Estudos hodológicos sugerem um dimorfismo sexual das projeções da área incerto-hipotalâmica (IHy), com áreas relevantes para o controle reprodutivo mais densamente inervadas em fêmeas. Estudos funcionais mostraram que o RNAm do precursor do hormônio concentrador de melanina (ppMCH) varia apenas na IHy, durante o ciclo estral e é reduzido em ratas em anestro induzido por restrição alimentar (RA). Nosso objetivo foi analisar em camundongos fêmeas, as alterações na morfologia de útero e ovários e na expressão do RNAm do ppMCH da IHy ocasionadas pelo anestro induzido por RA. Para isso, camundongos fêmeas C57BL/6 foram distribuídas em controle (C), restrito (R; ração = 70% do C) e realimentado (RR). Os animais R foram perfundidos após 4, 8 e 12 dias para coleta de encéfalo, útero e ovários. Houve um aumento no número de folículos antrais nos animais R12 comparados ao R4 e redução da área uterina nos animais R8 com recuperação dos RR. Não foi possível detectar alterações na expressão do RNAm do ppMCH na IHy. / Hodological studies suggest a sexual dimorphism of the incerto-hypothalamic area (IHy) projections since relevant areas to the reproductive control are more densely innervated in females. Functional studies have shown that the MCH precursor mRNA (ppMCH) varies only in the IHy during the estrous cycle of an intact rat and is decreased in anestrus rats induced by food restriction. We aim to analyze, in female mice, the changes in uterine and ovarian morphology and expression of IHy ppMCH mRNA in anestrus induced by food restriction. For this, C57BL/6 female mice were distributed in control (C), food restricted (FR) and refed (RR). FR were perfused after 4, 8 and 12 days to collect the brain, uterus and ovaries. Our results show an increased number of antral follicles of R12 compared to R4 and a reduction in the uterine area of R8 with restoration in RR. It was not possible to detect changes in ppMCH mRNA expression in IHy.

<p>Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. </p><p>Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. </p><p>The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition.</p><p>The partial 5-HT_1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT₂ receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. </p><p>The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. </p><p>Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.</p>

Premenstrual dysphoria, so severe that it affects the lives of the women afflicted, is the condition studied in this thesis. Physiological and pharmacological mechanisms of pathogenetic relevance were investigated. Women with premenstrual dysphoria showed a stronger and less dampened response of LH to an estradiol challenge than asymptomatic women, indicating an altered neuroendocrine regulation. In women with premenstrual dysphoria, the LH response was correlated to the severity of irritability and bloating, and the early FSH response was correlated to the severity of depressed mood. The positron-emission study showed strong, consistent correlations between worsening of mood symptoms and a decrease in brain trapping of the immediate serotonin precursor, from the mid-follicular to the late luteal phase in women with premenstrual dysphoria. The strongest correlations were seen for the cardinal mood symptoms of premenstrual dysphoria, and for their opposites. Physical symptoms showed weaker or no correlations with the exception of nociceptive symptoms from erogenous body regions which showed positive correlations to serotonin precursor trapping in the right caudate nucleus. The findings are consistent with the serotonin hypothesis of premenstrual dysphoria, and might possibly explain the observed effects of serotonin-augmenting drugs in this condition. The partial 5-HT1A receptor agonist buspirone was superior to placebo in the treatment of premenstrual dysphoria. The weak SRI and 5-HT2 receptor antagonist nefazodone was not superior to placebo. For women with premenstrual dysphoria in need of medication and who do not tolerate SRIs because of the sexual sideeffects, buspirone may be an alternative drug, since it had no adverse effects on sexual function. The prevalence of polycystic ovaries and serum levels of androgens were not higher in women with premenstrual dysphoria than in their asymptomatic counterparts. The findings are not consistent with the hypothesis that irritability in women with premenstrual dysphoria is induced by elevated testosterone levels. Thesis results, which are in line with the serotonin hypothesis of premenstrual dysphoria, may imply that increased brain sensitivity is one of the factors underlying severe premenstrual mood symptoms, thereby further supporting a common serotonergic dysregulation in this condition.