Papel da prolactina durante desenvolvimento prostático em ratos: avaliação da morfogênese glandular, proliferação e diferenciação das células epiteliais
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Data
2017-02-22
Autores
Camargo, Ana Carolina Lima [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A próstata é uma glândula acessória do sistema genital masculino e, além da dependência androgênica para o seu desenvolvimento e homeostasia, é influenciada por hormônios não esteróides, entre eles a prolactina (PRL). Estudos em modelos animais demonstraram que a PRL pode atuar com efeito anabólico sobre a glândula prostática. Assim, nosso objetivo foi investigar os efeitos da modulação de PRL sobre o desenvolvimento e maturação da próstata ventral (PV) de ratos. Foram utilizados ratos machos Sprague Dawley (DPN 90) divididos em 6 grupos (n=6): Grupo controle (CT): receberam solução salina; Prolactina (PRL): Prolactina (0,3mg/kg); Bromocriptiona (BR): inibidor de PRL (0,4mg/kg). Todos os animais foram submetidos diariamente (via subcutânea) do dia pós-natal 12 (DPN12) até os DPN 21 ou 35. Os animais foram anestesiados, pesados e posteriormente foram eutanasiados. O sangue e os lobos da PV foram coletados, pesados e processados para análises morfológicas, de western blot (WB) e RT qPCR. O tratamento com PRL induziu aumento de peso corpóreo dos animais no DPN35 comparado aos outros grupos. Histologicamente houve maior acumulo de screção no lúmen e diminuição do compartimento epitelial nos grupos PRL e BR comparados ao CT no DPN35. A reação imunohistoquímica para Ki67 demonstrou aumento de células proliferativas nos grupos tratados com PRL. A quantificação de PCNA confirmou estes dados, com aumento significante no grupo PRL35. A intensidade de reação imunohistoquímica para AR foi maior no grupo PRL35. A quantificação de AR por WB confirmou esses dados. A expressão gênica do PRLR aumento no DPN21, enquanto que no DPN35 os grupos PRL e BR diminuíram, em Stat3 aumento nos grupos BR no DPN21 e 35, enquanto que Stat5 não houve diferença nos diferentes grupos. A expressão proteica de PRL aumentou no PRL21, no DPN35 diminuiu em PRL e BR, o PRLR não teve diferença entre os grupos experimentais. A quantificação proteica de STAT3 aumento nos grupos PRL e BR em ambas as idades, no STAT5 AB e prostateína aumentou nos grupos PRL em relação aos outros dois grupos no DPN35. A expressão proteica de CK18 aumentou nos grupos tratados com BR no DPN21 e 35, em NKX3.1 o aumento no PRL em relação aos outro grupo no DPN21. Nossos resultados demonstram que a modulação de PRL interfere com a morfofisiologia prostática, aumentando a resposta proliferativa e atividade secretora, em especial nos animais tratados por período prolongado. Estes dados revelam o importante papel da PRL sobre o desenvolvimento prostático.
The prostate gland is an accessory gland of the male genital system and, in addition to androgenic dependence for its development and homeostasis, is influenced by non-steroidal hormones, among them the prolactin (PRL). Studies in animal models have shown that PRL can act with an anabolic effect on the prostate gland. Thus, our objective was to investigate the effects of PRL modulation on the development and maturation of the ventral prostate (VP) of rats. Male Sprague Dawley rats (PND 90) were divided in 6 groups (n= 6): Control group (CT) that received saline solution; Prolactin group (PRL) that received Prolactin (0.3mg/kg); Bromocriptiona group (BR) that received PRL inhibitor (0.4mg/kg). All animals were submitted daily (subcutaneously) from postnatal day 12 (PND12) to PND 21 or 35. The animals were anesthetized, weighed and euthanized. Blood and VP lobes were collected, weighed and processed for morphological analyzes, western blot (WB) and RT qPCR. Treatment with PRL induced body weight gain in PND35 compared to the other groups. Histologically, there was an increase in the luminal compartment and a decrease in the epithelial compartment in the PRL and BR groups compared with CT on PND35. The immunohistochemical reaction for Ki67 demonstrated proliferation of proliferative cells in the groups treated with PRL on PND35. The PCNA quantification confirmed these data, with a significant increase in the PRL35 group. The intensity of reaction for AR was higher in the PRL35 group. Quantification of AR by WB confirmed these data. The gene expression of the PRLR increased in the PND21, whereas on PND35 the PRL and BR groups decreased, in Stat3 increased in the BR groups on PND21 and 35, whereas in the Stat5 groups there was no difference in the different groups. Protein expression of PRL increased in PRL21, on PND35 decreased in PRL and BR, PRLR had no difference between the experimental groups. The protein quantification of STAT3 increased in the PRL and BR groups in both ages, STAT5 AB and prostatein increased in the PRL groups compared with other two groups on PND35. Protein expression of CK18 increased in the groups treated with BR on PND21 and 35, on NKX3.1 the increase in PRL compared to other groups on PND21. Our results demonstrate that PRL modulation interferes with prostate morphophysiology, increasing the proliferative response and secretory activity, especially in animals treated for a long period. These data reveal the relevant role of PRL in prostate development.
The prostate gland is an accessory gland of the male genital system and, in addition to androgenic dependence for its development and homeostasis, is influenced by non-steroidal hormones, among them the prolactin (PRL). Studies in animal models have shown that PRL can act with an anabolic effect on the prostate gland. Thus, our objective was to investigate the effects of PRL modulation on the development and maturation of the ventral prostate (VP) of rats. Male Sprague Dawley rats (PND 90) were divided in 6 groups (n= 6): Control group (CT) that received saline solution; Prolactin group (PRL) that received Prolactin (0.3mg/kg); Bromocriptiona group (BR) that received PRL inhibitor (0.4mg/kg). All animals were submitted daily (subcutaneously) from postnatal day 12 (PND12) to PND 21 or 35. The animals were anesthetized, weighed and euthanized. Blood and VP lobes were collected, weighed and processed for morphological analyzes, western blot (WB) and RT qPCR. Treatment with PRL induced body weight gain in PND35 compared to the other groups. Histologically, there was an increase in the luminal compartment and a decrease in the epithelial compartment in the PRL and BR groups compared with CT on PND35. The immunohistochemical reaction for Ki67 demonstrated proliferation of proliferative cells in the groups treated with PRL on PND35. The PCNA quantification confirmed these data, with a significant increase in the PRL35 group. The intensity of reaction for AR was higher in the PRL35 group. Quantification of AR by WB confirmed these data. The gene expression of the PRLR increased in the PND21, whereas on PND35 the PRL and BR groups decreased, in Stat3 increased in the BR groups on PND21 and 35, whereas in the Stat5 groups there was no difference in the different groups. Protein expression of PRL increased in PRL21, on PND35 decreased in PRL and BR, PRLR had no difference between the experimental groups. The protein quantification of STAT3 increased in the PRL and BR groups in both ages, STAT5 AB and prostatein increased in the PRL groups compared with other two groups on PND35. Protein expression of CK18 increased in the groups treated with BR on PND21 and 35, on NKX3.1 the increase in PRL compared to other groups on PND21. Our results demonstrate that PRL modulation interferes with prostate morphophysiology, increasing the proliferative response and secretory activity, especially in animals treated for a long period. These data reveal the relevant role of PRL in prostate development.
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Palavras-chave
Próstata, Prolactina, Morfologia, Desenvolvimento, Prostate, Prolactin, Morphology, Development