Dopaminergic agonists, such as apomorphine
and oxytocin, are among the most potent inducers
of both penile erection and yawning in
laboratory animals. Several lines of
experimental evidence suggest that a
hypothalamic dopamine-oxytocin link plays a key
role in the expression of such symptomatology
and in male copulatory behavior. Interestingly,
sexual steroids exert several effects on both
central dopaminergic and oxytocinergic
systems by acting either at the genomic or
membrane level.
In particular, estrogens decrease the
activity of the majority of hypothalamic
dopaminergic neurons, including the
incerto-hypothalamic dopaminergic neurons which
are thought to play a key role in the expression
of the above responses. Estradiol benzoate and
progesterone alter the number and/or the
affinity of dopaminergic receptors; estradiol
benzoate prevents apomorphineinduced yawning,
and castration abolishes apomorphine-induced
penile erection.
Furthermore, estradiol benzoate influences
oxytocin-immunoreactive brain systems, and
induces the expression of oxytocin receptors in
several brain nuclei, especially in the
ventromedial nucleus of the hypothalamus, an
effect that resembles the induction of oxytocin
receptors in the pregnant uterus. Progesterone
further enhances estradiol benzoate-induced
oxytocin receptors, and is required after
estrogen priming for the expression of several
effects of oxytocin. Oxytocin receptors are also
increased in the ventromedial nucleus of
castrated male rats by testosterone, which
probably induces this effect after its
conversion to estradiol benzoate by brain
aromatase. However, progesterone was much less
effective in male rats than in female rats. The
above results prompted us to study the effect of
sexual steroids on apomorphine- and
oxytocin-induced penile erection and yawning in
intact and castrated male rats.
[...]
Discussion
The present results show that apomorphine-
and oxytocin-induced penile erection and yawning
are endocrine depenilent in male rats. Indeed,
castration dramatically decreases both
apomorphine- and oxytocin-induced penile
erection and yawning. This might be due to
the disappearance of testicular testosterone
that causes the depletion of brain testosterone
and its neural metabolites estradiol benzoate
and DHT. However, this explanation is
complicated by the finding that testosterone
supplementation in castrated rats restores
penile erection, but not yawning.
The ability of testosterone to restore
penile erection selectively is in agreement with
the hypothesis that testosterone has a
permissive role in the expression of penile
erection and sexual behavior, but not yawning.
In contrast, the selective restoration of
apomorphine- or oxytocin-induced yawning by
estradiol benzoate suggests a facilitatory role
of this testosterone metabolite in the
expression of yawning, but not of penile
erection. Estradiol benzoate, however, has been
found to be as effective as testosterone in
maintaining the copulatory behavior of castrated
animals. While the ineffectiveness of
progesterone in restoring apomorphine and
oxytocin responses in castrated rats was
expected because: the brain concentration of
this hormone in male rats is related to its
adrenal synthesis, and the brain of castrateo
male rats contain very low levels of
progesterone receptors, the inability of DHT to
restore penile erection was surprising. This
finding suggests that this testosterone
metabolite is not involved in the expression of
penile erection or yawning in the rat. However,
against this hypothesis a partial recovery of
both penile erection and yawning is induced by
supplementation with both DHT and estradiol
benzoate. This is in agreement with early
studies showing that DHT facilitates sexual
behavior and penile reflexes in intact male
rats, and restores copulation in castrated male
rats when given together with estradiol benzoate
suggesting that the two steroids act in
concert to modulate penile erection and
yawning.
The mechanisms by which castration prevents
and steroid supplementation restores either
penile erection and/ or yawning induced by
apomorphine or by oxytocin might be related
either to a reduced dopaminergic
neurotransmission that is reversed by
testosterone or estradiol benzoate + DHT, or to
a decrease in hypothalamic oxytocin-binding
sites reversed by testosterone as well as
estradiol benzoate supplementation without
altering neuronal immunoreactive oxytocinergic
pathways, or both.
The above findings support the hypothesis
that testosterone and its neural metabolites,
estradiol benzoate and DHT, are all necessary
for the expression of penile erection and
yawning and that their concentrations must
be within a specific range in order to allow
these behavioral manifestations. Accordingly,
completely different effects of the above
steroids on apomorphine- and oxytocin induced
penile erection and yawning are found in intact
male rats.
Indeed, in intact animals estradiol benzoate
prevents and progesterone potentiates yawning,
and testosterone does not modify penile erection
or yawning. While testosterone ineffectiveness
might reflect an already existing maximal
permissive role of the steroid on the above
responses in the presence of normal levels of
circulating testosterone estradiol benzoate
prevention of apomorphine-induced yawning may be
caused by a decrease in sensitivity and/or in
the number of central dopaminergic receptors or
by the inhibition of the neuronal targets of
dopamine, i.e. oxytocinergic neurons mediating
these behavioral responses.
However, the latter hypothesis is unlikely
because oxytocin-induced yawning is affected
much less by estradiol benzoate than that
induced by apomorphine, suggesting that:
in intact rats the activity of oxytocinergic
neurons mediating penile erection and yawning is
not modified significantly by estradiol
benzoate, unlike some magnocellular
oxytocinergic neurons
that estradiol benzoate-induced oxytocin
receptors are not involved in the expression of
these behavioral responses.
On the contrary, the potentiating effect of
progesterone on apomorphine and oxytocin-induced
yawning in intact rats might be due either to an
increase in dopaminergic receptors and/or their
affinity for the agonist, or to an increased
oxytocinergic transmission. The opposite effects
and the reciprocal antagonism of estradiol
benzoate and progesterone on yawning in intact
rats are not surprising, since the opposite
effects of the two steroids have been observed
in several experimental conditions. Since
estradiol benzoate effects are also prevented by
the specific nuclear estrogen receptor
antagonist tamoxifen, this might be related to
opposite functional genomic effects of the two
steroids. However, other explanations, such as
competition of the two steroids for the same
nuclear receptor or combined genomic and
non-genomic, ie. membrane effects of the two
steroids, cannot be ruled out. In view of the
structural similarity between progesterone and
testosterone, similar mechanisms might explain
the prevention by testosterone of estradiol
benzoate inhibition of apomorphine- and
oxytocin-induced yawning.
In contrast, the failure of DHT to prevent
estradiol benzoate effects suggests that this
testosterone metabolite does not interfere with
estradiol benzoate action either at the genomic
level or with estradiol benzoate receptor
binding.
Taken together, the ability of estradiol
benzoate and progesterone to modify apomorphine-
and oxytocin-induced yawning but not penile
erection in intact rats, and the differential
effect of testosterone and estradiol benzoate in
restoring penile erection and yawning,
respectively. suggest that the two behavioral
responses, although often seen in the same
experimental conditions, are mediated by
neuronal pathways differentially influenced by
sexual hormones. The identification of the exact
brain sites where sexual hormones act to modify
the above responses will help in identifying the
neural pathways mediating the expression of
penile erection and yawnig.
« 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
