Sensibilidade diferenciada dos núcleos anteroventral periventricular e arqueado ao estradiol como parte dos mecanismos de retroalimentação positiva e negativa sobre o eixo gonadal

• Ano de defesa: 2017
• Autor(a) principal: Patricia Costa Henriques
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Ciências Biológicas - Fisiologia e Farmacologia; UFMG
• Palavras-chave em Português: Estradiol; Hormônio luteinizante; Núcleo anteroventral periventricular; Núcleo arqueado; kisspeptina; Prolactina; Fisiologia; Núcleo arqueado do hipotálamo
• Link de acesso: http://hdl.handle.net/1843/35678

The preovulatory surge of luteinizing hormone (LH) is a key event responsible for ovulation and fertility in females. LH secretion is under estradiol (E2) control, through negative and positive feedback mechanisms that seem to evolve, respectively, the anteroventral periventricular nucleus (AVPV) of the preoptic area (POA) and the arcuate nucleus of the hypothalamus (ARC). Here, we investigated whether the AVPV and the ARC would respond differently to negative and positive feedback levels of E2. We used cycling rats on diestrus (DI) or proestrus (PRO) and ovariectomized (OVX) rats treated with oil or E2 (OVX+E2) in different doses. In experiment 1, serial blood collection was performed from 13:00 h to 18:00 h, in order to analyze E2, LH and prolactin (PRL) levels. After the last blood sampling, rats were perfused and the brains were processed for immunohistochemistry. In experiment 2, rats were decapitated and the POA and ARC were dissected for Kiss1, Esr1 and Esr2 mRNA analysis. Plasma E2 levels were elevated in PRO. E2 treatments increased plasma E2 levels, with rats treated with 20 μg/rat/day (OVX+E220) displaying similar values to PRO. Rats on PRO exhibited the preovulatory LH surge, which was replicated in OVX+E220 rats. On the other hand, rats treated with 1 μg/rat/day E2 (OVX+E21) showed only a decrease in LH levels compared to OVX rats. All E2 doses were able to promote surges of PRL secretion, likewise PRO. Consistent with the occurrence of the LH surge, expression of progesterone receptor (PR) and c-Fos in the AVPV increased only in PRO and OVX+E220 rats. However, in the ARC, both low and high levels of E2 in OVX+E21 and OVX+E220 rats, respectively, increased PR single labeling, PR coexpression in kisspeptin neurons and decreased the number of kisspeptin-immunoreactive (ir) neurons, to the levels found in DI and PRO rats. The percentage of estrogen receptor alpha (ERα)-ir neurons increased in the AVPV of OVX+E220 rats. RT-PCR revealed 9 dose-response effects of E2 on Kiss1 mRNA levels, with stimulation in the POA and inhibition in the ARC. Moreover, the ARC showed higher Esr1 expression compared to the AVPV in OVX+E21 rats, and a higher Esr1/Esr2 ratio regardless of the E2 levels. The results demonstrate that neurons in the ARC and AVPV respond selectively to low and high levels E2, respectively. Low E2 inhibits, while high E2 stimulates LH secretion. Thus, the differential sensitivity of ARC and AVPV neurons to E2 seems to play a role in the switch between negative- and positive-feedback effects on LH secretion.