RESUMO

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Assuntos

RESUMO

Neuroprotective effects of short prolactin (PRL) pre-treatment against kainic acid (KA)-induced damage include neuron loss avoidance in all hippocampal regions and attenuation of seizures. Recent evidence points PRL receptor (PRL-R) as mediator of such neuroprotective effects and seizures as regulators of neuronal marker transcript expression in the hippocampus. Here, we investigated if a daily PRL dose of 100 µg or vehicle for 14 days in ovariectomized rats (OVX) prevents neuron loss induced by KA administered on the third day of PRL treatment in a systemic single dose of 7.5 mg/kg or vehicle, and promotes PRL-R, vesicular glutamate transporter 1 (VGLUT1) and glutamic acid decarboxylase 65 (GAD65) expression changes in the hippocampus of sacrificed rats 27 days after the KA administration. Immunostaining for Neu-N and PRL-R revealed significant neuron number and PRL-R expression reduction induced by KA that was prevented and turned into overexpression respectively in all hippocampal regions when PRL was added; while VGLUT1,and GAD65 immunostaining displayed expression decrease in the CA1 of injured rats, prevented in the last case and turned into VGLUT1, overexpression when administered PRL. These data indicate that chronic PRL administration before damage induces hippocampal neuroprotection associated with PRL-R and VGLUT1 overexpression, the latter in a regiondependent way.

Assuntos

RESUMO

O diabetes mellitus tipo 1 é uma doença metabólica, caracterizada pela desregulação glicêmica, que ocorre devido a um ataque autoimune. A insulinoterapia é o tratamento clássico para o DM1. Contudo, alguns pacientes que apresentam essa doença não respondem de forma eficiente a este tratamento e apresentam episódios frequentes de hipoglicemia severa e despercebida (pacientes hiperlábeis). Essas complicações comprometem de forma significativa a qualidade de vida dessas pessoas. O transplante de ilhotas é uma importante alternativa para o tratamento de pacientes hiperlábeis com DM1. No entanto, essa terapia apresenta restrições como a necessidade de mais de um doador por transplante e significativa morte das ilhotas devido ao estresse provocado pelo procedimento de isolamento, além da morte promovida pelo sistema imune do paciente nos primeiros momentos pós-transplante. A autofagia é um mecanismo de reciclagem de componentes citoplasmáticos que é fundamental para a homeostase celular. Em condições de estresse, este mecanismo é ativado acima do seu nível basal, promovendo a degradação de agregados proteicos e organelas defeituosas, evitando assim, danos celulares que comprometam a viabilidade da célula. Trabalhos realizados por nosso grupo têm mostrado a citoproteção que PRL promove em células-beta, reduzindo a apoptose induzida por citocinas pró-inflamatórias. Também demonstramos o papel essencial de HSPB1 na inibição de apoptose induzida por PRL após o tratamento com citocinas. Além disso, resultados recentes de nosso laboratório mostraram um aumento nos níveis de autofagia em células-beta após sua exposição a citocinas, bem como uma restauração a níveis normais na presença de PRL. Visando um melhor entendimento do papel da PRL na modulação da autofagia em células-beta, o objetivo desse projeto foi estudar se HSPB1 também é essencial no mecanismo de regulação da autofagia induzido por PRL.Para tal, fizemos experimentos em modelos de células-beta MIN6, MIN6 silenciadas para HSPB1 (MIN6-shHSPB1) e MIN6 com sequencia short hairpin aleatória (MIN6- SsC), medindo a morte celular através de ensaios de viabilidade, e ensaios de western blot para avaliar os níveis de marcadores de autofagia e fluxo autofágico (degradação de autofagossomos), tratando as células com citocinas, prolactina e indutores ou inibidores de autofagia. Os resultados mostraram que a modulação da autofagia ocasionada pela prolactina em células-beta se dá, em parte, através de HSPB1. O tratamento com prolactina foi capaz de inibir a morte celular induzida por citocinas, mesmo na presença de cloroquina, um bloqueador de autofagia, o que nos levou a concluir que a autofagia não é uma via envolvida na citoproteção de células beta induzida por PRL. Os resultados gerados nesse estudo contribuíram para uma melhor compreensão dos eventos moleculares induzidos por PRL em células-beta, e poderão permitir a inferência de novas abordagens que melhorem a citoproteção, cultura e transplante dessas células em pacientes com diabetes tipo 1

Type 1 diabetes mellitus is a metabolic disease characterized by glycemic dysregulation, which occurs due to an autoimmune destruction of beta-cells. Insulin therapy is the gold standard treatment for DM1. However, some DM1 patients do not respond efficiently to this treatment and suffer frequent episodes of severe hypoglycemia unawareness. Since this complication jeopardizes the quality of life of these people, Islet transplantation is a therapeutic alternative indicated to treat these patients. However, besides the lack of enough organ donors, the loss of beta cells during both the isolation as well as the infusion of islets into the recipient induce a great estresse and thus a significant cell death is one of the drawbacks of this procedure. Autophagy is a mechanism of recycling cytoplasmic components and is essential for cellular homeostasis. Under estresse conditions, this mechanism is activated above basal levels, promoting the degradation of protein aggregates and defective organelles, thus avoiding cell damage that could compromise cell viability. Studies carried out by our group have shown not only that PRL promotes cytoprotection in beta-cells, reducing pro-inflammatory cytokines-induced apoptosis, but also that HSPB1 plays an essential role in this inhibition of apoptosis mediated by PRL after treatment with cytokines. Moreover, recent results from our laboratory showed an increase in autophagy levels in beta-cells after exposure to cytokines, as well as a restauration to normal levels in the presence of PRL. In order to better understand the role of PRL in the modulation of autophagy in these cells, the aim of this project is to study whether HSPB1 is also essential in the mechanism of autophagy regulation induced by PRL. Using MIN6 beta cell models where HSPB1 was silenced (MIN6-shHSPB1) or not (MIN6-SsC), we studied cell death by viability assays. Moreover, western blot assays were performed in order to assess levels of autophagy and autophagic flux markers in the cells.Our results showed that HSPB1 in one of the mediators of PRL-induced modulation of autophagy. Nevertheless, since hormonal treatment was still able to inhibit cytokinesinduced cell death even in the presence of chloroquin, an autophagy blocker, we conclude that autophagy is not a signaling pathway involved in PRl-induced beta-cell cytoprotection. Altogether, the results shown in this study may help to increase the knowledge of the molecular events induced by PRL in beta-cells, and may allow to infer new approaches to improve cytoprotection, culture and transplantation of these cells into type 1 diabetic patients

Assuntos

RESUMO

UNLABELLED: Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. AIMS: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. MATERIAL AND METHODS: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. RESULTS: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. CONCLUSION: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies.

Assuntos

RESUMO

Several reports have shown that prolactin (PRL) plays a role in prostatic growth, but few studies considered the role of PRL in the process of prostatic inflammation. Young (45 ± 5 days old) and adult (75 ± 5 days old) male Wistar rats were subcutaneously injected daily with domperidone (4.0 mg.kg-1) to maintain high serum PRL levels. The animals were treated for 15, 30, 45 or 60 days. Blood and prostate samples were collected at the end of each treatment for PRL dosage and histological analysis, respectively. Only young animals treated with DOMP for 15 and 30 days displayed inflammatory infiltrate in the prostate. These results confirm literature data in regards to PRL involvement in inducing prostate inflammation. Moreover, it was concluded that young animals are more susceptible then adults to the PRL action concerning prostate inflammation(AU)

A prolactina (PRL) influencia o crescimento prostático, entretanto poucos estudos investigaram o papel da PRL na inflamação prostática. Ratos Wistar jovens (45 ± 5 dias de idade) e adultos (75 ± 5 dias de idade) receberam injeções subcutâneas diárias de domperidona (4,0 mg.kg-1) para manter níveis séricos altos de PRL. Os animais foram tratados por 15, 30, 45 ou 60 dias. Amostras de sangue e próstata foram coletadas ao final dos tratamentos para dosagem de PRL e análise histológica, respectivamente. Apenas os animais jovens tratados com domperidona por 15 e 30 dias apresentaram infiltrado inflamatório na próstata. Esses resultados confirmaram a participação da PRL na indução da inflamação prostática. A conclusão obtida foi que animais jovens são mais susceptíveis à ação da PRL na inflamação da próstata que os adultos(AU)

Assuntos

RESUMO

Several reports have shown that prolactin (PRL) plays a role in prostatic growth, but few studies considered the role of PRL in the process of prostatic inflammation. Young (45 ± 5 days old) and adult (75 ± 5 days old) male Wistar rats were subcutaneously injected daily with domperidone (4.0 mg.kg-1) to maintain high serum PRL levels. The animals were treated for 15, 30, 45 or 60 days. Blood and prostate samples were collected at the end of each treatment for PRL dosage and histological analysis, respectively. Only young animals treated with DOMP for 15 and 30 days displayed inflammatory infiltrate in the prostate. These results confirm literature data in regards to PRL involvement in inducing prostate inflammation. Moreover, it was concluded that young animals are more susceptible then adults to the PRL action concerning prostate inflammation...

A prolactina (PRL) influencia o crescimento prostático, entretanto poucos estudos investigaram o papel da PRL na inflamação prostática. Ratos Wistar jovens (45 ± 5 dias de idade) e adultos (75 ± 5 dias de idade) receberam injeções subcutâneas diárias de domperidona (4,0 mg.kg-1) para manter níveis séricos altos de PRL. Os animais foram tratados por 15, 30, 45 ou 60 dias. Amostras de sangue e próstata foram coletadas ao final dos tratamentos para dosagem de PRL e análise histológica, respectivamente. Apenas os animais jovens tratados com domperidona por 15 e 30 dias apresentaram infiltrado inflamatório na próstata. Esses resultados confirmaram a participação da PRL na indução da inflamação prostática. A conclusão obtida foi que animais jovens são mais susceptíveis à ação da PRL na inflamação da próstata que os adultos...

Assuntos

RESUMO

BACKGROUND: Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus. RESULTS: Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor. CONCLUSIONS: We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.

Assuntos

RESUMO

A importância da dosagem de prolactina reside principalmente no fato de sua utilização diagnóstica em alterações da hipófise anterior. Alguns medicamentos, como a fluoxetina, podem alterar a secreção da prolactina. Assim, o foco deste trabalho foi ode avaliar a real importância de se considerar o uso da fluoxetina, um inibidor seletivo da recaptação da serotonina (ISRS), como um interferente na interpretação dos valores de dosagens laboratoriais da prolactina em mulheres. Foram analisados dados de 95 mulheres, com idade entre 15 e 70 anos, que realizaram dosagens séricas de prolactina. As mulheres em tratamento com a fluoxetina apresentaram um aumento significativo de prolactina. Este aumento foi maior em mulheres com até 29 anos, onde chegou a níveis considerados patológicos, diminuindo de uma maneira inversamente proporcional com o aumento da faixa etária. Acima dos 45 anos, onde a maioria das mulheres encontra-se na menopausa, os valores de prolactina não se alteram com o uso da fluoxetina.

Assuntos

RESUMO

It is known that prolactin (PRL) is produced within the brain and numerous central actions of the hormone have been reported. In anesthetized lactating rats, central administration of PRL, i.e., intracerebroventricular (icv) or intrathecally (it), facilitated milk ejection (ME) by depressing the sympathetically mediated facilitatory tone of the mammary ductal system. However, it is not known whether or not the same effects and similar mechanisms take place in conscious rats after PRL administration. In the present study, the effects of centrally administered PRL, i.e., icv or it, on ME was determined in both conscious and anesthetized rats. In conscious rats, the rate of ME was determined by applying a 15-min period of suckling by the litter, following a 6-h period of isolation. In anesthetized rats, intramammary pressure (IMP) responses of the mammary glands to exogenous oxytocin (OT) were recorded. The results showed that, whereas in anesthetized rats, increased responsiveness of the mammary glands to OT were observed after PRL administration, an intense inhibition of ME occurred in conscious rats. Because, in conscious and anesthetized rats, these effects were prevented by prior administration of the beta-adrenergic blocker propranolol (PROP) to the mothers, this suggests that the PRL effects on ME are modulated through sympathomimetic and sympatholytic actions in conscious and anesthetized rats, respectively. Thus, as shown by ductal tone measurements, in conscious, but not in anesthetized rats, the effect of PRL was associated with increased ductal constriction within the mammary glands; an effect that was mimicked by icv administration of the beta-adrenergic agonist isoproterenol (ISOP) and that was prevented by PROP. Further, the sympatholytic action of icv-PRL in anesthetized rats prevented the effect on ductal tone of both icv-PRL in conscious rats and of ISOP in anesthetized rats. Taken together, these results clearly suggest that the central effects of PRL on ME are modulated by adrenergic mechanisms.

Assuntos

RESUMO

The possible role of prolactin (PRL) in human immunodeficiency virus (HIV) infection is unknown, despite the modulatory role of this hormone in humoral and cell-mediated immune responses. Recent studies have evidenced: (a) intralymphocyte synthesis of dopamine (DA) which down-regulates their own proliferation and differentiation; (b) decreased DA but increased PRL concentrations in cerebrospinal fluid of HIV-infected men; and (c) diminished hypothalamic DA tone in HIV-infected men. The present hypothesis proposes that, in HIV-infected men, a diminished generalized DA tone exists to stimulate human lymphocyte proliferation and differentiation at a maximum possible rate by: (1) decreasing the inhibitory influence of intralymphocyte DA; and (2) maintaining pituitary and extrapituitary (i.e. lymphocyte) PRL synthesis and release as high as possible. If this hypothesis is correct, it may have a potentially important therapeutic implication: the possibility to rebuild the battered immune system in HIV-infected patients from inside the body in a physiologic manner by the parenteral administration of recombinant human PRL.

Assuntos

RESUMO

A prolactina e um hormonio sintetizado na adenoipofise, na hipofise fetal e pelas celulas deciduais, apresentando açäo sobre as mamas, o eixo hipotalamo-hipofise-ovario, na maturidade fetal e osmoreguladora no volume de liquido amniotico. Os autores analisam os mecanismos reguladores da secreçäo da prolactina e seus efeitos biológicos relacionados a reproduçäo

Assuntos

RESUMO

The distribution of labeled hGH, oGH and mPRL in different tissues of MT-bGH transgenic and normal mice was investigated using an in vivo technique. This technique allows comparisons of tissue uptake of radioactivity after the labeled hormone was injected alone (20 ng/50 g BW) or together with an excess (300 micrograms/50 g BW) of unlabeled hormone. Liver, kidney and spleen are the organs that concentrate a significant amount of radioactivity 20 min after the injection of labeled hormones, but the uptake of radioactivity decreased in the presence of unlabeled hormones only in the liver. Graphical analysis showed that the disappearance curves were described by the sum of 3 compartments alpha, beta and gamma. The first two are similar in transgenic and in normal mice but the third had a t1/2 of 56 +/- 9 min in transgenic and 71 +/- 8 min in normal mice. The inhibition of liver uptake was related to the dose of unlabeled hormone injected and a half maximal displacement was obtained with 4 micrograms and 10 micrograms of hGH per 50 g of body weight for normal and transgenic mice, respectively. The 125I-hGH taken up in vivo by the liver of transgenic mice was bound to a molecular species with Stokes radius of approximately 64 A (which is consistent with the molecular size reported for the hormone-receptor complex).(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

RESUMO

Se analizan 926 historias clínicas de la consulta externa de las de endocrinología ginecológica e infertilidad para conocer la frecuencia en los niveles de prolactina (PRL) en las pacientes que asistieron al Instituto Materno Infantil de Bogotá en el período del 1§ de enero de 1984 al 31 de marzo de 1989. De los 926 casos se les solicitó PRL a 210 (22.6 por ciento), de estos, 152(72.4 por ciento) reportó niveles normales y elevada mayor de 20 ng/ml en 58 pacientes(27.6 por ciento), distribuidos así; oligomenorrea 16(27.5 por ciento),Amenorrea 2 RIA 11(18.9 por ciento),galactorrea 9 (15.5 por ciento), polimenorrea 8 (13.8 por ciento), amenorrea-galactorrea 4 e infertilidad 4 para (6.8 por ciento). Los niveles de PRL de acuerdo al motivo de consulta presentó los siguientes niveles: amenorrea-galactorrea 225.3 ng/ml, amenorrea IRIA 128.0 ng/ml, oligomenorrea 58.14 ng&ml, galactorrea 53.5ng/ml , polimenorrea 37.5 ng/ml. En los casos de hiperprolactinemia de 21 sillas turcas analizadas 9 (19.3 por ciento) fueron anormales, de 15 campimetrías 4 (26.7 por ciento) presentaron alteraciones y de 9 TAC 3 resultaron con alteración a nivel hipofisiario. La etiología no fue posible determinarla en 39 casos (53.5 por ciento), debida a hipotiroidismo 5 (8.6 por ciento), microadenoma 4 (6.9 por ciento), de origen farmacológico 4 (6.9 por ciento), síndrome de ovario poliquístico 3 (5.2 por ciento),macroadenoma 1 (1.7 por ciento). Recibieron inductores de ovulación. El seguimeinto promedio de las pacientes con tratamiento farmacológico fue de 19.1 meses dismunuyendo los niveles de PRL y mejoría de su disfunción ovárica. Estos resultados confirman que en pacientes con alteraciones del ciclo e infertilidad debe descartarse una hiperprolactinemia

Assuntos

RESUMO

A pigeon crop-sac bioassay for prolactin was developed applying a morphometric approach for quantification of the epithelial cell proliferation induced by the hormone. A small male dove, indigenous from South America (Zenaida auriculata) previously castrated was used as experimental animal. The total dose of prolactin was divided into 4 daily injections administered systemically into the pectoral muscles. The number of the proliferated cell layers used as the bioassay end point was analyzed statistically. This procedure yields a highly sensitive bioassay with an excellent precision index, particularly well suited for quantification of the different molecular forms of pituitary PRL.

Assuntos

RESUMO

The effect of L-DOPA on milk removal and on prolactin release during suckling or milking was studied in lactating ewes. Various doses of L-DOPA (25, 50, 100 and 200 mg per animal) were injected iv 30 min before the suckling or milking period. Control ewes were injected with 0.9% NaCl solution only. Milking induced a significant long-lasting release of prolactin. An inhibition of milk removal was obtained with the dose of 200 mg of L-DOPA. An inhibition of prolactin secretion was observed related to the dose of drug administered. The inhibitory effect of 200 mg of L-DOPA on the secretion of prolactin after milking lasted for about 120 min, and thereafter a significant increase in serum prolactin level occurred. This increase in serum prolactin was not due to a "rebound" effect of L-DOPA, since the milking stimulus had to be present to induce the delayed increase in prolactin. Doses of 25 or 50 mg of L-DOPA prevented the surge of prolactin observed immediately after milking, but a long-lasting release of prolactin was obtained thereafter. The inhibitory effect of L-DOPA on prolactin release could be overridden by the suckling or milking stimuli according to the dose administered. The suckling stimulus was more effective than milking in overriding the inhibitory effect of the low dose of L-DOPA. The results indicate that milk removal and prolactin release induced by milking or suckling in lactating ewes is inhibited by an increase in monoamines at the hypothalamic-hypophyseal level.

Assuntos

RESUMO

A pigeon crop-sac bioassay for prolactin was developed applying a morphometric approach for quantification of the epithelial cell proliferation induced by the hormone. A small male dove, indigenous from South America (Zenaida auriculata) previously castrated was used as experimental animal. The total dose of prolactin was divided into 4 daily injections administered systemically into the pectoral muscles. The number of the proliferated cell layers ysed as the bioassay end point was analyzedstatistically. This procedure yields a highly sensitive bioassay with an excellent precision index, particularly well suited for quantification of the different molecular forms of pituitary PRL (AU)

Assuntos

RESUMO

A pigeon crop-sac bioassay for prolactin was developed applying a morphometric approach for quantification of the epithelial cell proliferation induced by the hormone. A small male dove, indigenous from South America (Zenaida auriculata) previously castrated was used as experimental animal. The total dose of prolactin was divided into 4 daily injections administered systemically into the pectoral muscles. The number of the proliferated cell layers ysed as the bioassay end point was analyzedstatistically. This procedure yields a highly sensitive bioassay with an excellent precision index, particularly well suited for quantification of the different molecular forms of pituitary PRL

Assuntos