Testosterone
potentiation of the effectiveness of ACTH on the
induction of the strech-yawning syndrome in male
Guinea Pigs
J Rodriguez-Sierra, E Terasawa, D Goldfoot,
D De Wield
Wisconsin regional primate
research center, University of
Wisconsin
Several cases of mutually potentiating
behavioral effects of peptide and steroid
hormones have been suggested in recent years.
These include possible interactions of
luteinizing hormone-releasing hormone (LHRH) and
estradiol for the display of lordosis, of ACTH
and testosterone for facilitation of certain
measures of sexual arousal, and of interactions
between several pituitary hormones and adrenal
steroids for phenomena related to agonism and to
avoidance learning. The underlying neural
processes through which these potentiating
effects act remain to be discovered.
The display of a combined stretching and
yawning pattern (SYS) has been demonstrated
previously in many laboratory species following
intracranial administration of ACTH.
Gispen, Wiegant, Greven, and DeWied, (1975)
demonstrated that the display of SYS in response
to ACTH was independent of the adrenals, gonads,
and pituitary gland, and therefore probably
represents a direct central effect. It has also
been shown, however, that androgens (TP and
dihydrotestosterone propionate, DHTP) elicited
yawning in several species. However, in cases of
androgen potentiated yawning, stretching
was not usually seen. In the present study, the
separate and combined actions of ACTH and
testosterone propionate (TP) were examined for
their influences on a simple stretching and
yawning pattern (SYS) in the castrated male
guinea pig. Attempts were made to distinguish
-yawns from "stretch-yawns"and from "stretches",
analyzing each of these three patterns as
separate behaviors. In addition, other patterns
of behavior reported to be elicited following
intracranial treatment with ACTH in other
species, e.g., self-grooming, penile erections,
and wet-dog shaking were also recorded when they
occurred. The purpose of the study was therefore
to determine similarities and differences of
response of the guinea pig to intracranial ACTH
in comparison to those reported for other
species, and to determine whether testosterone
treatment interacted in these processes.
[...]
Results :
Experiment 1 revealed that intracranial
administration of ACTH into the male guinea pig
resulted in a dose-related increase in frequency
of SYS. The lowest dosage of ACTH used (0.08
jug) was not different from the saline vehicle
condition, but all other doses showed clear
effects, with 0.4 µg being intermediate in
effect and 2.0 µg giving the maximal
response. The highest dose employed (8.0
µg) did not further enhance the response,
and was in fact (nonsignificantly) less
effective than the 2.0 µg treatment.
The simultaneous administration of TP in
this experiment restilied in an augmented mean
SYS at every dosage level employed, although the
overall effect of TP + ACTI failed to be
significantly different from the oil + ACTH
treatment. In both treatment conditions, and at
each dose level, no significant augmentation of
grooming, shaking, scratching, or penile
erections was found.
Experiment 2 analyzed the question of
TP-ACTH interactions, and demonstrated that TP
treatment itself, without the concomitant
administration of ACTH only minimally influenced
stretch-vawning patterns. Figure 3 shows that a
mean increase in stretch-yawns occurred, but
that this difference was not statistically
significant. TP did induce a clear augmentation
of yawns not accompanied by stretches however,
it had no measurable influence on the frequency
of stretches.
ACTH augmented stretch-yawns when given by
itself, but had no influence on yawns or on
stretches when these behaviors were displayed
singly. The behavior patterns obtained with ACTH
were therefore distinct from those displayed in
response to the TP treatment: ACTH stimulated
stretch-yawns, and TP stimulated yawns. Neither
hormone stimulated stretching by itself.
When ACTH and TP were given simultaneously,
no augmentation of stretching by itself was
seen, and no augmentation of yawning beyond that
obtained with TP-alone occurred. Stretch-yawning
was considerably potentiated with the combined
treatment, however, and was significantly more
frequently expressed than in the TP-alone or
ACTH-alone conditions. However, as in experiment
1, no significant changes in the frequencies of
any other behavior measured in this study were
found following treatment with ACTH with TP, or
with the combined steroid and peptide
treatment.
Discussion :
The present experiment clearly showed that
ACTH is effective in inducing the SYS in male
guinea pig as it does in a number of other
mammalian species. Sex steroids are not
necessary for the action of peptide hormones;
ACTH induced SYS in orchidectomized males and
ovariectomized females. However, testosterone
potentiates the effectiveness of ACTH. This
is in disagreement with a report by Bertolini
and Baraldi (1976) who found no apparent
differences in the incidence of SYS in
androgen-injected rats compared to castrated
animals after ACTH administration. This
discrepancy might be due to either species
differences or differences in their protocol
from our experimental treatments: the rats were
given androgen for only 4 days and the dose of
ACTH used induced a maximal response in their
animals. The present study used a different
species, a relatively low dose of ACTH, a long
period of androgen stimulation, and extended
time observations in order to detect any
facilitatory effects of testosterone on the
action of ACTH.
The duration of androgen administration seems
to be an important factor. In our first
experiment we did not detect an androgen effect,
but did so in the second experiment. The only
factor that changed was that the animals
continued to receive androgen for 2 additional
weeks.
It is clear from the present experiment that
yawning and SYS are functionally distinct
behaviors, since testosterone itself is
effective in inducing yawning but not SYS
behavior, while ACTH is effective in inducing
SYS but not yawning behavior. Thus, separate
underlying neuroendocrine mechanisms may be
involved in these two behaviors. On the other
hand, it is premature to conclude that our
resuits represent a -synergistic- effect of the
two hormones as opposed to an "additive" effect.
Although TP by itself did not result in a
significant increase in stretch-yawning, there
was indeed a nonsignificant trend in that
direction. Further studies which vary both TP
and ACTH doses will be necessary before a
definitive answer to that question can be given.
The significance of these results for an
elucidation of peptide-steroid interactions ai
the neural level therefore remains to be tested.
However, it is possible from these results that
steroids could act on brain loci as well as on
the pituitary to modulate the central effect of
peptidergic neurons.
Other steroids have been shown to enhance the
effectiveness of peptidergic neurons for
behavioral systems: e.g., estrogen pretreatment
is required in order to induce female sexual
behavior with LHRH in rats. Those findings,
taken together with the results of the present
study, suggest that testosterone might alter the
sensitivity of hypothalamo-limbic-midbrain
circuits to ACTH, resulting in a combined
influence of these two hormones of the mediation
of SYS
« It is
ironic that testosterone "the male sex hormone,"
is more closely associated with the yawning rate
than with the mounting or intromitting rates
» Charles Phoenix
Sexual
steroids
exert several effects on both central
dopaminergic and oxytocinergic systems by acting
either at the genomic or membrane level
