RESUMO
The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERß. Castration promoted an increase in the CYP19, while decreasing 17ßHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3ßHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland.
RESUMO
The prostate undergoes normal or pathological morphological changes throughout life. An understanding of these changes is fundamental for the comprehension of aging-related pathological processes such as benign prostatic hyperplasia (BPH) and cancer. In the present study, we show some of these morphological changes, as well as histochemical techniques like Weigert's resorcin-fuchsin method, Picrosirius Red, and Gömöri's reticulin for use as tools in the study of prostate tissue under light microscopy. For this purpose, prostates of the Mongolian gerbil (n = 9), an experimental model that develops BPH spontaneously, were analyzed at three life stages: young (1 month old), adult (3 months old), and old (15 months old). The results showed that fibrillar components such as collagen, and reticular and elastic fibers, change throughout life. In young animals, the prostate has cuboidal epithelium surrounded by thin layers of smooth muscle, continuous collagen fibers, winding reticular fibers, and sporadic elastic fibers. With adulthood, the epithelium becomes columnar, encircled by compacted muscle cells among slender collagen fibers, elongated reticular fibers, and linear elastic fibers. In aging individuals, the prostate's epithelium stratifies, surrounded by thick muscle layers among dense collagen fibers, disordered reticular fibers, and elastic fibers in different planes. We also identified a few accumulations of lipid droplets and lipofuscin granules in adult animals and high accumulation in old animals evidenced by Oil red O and Gömöri-Halmi techniques, respectively. The histochemical techniques presented here have been demonstrated to be useful and accessible tools in prostate studies. RESEARCH HIGHLIGHTS: Cytochemical techniques to study prostate morphology. The prostate changes with age.
Assuntos
Próstata , Hiperplasia Prostática , Masculino , Animais , Humanos , Adulto , Lactente , Próstata/patologia , Reticulina , Hiperplasia Prostática/patologia , Colágeno , Envelhecimento , Histocitoquímica , GerbillinaeRESUMO
The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate's adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus, aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging.
Assuntos
Córtex Suprarrenal , Humanos , Animais , Masculino , Gerbillinae/anatomia & histologia , Córtex Suprarrenal/metabolismo , Glândulas Suprarrenais/metabolismo , Corticosteroides/farmacologia , Hormônios/metabolismo , Envelhecimento , Esteroides/farmacologiaRESUMO
Heavy metals are elements found into the environment mainly due to anthropogenic activities. Naturally occurring and higher released doses cause disorders in the prostate, which depends on appropriate hormonal regulation, and exposure to heavy metals may impair prostate homeostasis. The current work highlighted the main mechanisms of toxicity of different environmental heavy metal contaminants, such as aluminum, arsenic, cadmium, chromium, lead, mercury, and nickel, and their impacts found in the prostate morphophysiology of murine models. The repercussions triggered by heavy metals on the prostate include hormonal imbalance and oxidative damage, leading to morphological alterations, which can vary according to the chemical properties of each element, exposure time and concentration, and age. The information of altered biological pathways and its impacts on the prostate of exposed murines are related to human outcomes being useful in the real context of human exposure.
Assuntos
Arsênio , Mercúrio , Metais Pesados , Humanos , Masculino , Camundongos , Animais , Próstata , Metais Pesados/toxicidade , Cádmio/toxicidade , Arsênio/toxicidade , Mercúrio/toxicidade , CromoRESUMO
The female prostate is associated with the urogenital system and presents homology in morphological terms with the male prostate. Due to its responsiveness to endogenous hormones, this gland is under a constant risk of developing prostatic pathologies and neoplasia when exposed to certain exogenous compounds. Bisphenol A (BPA) is an endocrine disruptor found in different plastic and resin products. Studies have emphasized the effects of perinatal exposure to this compound on different hormone-responsive organs. However, there have been few studies highlighting the influence on female prostate morphology of perinatal exposure to BPA. The objective of this study was to describe the histopathological alterations caused by perinatal exposure to BPA (50 µg/kg) and 17-ß estradiol (E2) (35 µg/kg) in the prostate of adult female gerbils. The results showed that E2 and BPA induced proliferative lesions in the female prostate and acted along similar pathways by modulating steroid receptors in the epithelium. BPA was also found to be a pro-inflammatory and pro-angiogenic agent. The impacts of both agents were marked in the prostatic stroma. An increase in the thickness of the smooth muscle layer and a decrease in AR expression were observed, but no alterations in the expression of ERα and ERß, leading to estrogenic sensitivity of the prostate. However, a peculiar response of the female prostate was to diminish the collagen frequency under BPA exposure correlated to smooth muscle layer. These data therefore indicate the development of features related to estrogenic and non-estrogenic tissue repercussions by BPA perinatally exposure in gerbil female prostate.
Assuntos
Disruptores Endócrinos , Próstata , Animais , Gravidez , Masculino , Feminino , Gerbillinae , Fenóis/toxicidade , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/metabolismoRESUMO
Ultimately, the Mongolian gerbils (Meriones unguiculatus) have acquired a relevant role in biological and biomedical experiments alongside other rodents. The use of gerbils in research has been mainly oriented to physiological and pharmacological studies, with special attention to nervous, digestive, and auditory systems as well as microbiology and parasitology. Ultimately, gerbils have also been applied for studying carcinogenesis in different organs and systems, since these animals show a natural propensity to develop spontaneous proliferative lesions, especially in steroid-responsive organs. This characteristic shed light on the reproductive aspects of this rodent model regarding morphological features in male and female individuals. This review of literature summarizes the significance of this model as an alternative to the use of inbred mice and rats in reproductive experimental research, highlighting recent findings. Gerbils have contributed to the expansion of knowledge in prostate biology in male and female individuals, providing studies related to prostatic morphogenesis and neoplasia. In the testes, spermiogenesis occurs in 15 steps, differently from other experimental models. Also, the complete maturation of the testis-epididymal complex occurs between the second and third months. Mammary gland alterations related to the estrous cycle and pregnancy were described, as well as its modulation under endogenous and exogenous estrogenic compounds. The ovaries frequently present ovarian cysts. Furthermore, this organ shows predominantly interstitial steroidogenic glands in the stroma, especially at aging. Adrenal gland shows a large size compared to other animals, presenting three distinct zones with a remarkable role in steroidogenesis.
Assuntos
Estrogênios , Reprodução , Gravidez , Masculino , Feminino , Ratos , Camundongos , Animais , Gerbillinae/fisiologia , Estrogênios/fisiologia , Próstata/fisiologia , BiologiaRESUMO
Bisphenol A (BPA) is a chemical agent which can exert detrimental effects on the male reproductive system, especially the prostate gland. In this study we described the efficacy of the dietary agent curcumin, alone or combined with piperine, to suppress the impact of BPA on the prostate. Adult gerbils were divided into nine experimental groups (n = 7 each group), regarding control (water and oil), exposed to BPA (50 µg/kg/day in water) or curcumin (100 mg/kg) and/or piperine (20 mg/kg). To evaluate the effects of the phytotherapic agents, the other groups received oral doses every two days, BPA plus curcumin (BCm), piperine (BP), and curcumin + piperine (BCmP). BPA promoted prostatic inflammation and morphological lesions in ventral and dorsolateral prostate lobes, associated with an increase in androgen receptor-positive cells and nuclear atypia, mainly in the ventral lobe. Curcumin and piperine helped to minimize these effects. BPA plus piperine or curcumin showed a reduction in nuclear atypical phenotype, indicating a beneficial effect of phytochemicals. Thus, these phytochemicals minimize the deleterious action of BPA in prostatic lobes, especially when administered in association. The protective action of curcumin and piperine consumption is associated with weight loss, anti-inflammatory potential, and control of prostate epithelial cell homeostasis.
Assuntos
Alcaloides/farmacologia , Compostos Benzidrílicos/toxicidade , Benzodioxóis/farmacologia , Curcumina/farmacologia , Fenóis/toxicidade , Compostos Fitoquímicos/farmacologia , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Neoplasias da Próstata , Animais , Carcinogênese/induzido quimicamente , Disruptores Endócrinos/toxicidade , Gerbillinae , Masculino , Próstata/efeitos dos fármacos , Próstata/patologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/patologia , Substâncias ProtetorasRESUMO
AIMS: Hormone receptors are the main markers applied for prognosis of breast cancer subtypes. Among modulators, exogenous chemical agents known as endocrine disruptors interact with certain receptors, triggering molecular pathways or increasing their expression. Bisphenol A (BPA), a xenoestrogen, interacts with several hormone receptors. Thus, our aim was to characterize the hormone receptor status in the mammary gland (MG) of aged female Mongolian gerbils exposed to BPA in pregnancy and lactation. METHODS: We evaluated the expression of receptors for estrogens (ERα and ERß), progesterone (PR), prolactin (PRL-R), HER2/ErbB2, and androgen (AR) in normal and hyperplastic mammary tissue and in carcinomas developed after BPA exposure. KEY FINDINGS: BPA-exposed MG presented increased ERα, whereas ERß, PR, and PRL-R showed lower expression. AR and HER2/ErbB2 showed similar expression in normal and hyperplastic tissue from control, vehicle, and BPA groups. Both receptors were found in cytoplasm and nucleus in BPA-induced carcinoma. We demonstrate the presence of EZH2 expression, an epigenetic and epithelial-mesenchymal transition (EMT) marker, with a high H-score in BPA-exposed MG, which was associated with poor prognosis of cancer. Co-localization of ERα and EZH2 was present in normal and carcinoma features, corroborating the installation of ERα-positive mammary cancer associated with the EMT process. Enhanced EZH2 in BPA-exposed mammary tissue could decrease ERß expression and promote tumorigenesis progress through HER2/ErbB2. SIGNIFICANCE: The present study proposes the Mongolian gerbil as an experimental model for mammary carcinogenesis studies, based on BPA disruption that triggers a phenotype of increased ERα/HER2 positivity and depletion of ERß/PR expression.
Assuntos
Envelhecimento , Compostos Benzidrílicos/efeitos adversos , Neoplasias da Mama/induzido quimicamente , Carcinogênese/induzido quimicamente , Disruptores Endócrinos/efeitos adversos , Glândulas Mamárias Animais/efeitos dos fármacos , Exposição Materna , Fenóis/efeitos adversos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Animais , Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Gerbillinae , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/metabolismoRESUMO
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
Orquiectomia/efeitos adversos , Ovariectomia/efeitos adversos , Prolactina/administração & dosagem , Próstata/efeitos dos fármacos , Próstata/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Atrofia , Feminino , Gerbillinae , Masculino , Orquiectomia/tendências , Ovariectomia/tendências , Prolactina/metabolismo , Próstata/metabolismo , Receptores da Prolactina/agonistas , Receptores da Prolactina/metabolismo , Recuperação de Função Fisiológica/fisiologiaRESUMO
BACKGROUND: The prostate is susceptible to changes in androgen levels, which can play an important role in the development of Benign Prostatic Hyperplasia (BPH). Natural compounds have beneficial properties for organisms and can be an important therapeutic strategy in the treatment of diseases. ß-Caryophyllene (BCP) is a phytocannabinoid present in several medicinal and food plants species and has shown beneficial effects in different organs. However, little is known about its effects on the prostate. The present study seeks to evaluate the effects of exposure to BCP on the morphophysiology of the ventral prostate of adult gerbils supplemented with testosterone. METHODS: Animals were distributed into four groups (n = 8/group): Intact control (C); ß-Caryophyllene (BCP): ß-Caryophyllene (50 mg/kg/day); Testosterone (T): animals received subcutaneous injections of Testosterone Cypionate (3 mg/Kg), on alternate days, for one month and were euthanized 30 days supplementation ended; Testosterone and ß-Caryophyllene (TBCP): animals were exposed to testosterone cypionate (3 mg/Kg) to induce hyperplastic alterations followed by daily BCP (50 mg/kg). Morphological, biometric, immunohistochemical, and serological analyses were performed. RESULTS: Proliferative disorders and inflammatory foci were present in the ventral prostate of all experimental groups. An increase in the multiplicity of benign intraepithelial neoplasm and subepithelial inflammatory foci was observed in T group. The incidence of intraluminal inflammatory foci and microinvasive carcinoma was verified only in the T group. Cellular rearrangement and tissue remodeling occurred in the prostate of groups exposed to phytocannabinoids. A reduction was observed in the frequency of PHH3 and Cox2 markers in the prostatic epithelium of TBCP in comparison with T. A decrease in F4/80 and CD163 positive macrophages were also observed in the prostatic stroma of the TBCP group in comparison with T. The results suggest that BCP had favorable effects on BPH, reducing the proliferation and frequency of some inflammatory cells. CONCLUSION: BCP impacts the tissue remodeling process in the premalignant prostate environment and that the use of this phytocannabinoid can have a promising effect in the handling of BPH.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Sesquiterpenos Policíclicos/administração & dosagem , Próstata/efeitos dos fármacos , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Animais , Proliferação de Células/fisiologia , Gerbillinae , Injeções Subcutâneas , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Testosterona/administração & dosagem , Testosterona/análogos & derivados , Testosterona/toxicidade , Resultado do TratamentoRESUMO
The endocrine disruptive effects caused by bisphenol A (BPA) are well known. Despite this, to date, evaluation of its long term effects is limited, meaning that there is still much to be unveiled in terms of alterations caused by perinatal exposure to BPA. Our aim was to determine if perinatal exposure to two different doses of BPA causes long term morphological and molecular alteration effects in the mammary gland (MG). We evaluated MG from Mongolian gerbil offspring exposed perinatally (during gestation and lactation) to 50 or 5000 µg/kg/day BPA. At 90 days of age the animals were subjected to a single dose of N-nitroso-N-methylurea in order to mimic a carcinogenic environment. At 6 months of age, animals in estrous were euthanized for morphological evaluation of the MGs. The MG architecture presented considerable changes in terms of detached epithelial cells, inflammation, glandular hyperplasia, and collagen fiber deposition. Furthermore, a higher index of epithelial cell proliferation was detected in comparison to the intact control group. In addition, we verified a higher molecular expression of EZH2 in the vehicle treated group, indicating that corn oil applied alone can alter the expression of this epigenetic biomarker. In conclusion, BPA perinatal exposure promotes significant changes in glandular cytoarchitecture and increases glandular epithelium proliferation rate, leading to the retention of stem-like properties. This event could compromise the fate and differentiation potential of mammary epithelium.
Assuntos
Envelhecimento/patologia , Compostos Benzidrílicos/toxicidade , Glândulas Mamárias Animais/patologia , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Actinas/metabolismo , Animais , Proliferação de Células , Colágeno/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Gerbillinae , Histonas/metabolismo , Glândulas Mamárias Animais/efeitos dos fármacos , GravidezRESUMO
Hormonal regulation controls mammary gland (MG) development. Therefore some hormone-related factors can disrupt the early phases of MGs development, making the gland more susceptible to long term modifications in its response to circulating hormones. Endocrine disruptors, such as bisphenol A (BPA), are able to cause alterations in hormone receptor expression, leading to changes in the cell proliferation index, which may expose the tissue to neoplastic alterations. Thus, we evaluated the variations in hormone receptor expression in the MG of 6-month old Mongolian gerbils exposed to BPA and 17ß estradiol during the perinatal period. Receptors for estrogen alpha (ERα), beta (ERß), progesterone (PGR), prolactin (PRL-R), and co-localization of connexin 43 (Cx43) and ERα in gerbils were analyzed, and serum concentrations of estradiol and progesterone were assessed. No alterations in body, liver, and ovary-uterus complex weights were observed. However, there was an increase in epithelial ERα expression in the 17ß estradiol (E2) group and in PGR in the BPA group. Although immunohistochemistry did not show alterations in ERß expression, western blotting revealed a decrease in this protein in the BPA group. PRL-R was more present in epithelial cells in the vehicle control (VC), E2, and BPA groups in comparison to the intact control group. Cx43 was more frequent in E2 and BPA groups, suggesting a protective response from the gland against possible malignancy. Serum concentration of estradiol reduced in VC, E2, and BPA groups, confirming that alterations also impacts steroid levels. Consequently, perinatal exposure to BPA and the reference endogenous estrogen, 17ß estradiol, are able to increase the tendency of endocrine disruption in MG in a long term manner, since repercussions are observed even 6 months after exposure.
Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Gerbillinae , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamenteRESUMO
Vegetable oils are frequently used as a vehicle in the administration of lipophilic drugs in animal tests. However, the composition of these oils may interfere with the results. One alternative to reduce this potential bias is the use of mineral oil, which is not supposed to interfere in the physiology of experimental models, since this oil is considered to be innocous. The present study shows for the first time the effects of the oral administration of corn and mineral on the prostate, demonstrating their interference in homeostasis and revealing their potential to act as endocrine disruptors. Mineral oil treatment increased the expression of AR and ERα and serum estradiol concentrations, while corn oil increased the expression of positive cells for both types of estrogen receptors. The variation in the expression of these hormone receptors resulted in morphological changes in the prostate.
Assuntos
Óleo de Milho/toxicidade , Disruptores Endócrinos/toxicidade , Óleo Mineral/toxicidade , Veículos Farmacêuticos/toxicidade , Próstata/efeitos dos fármacos , Administração Oral , Animais , Estradiol/sangue , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Gerbillinae , Homeostase/efeitos dos fármacos , Masculino , Próstata/metabolismo , Próstata/patologia , Receptores Androgênicos/metabolismo , Testosterona/sangueRESUMO
The subfamily Triatominae currently consists of 154 species, most of them being of great importance for public health because they are considered potential vectors of the protozoan Trypanosoma cruzi, the etiologic agent of Chagas disease. In addition to their epidemiological importance, these insects are considered important biological models for cell studies because they have peculiar characteristics in their cells, for example, persistence of the nucleolus during spermatogenesis. This phenomenon is characterized by the presence of the nucleolus or nucleolar corpuscles during all phases of meiosis. To date, all knowledge is restricted to the study of the presence/absence of the nucleolus during the triatomine meiosis, so the present work aimed to analyze if this persistent nucleolar material has transcriptional activity. Analysis of the meiotic metaphases of Rhodnius montenegrensis and Panstrongylus megistus by using fluorochrome acridine orange made it possible to characterize the presence of RNA in the nucleolar material. Thus, it was demonstrated, for the first time, that the persistent nucleolar material during triatomine meiosis is transcriptionally active, supporting the hypothesis of the relationship between nucleolar persistence during meiosis of these insects and the formation of the chromoid body, an organelle responsible for the support of all transcriptional activities during spermiogenesis.
Assuntos
Nucléolo Celular/genética , Meiose , Espermatogênese/genética , Transcrição Gênica , Triatominae/fisiologia , Animais , Insetos Vetores , Masculino , Reprodução/genética , Triatominae/parasitologia , Trypanosoma cruziRESUMO
Telocytes are CD34-positive cells with a fusiform cell body and long, thin cytoplasmic projections called telopodes. These cells were detected in the stroma of various organs, including the prostate. The prostate is a complex gland capable of undergoing involution due to low testosterone levels; and this condition can be reversed with testosterone replacement. Telocyte function in the mature prostate remains to be dermined, and it is not known whether telocytes can take place in tissue remodeling during prostate involution and regrowth. The present study employed structural, ultrastructural and immunohistochemical methods to investigate the telocyte's phenotypes in the ventral prostate (VP) from control (CT), castrated (CS) and testosterone replacement (TR) groups of adult male Wistar rats. Telocytes were found in the subepithelial, perimuscular and interstitical regions around glandular acini. Telocytes from CT animals have condensed chromatin and long and thin telopodes. In CS group, telocytes appeared quiescent and exhibited layers of folded up telopodes. After TR, telocytes presented loose chromatin, abundant rough endoplasmic reticulum and enlarged telopodes, closely associated with bundles of collagen fibrils. We called these cells "telocytes with a synthetic phenotype". As testosterone levels and glandular morphology returned toward to the CT group parameters, after 10 days of TR, these telocytes progressively switched to the normal phenotype. Our results demonstrate that telocytes exhibit phenotypic plasticity upon androgen manipulation and interact with fibroblast and smooth muscle cells to maintain glandular architecture in control animals and during tissue remodeling after hormonal manipulation.
Assuntos
Próstata/citologia , Telócitos/citologia , Propionato de Testosterona/administração & dosagem , Animais , Antígenos CD34/metabolismo , Masculino , Orquiectomia , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , Ratos , Ratos Wistar , Telócitos/efeitos dos fármacos , Telócitos/metabolismo , Testosterona/sangue , Propionato de Testosterona/farmacologiaRESUMO
In this study, the antifungal activity of chitosan derivatives against A. flavus was studied to understand the contribution of the molecular mass (Mw) and of the hydrophobic and electrostatic forces to the inhibition of fungal growth. The interaction of amphiphilics ranging from 8 to 130â¯kDa with model membranes of zwitterionic L-α-phosphatidylcholine (PC) and anionic L-α-phosphatidylcholine/L-α-phosphatidyl-DL-glycerol (PC:PG, 80:20â¯mol%) were exploited to obtain information on the inhibition mechanism. The results indicated that concurrent interactions control the antifungal activity. The decrease in the Mw weakens the self-association favoring the electrostatic and hydrophobic associations with the cell wall and anionic lipids of the lipid bilayer, indicating an increasing association of the amphiphilics with the fungal membrane. Laser confocal scanning microscopy of rhodamine labeled-derivatives and transmission electronic microscopy techniques showed that the amphiphilics affect the cell wall integrity by inducing the aggregation of hydrophobic constituents of the conidia.
Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Aspergillus flavus/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Antifúngicos/metabolismo , Membrana Celular/metabolismo , Quitosana/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Peso Molecular , Eletricidade EstáticaRESUMO
Glucocorticoids (GCs) are hormones that are widely used in medicine; but although side effects are generally recognised, little is known about the precise mechanisms that is implicated in many of these side effects. Furthermore, GCs are highly correlated with stress and behaviour disorders. This study evaluated the effects of the glucocorticoid corticosterone on the ventral prostate of the Mongolian gerbil. Male gerbils (Meriones unguiculatus) (n = 5) received intraperitoneal injections of saline or corticosterone in doses of 0.5 mg/kg/day and 1.5 mg/kg/day for 5 days; while some of the animals were killed immediately after the treatment, the others were killed 5 days after the treatment period. The data show that corticosterone influences the structure and functionality of this organ. This hormone has anti-proliferative and anti-apoptotic properties in the prostate. In addition, the frequencies of the androgen (AR), oestrogen (ERα, ERß) and glucocorticoid (GR) receptors changed. The frequencies of AR, GR and ERß decreased in the Ct1/5 group; in the groups with rest period, the frequencies of GR increased and ERß decreased in the epithelium. Changes in the proliferative index, apoptotic index and receptor activity may have contributed to the emergence of prostatic morphological alterations, such as the presence of cellular debris and inflammatory cells. Different doses of corticosterone had variable effects on the prostate, with a higher dose showing subtler effects and a lower dose showing more striking effects. The corticosterone effects on nuclear receptors were reverted or attenuated after a rest period, which was not observed for proliferation and apoptosis. In summary, we have demonstrated that corticosterone might influence the prostatic morphophysiology and that these changes may be linked in some way to the altered receptor distribution.
Assuntos
Corticosterona/farmacologia , Próstata/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Corticosterona/administração & dosagem , Corticosterona/sangue , Relação Dose-Resposta a Droga , Gerbillinae , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Glucocorticoides/metabolismo , Testosterona/sangueRESUMO
The prostate is a mammalian gland that shows a complex process of organogenesis. Here, a morphological study to characterize the organogenesis of the ventral prostate lobe in male gerbils was conducted. The urogenital sinus (UGS) was dissected out and processed for paraffin embedding. Histological sections were subjected to cytochemical, immunofluorescence, immunohistochemical, and three-dimensional reconstruction techniques. We found that the first ventral buds emerged from the ventral urethral epithelium between the days 20 and 21 of prenatal life, reaching the ventral mesenchymal pad and initiating the branching process on the first day of postnatal life. The buds presented a V-shaped elongation, suggesting that the smooth muscle layer (SML) plays an important role during budding events. Indeed, whereas the androgen receptor (AR) was preferentially found in the UGS mesenchyme (UGM), estrogen receptor alpha (ERα) was localized in both the UGM and in the emerging buds. This study characterized the morphological aspects of the budding process in a different rodent from rat and mice, serving as a new model for future studies on developmental biology of the prostate.
Assuntos
Gerbillinae/embriologia , Organogênese , Próstata/embriologia , Animais , Receptor alfa de Estrogênio/fisiologia , Imunofluorescência , Masculino , Microscopia , Receptores Androgênicos/fisiologiaRESUMO
The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol + testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol + testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric-estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol + testosterone. However, these hormones were not able to re-establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER-α, ER-ß, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones.
Assuntos
Androgênios/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Gerbillinae/anatomia & histologia , Próstata/efeitos dos fármacos , Testosterona/farmacologia , Animais , Feminino , Histocitoquímica , Humanos , Imuno-Histoquímica , Masculino , Próstata/anatomia & histologia , Próstata/citologiaRESUMO
The female organs, which are regulated by steroid hormones, are targets of studies especially those related to senescence. However, although the female prostate is an organ influenced by hormones and susceptible to lesions, there is still little information about its histopathology. Thus, given the morphophysiological similarity between the prostate in women and female gerbils, the present study aimed to identify the spontaneous histopathological changes in this rodent to provide contributions to the understanding of lesions that also affect the human female prostate. The structural, ultrastructural, immunohistochemical, morphometric-stereological and serological aspects, as well as the quantification of the incidence, multiplicity and percentage of acini affected by different lesions were analyzed. Benign prostate lesions including hyperplasia, prostatitis, microcalculi and calculi; preneoplastic lesions like dysplasias; premalignant lesions, such as high grade prostatic intraepithelial neoplasia as well as malignant ones, specifically adenocarcinoma, were identified in the adult gland, but they were intensified during senescence, which is possibly due to the imbalance among steroid hormone levels. Although clinical attention focuses on other urogenital organs, the real condition of the histopathological injuries in the human female prostate should be considered. A serious preventive work regarding the female prostate could be applied in the gynaecological context in order to monitor the gland and avoid possible disturbances to women's health and consequently provide better quality of life.