Susana Isabel Ferreira da Silva de Sá ESTROGÉNIOS E ...

The studies incorporated in the present thesis contributed to clarify the role of sexual steroids
in inducing the plastic changes displayed by neurons of the ventrolateral division of the
hypothalamic ventromedial nucleus (VMNvl) across the ovarian cycle and to identify the
mechanisms by which estrogens exert this neurotrophic action. The studies were performed in
young Wistar rats. The variations in the morphology and connectivity pattern of VMNvl
neurons across the ovarian cycle were analyzed, at the ultrastructural level, in rats at diestrus 1
and proestrus phases of the ovarian cycle. The quantification of the synaptic contacts
established upon the VMNvl neurons of ovariectomized rats treated with estradiol or
progesterone, alone or in association with RU486, allowed to characterize the effects of
estrogen and progesterone in the induction of synaptic plasticity. In order to sort out the
estrogen receptor isoform through which estrogens act to induce synaptogenesis,
ovariectomized rats were treated with the specific agonists of the estrogen receptors α and β.
To assess the role of neuronal afferents as mediators of the estrogen influence in the induction
of new synapses and in the expression of progesterone receptors in the VMNvl, studies were
done in ovariectomized rats that, after VMN deafferentation, were treated with estradiol.
The results showed that there is a positive correlation between the circulating levels of
sex steroid hormones and the size of the cytoplasmic organelles involved in protein synthesis
and the number of nuclear pores and synapses established upon VMNvl neurons. In addition,
they evinced that these effects are the leading cause of the variations in the magnitude of the
sexual dimorphisms displayed by several morphological features of the VMNvl along the
ovarian cycle. Data obtained also demonstrated that progesterone does not promote the
formation of new synapses in the VMNvl, and that the cyclic variations that occur in the
number of VMNvl synapses over the estrous cycle is exclusively dependent on estrogen
actions. The finding that the synaptogenic effects of estradiol and of the specific agonists of
the α and β subtypes of estrogen receptor were very similar allowed to draw the conclusion
that these estrogen effects are mediated by the activation of its nuclear receptors. Moreover,
the observation that VMN deafferentation prevented the estradiol-induced formation of new
synapses showed that the synaptogenic effects of estrogens in the VMNvl are indirect and
mediated by the neural afferents originating from regions of the brain that are estrogen-
sensitive. Lastly, the finding that VMN deafferentation did not interfere with the induction of
progesterone receptors by estradiol showed that to promote this effect, known to be critical
for the induction of the female sexual behavior, estrogens act directly upon VMNvl neurons.
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