation. Glutathione peroxidase is the principal
scavenger of H2O2 unless the concentration of H2O2 is
high, as is occasionally the case in liver (26). Thus, a
decrease in this enzyme may contribute to oxidative
injury in skeletal muscle.
Thyrotoxic cardiomyopathy is not as well defined as
other myopathies. The existence of reversible cardio-
myopathy is suggested by the fact that left ventricular
function is abnormal in clinical hyperthyroidism (27, 28).
Electron microscopic studies have revealed localized
areas of vacuolization and disorientation of mitochon-
drial cristae in the hearts of hyperthyroid rats (29). In
our study, the increase in MnSOD failed to protect
against enhanced lipid peroxidation in both hyperthyroid
heart and soleus, suggesting that the decrease in gluta-
thione peroxidase has pathophysiological consequences.
In fact, the importance of this enzyme in the mainte-
nance of normal cardiac function was dramatically illus-
trated by a study of Keshan disease, a cardiomyopathy
resulting from dietary selenium deficiency (30) in which
the activity of the selenoenzyme glutathione peroxidase
is markedly decreased. In another investigation, cardio-
 RADICAL SCAVENGERS AND THYROID STATUS
myopathy due to cadmium intoxication in rats was ac-
companied by a decrease in the activity of glutathione 8.
peroxidase and a rise in the malondialdehyde level in the
heart (31). Although our hyperthyroid rats exhibited 9.
neither growth failure nor signs of cardiac failure, they
did undergo biochemical changes that predisposed them 10.
to cardiac dysfunction.
In contrast to the other tissues, the livers of our rats 11.
did not respond to thyroid dysfunction with respect to
oxidative metabolism. This result is inconsistent with
12.
previous demonstrations of a significant escalation of
oxidative metabolism in hyperthyroid liver (6, 32). The
dosage of T4 that we administered was far greater than 13.
the physiological dose used by DeMartino and Goldberg
(18), and the serum T 3 and T4 levels were in the thyro-
toxic range. One difference between our study and those 14.
in which such liver changes were observed is that the 15.
other regimens included T 3 and ours only T4. It has been
shown that thyrotoxic liver damage is not due to a direct
16.
action of the hormone and occurs only in severe hyper-
thyroidism (33). A greater or more rapid increase in
serum T 3 than occurred in our study might be required
17.
to effect such a result.
In addition to suppressing growth, hypothyroidism
decreased oxidative marker enzymes in skeletal muscle 18.
and heart. This result is consistent with the observations
by Johnson and Turnbull (7) in rat skeletal muscle and 19.
is probably related to the hypometabolic state induced
by hypothyroidism. Further, hypothyroidism induced 20.
changes in free radical-scavenging enzymes of heart and
skeletal muscles opposite those observed in hyperthy-
21.
roidism. However, this was accompanied by only a mar-
ginal change in the tissue levels of malondialdehyde. It
appears that active oxygen species are not involved in 22.
the organ dysfunction associated with hypothyroidism.
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Eleventh International Congress on Animal Reproduction and Artificial

Insemination
Eleventh International Congress on Animal Reproduction and Artificial Insemination will be held at
University College Dublin from June 26-30,1988. There will be three Plenary sessions and twelve symposia
on several aspects of mammalian reproduction. In addition, there are fifteen workshops planned. Short
communications, to be presented as posters, on any aspect of reproduction are welcome.
Please contact:
Dr. Maurice Boland
Congress Secretary
University College Dublin
Lyons Estate
Newcastle Co.
Dublin, Ireland
Tel. 01-288385
Telex 32693 (UCD) El
Early registration up to January 31, 1988.