Relativa influência da prolactina, sua inibição e combinação com testosterona sobre a próstata de ratos castrados: comparação entre recrescimento glandular, diferenciação celular e atividade secretora
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Data
2017-02-22
Autores
Constantino, Flávia Bessi [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A próstata é uma glândula do sistema genital masculino que possui grande importância na fertilidade. Estudos clássicos evidenciaram que para que se inicie o desenvolvimento prostático é necessário a presença de andrógeno produzido pelos testículos fetais. Porém, além da estimulação androgênica, estudos apontam para outros hormônios que também atuam na próstata como a Prolactina (PRL). PRL é um hormônio que é principalmente secretado por células lactotróficas da hipofise anterior e está envolvido em muitos processos biológicos, incluindo lactação e reprodução. Assim, investigamos se a modulação da sinalização PRL altera a morfofisiologia da próstata ventral (VP) em ratos castrados. Os ratos Sprague Dawley adultos (n = 6) foram castrados e após 21 dias divididos em 10 grupos experimentais: Castrado Controle (CC): animais castrados que não receberam tratamento; Castrado+testosterona (T): animais castrados que receberam T (4mg / kg); Castrado+PRL (PRL): animais castrados recebendo PRL (0,3 mg / kg); Castrado+T+PRL (TPRL): animais castrados que receberam associação de T e PRL; e Castrado+BR (BR): animais castrados que receberam Bromocriptina (BR) (0,4mg / kg). Grupo Controle: animais intactos (CTR). Os animais foram tratados durante 3 ou 10 dias consecutivos. Ao fim dos tratamentos, os animais foram anestesiados, eutanizados e a prostata ventral (VP) foi removida, pesada e processada para análise histológica e Western blot. O peso corporal não se alterou entre os grupos experimentais. A atrofia glandular foi induzida pela castração e a administração de andrógenos induziram o recrescimento. Não houve diferença entre o peso da VP dos grupos T e TPRL em ambas as idades. PRL ou BR não teviveram efeito sobre o peso glandular. A castração levou a uma diminuição na proliferação celular, na expressão de AR, STAT3 e 5, enquanto T ou TPRL induziram resposta proliferativa, maior expressão de AR, STAT3 e 5. O tratamento com BR durante o dia 3 ou PRL durante 10 dias aumentou STAT3. O tratamento com PRL e BR não alterou a proliferação celular ou a expressão de AR, mas aumentou a expressão da proteína do receptor de PRL (PRLR). A administração de T e TPRL não alterou este parâmetro. A prostateína diminuiu em todos os grupos tratados durante 3 e 10 dias, excepto nos animais dos grupos T10 ou TPRL10. Embora observássemos a ativação da sinalização de PRL, esta não exerceu efeito anabólico na VP de ratos castrados. A administração de PRL a 0,3 mg/kg administrada durante 3 ou 10 dias consecutivos não foi suficiente para superar a deficiência de andrógeno na próstata. Da mesma forma, não há involução glandular adicional no grupo castrado BR. Conclui-se que, apesar de estimular a via de sinalização a jusante, a PRL não atua sobre VP na ausência ou na presença de níveis supra-fisiológicos de testosterona.
Prolactin (PRL) is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction. Thus, we investigated whether the modulation of the PRL signaling alters the ventral prostate (VP) morphophysiology in castrated rats. Adult Sprague Dawley rats (n = 6) were castrated for 21 days and after divided into 10 experimental groups: Castrated Control (CC): castrated animals that did not receive treatment; Castrated+testosterone (T): castrated animals that received T (4mg/kg); Castrated+PRL (PRL): castrated animals receiving PRL (0.3 mg/kg); Castrated+T+PRL (TPRL): castrated animals that received association of T and PRL; and Castrated+BR (BR): castrated animals that received Bromocriptine (BR) (0.4mg / kg). Control group: intact animals (CTR). The animals were treated for 3 or 10 consecutive days. At the end of experiment, the animals were anesthetized, euthanized and the VP lobes were removed, weighed and processed for histological and western blot analyzes. Body weight did not change between the experimental groups. Castration induced glandular atrophy and androgen administration induced glandular regrowth. There was no difference between VP weight from T and TPRL groups in both ages. PRL or BR had no effect on glandular weight. Castration led to a decrease in cell proliferation, AR and STAT3 and 5 expressions, whereas T or TPRL replacement induced proliferative response, AR and STAT3 and 5 expressions. Treatment with BR for day 3 or PRL for 10 days increased STAT3, respectively. PRL and BR treatment did not alter cell proliferation or AR expression, but increased PRL receptor (PRLR) protein expression. Administration of T and TPRL did not alter this parameter. Prostatein decreased in all groups treated for 3 and 10 days, except in the animals of the T10 or TPRL10 groups. Thus, the administration of PRL at 0.3 mg/kg administered for 3 or 10 consecutive days do not exert anabolic effect on the VP of castrated rats. Although we observed activation of PRL signaling, this was not enough to overcome the prostatic androgen deficiency. Likewise, there is no additional glandular involution in BR castrated group. We conclude that despite stimulating downstream signaling pathway, PRL does not act on VP in the absence or in the presence of supra physiologic levels of testosterone.
Prolactin (PRL) is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction. Thus, we investigated whether the modulation of the PRL signaling alters the ventral prostate (VP) morphophysiology in castrated rats. Adult Sprague Dawley rats (n = 6) were castrated for 21 days and after divided into 10 experimental groups: Castrated Control (CC): castrated animals that did not receive treatment; Castrated+testosterone (T): castrated animals that received T (4mg/kg); Castrated+PRL (PRL): castrated animals receiving PRL (0.3 mg/kg); Castrated+T+PRL (TPRL): castrated animals that received association of T and PRL; and Castrated+BR (BR): castrated animals that received Bromocriptine (BR) (0.4mg / kg). Control group: intact animals (CTR). The animals were treated for 3 or 10 consecutive days. At the end of experiment, the animals were anesthetized, euthanized and the VP lobes were removed, weighed and processed for histological and western blot analyzes. Body weight did not change between the experimental groups. Castration induced glandular atrophy and androgen administration induced glandular regrowth. There was no difference between VP weight from T and TPRL groups in both ages. PRL or BR had no effect on glandular weight. Castration led to a decrease in cell proliferation, AR and STAT3 and 5 expressions, whereas T or TPRL replacement induced proliferative response, AR and STAT3 and 5 expressions. Treatment with BR for day 3 or PRL for 10 days increased STAT3, respectively. PRL and BR treatment did not alter cell proliferation or AR expression, but increased PRL receptor (PRLR) protein expression. Administration of T and TPRL did not alter this parameter. Prostatein decreased in all groups treated for 3 and 10 days, except in the animals of the T10 or TPRL10 groups. Thus, the administration of PRL at 0.3 mg/kg administered for 3 or 10 consecutive days do not exert anabolic effect on the VP of castrated rats. Although we observed activation of PRL signaling, this was not enough to overcome the prostatic androgen deficiency. Likewise, there is no additional glandular involution in BR castrated group. We conclude that despite stimulating downstream signaling pathway, PRL does not act on VP in the absence or in the presence of supra physiologic levels of testosterone.
Descrição
Palavras-chave
Próstata, Castração, Testosterona, Prolactina, Prostate, Castration, Testosterone, Prolactin