RESUMEN
Paradoxical sleep deprivation (PSD) presents different effects on metabolism and neurological functions. In addition, over long duration, sleep restriction (SR) can promote permanent changes. The prostate is an endocrine-dependent organ with homeostatic regulation directly related to hormone levels. Our study proposed to demonstrate the experimental prostatic effects of PSD (96 h), PSD with recovery (PSR - 96/96 h), and sleep restriction (SR - 30 PSD cycles/recovery). PSD and SR promoted decrease in serum testosterone and significant increase in serum and intraprostatic corticosterone. In agreement, androgen receptors (AR) were less expressed and glucocorticoid receptors (GR) were enhanced in PSR and SR. Thus, the prostate, especially under SR, demonstrates a castration-like effect due to loss of responsiveness and sensitization by androgens. SR triggered an important inflammatory response through enhancement of serum and intraprostatic pro- (IL-1α, IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines. Furthermore, the respective receptors of anti-inflammatory cytokines (IL-1RI and TNF-R) were highly expressed in the prostatic epithelium and stroma. PSR can partially restore prostate homeostasis, as it restores testosterone and the prostate proliferation index, in addition to promoting balance in the inflammatory response that is considered protective. PSD and SR are key factors in the endocrine axis that coordinate prostatic homeostasis, and significant changes in these factors have consequences on prostate functionality.
Asunto(s)
Gerbillinae , Próstata , Receptores Androgénicos , Privación de Sueño , Testosterona , Animales , Masculino , Privación de Sueño/metabolismo , Privación de Sueño/patología , Próstata/metabolismo , Próstata/patología , Testosterona/sangre , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Corticosterona/sangre , Citocinas/metabolismo , Inflamación/metabolismo , Inflamación/patología , Castración , Andrógenos/metabolismoRESUMEN
Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-ß1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-ß1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.
Asunto(s)
Factor de Crecimiento Transformador beta1 , Microambiente Tumoral , Embarazo , Femenino , Humanos , Compuestos de Bencidrilo , Carcinogénesis , FenotipoRESUMEN
The prostate is not an organ exclusive to the male. It is also found in females of several species, including humans, in which part of the Skene gland is homologous to the male prostate. Evidence is accumulating that changes in the stroma are central to tumorigenesis. Equally, telocytes, a recently discovered type of interstitial cell, are essential for the maintenance of stromal organization. However, it is still uncertain whether there are telocytes in the female prostate and if they play a role in tumorigenesis. The present study used ultrastructural and immunofluorescence techniques to investigate the presence of telocytes in the prostate of Mongolian gerbil females, a rodent model that often has a functional prostate in females, as well as to assess the impact of a combination of N-ethyl-N-nitrosourea, testosterone, and estradiol on telocytes. The results point to the presence of telocytes in the female prostate in the perialveolar and interalveolar regions, and reveal that these cells are absent in regions of benign and premalignant lesions in the gland, in which the perialveolar smooth muscle is altered. Additionally, telocytes are also closely associated with infiltrated immune cells in the stroma. Our data suggest that telocytes are important for both the maintenance of smooth muscle and prostatic epithelium integrity, which indicates a protective role against the advancement of tumorigenesis. But telocytes are also associated with immune cells and a proinflammatory/proangiogenic role for these cells cannot be ruled out, implying that telocytes have a complex role in prostatic tumorigenesis in females.
Asunto(s)
Próstata , Telocitos , Animales , Antígenos CD34/metabolismo , Carcinogénesis/metabolismo , Femenino , Gerbillinae/metabolismo , Humanos , Masculino , Próstata/metabolismo , Telocitos/metabolismoRESUMEN
Advances in prostatic stroma studies over the past few decades have demonstrated that the stroma not only supports and nourishes the gland's secretory epithelium but also participates in key aspects of morphogenesis, in the prostate's hormonal metabolism, and in the functionality of the secretory epithelium. Furthermore, the stroma is implicated in the onset and progression of prostate cancer through the formation of the so-called reactive stroma, which corresponds to a tumorigenesis-permissive microenvironment. Prostatic stromal cells are interconnected and exchange paracrine signals among themselves in a gland that is highly sensitive to endocrine hormones. There is a growing body of evidence that telocytes, recently detected interstitial cells that are also present in the prostate, are involved in stromal organization, so that their processes form a network of interconnections with both the epithelium and the other stromal cells. The present review provides an update on the different types of prostate stromal cells, their interrelationships and implications for prostate development, physiology and pathological conditions.
Asunto(s)
Próstata/patología , Células del Estroma/patología , Animales , Humanos , Masculino , Comunicación Paracrina/fisiología , Neoplasias de la Próstata/patologíaRESUMEN
The postlactational involution of the mammary gland is a complex process. It involves the collapse of the alveoli and the remodeling of the extracellular matrix, which in turn implies a complex set of interrelations between the epithelial, stromal, and extracellular matrix elements. The telocytes, a new type of CD34-positive stromal cell that differs from fibroblasts in morphological terms and gene expression, were detected in the stroma of several tissues, including the mammary gland; however, their function remains elusive. The present study employed three-dimensional reconstructions and immunohistochemical, ultrastructural, and immunofluorescence techniques in histological sections of the mammary gland of the Mongolian gerbil during lactation and postlactational involution to evaluate the presence of telocytes and to investigate a possible function for these cells. By means of immunofluorescence assays for CD34 and c-kit, major markers of telocytes, and also through morphological and ultrastructural evidences, telocytes were observed to surround the mammary ducts and collapsing alveoli. It was also found that these cells are associated with matrix metalloproteinase 9, which indicates that telocytes can play a role in extracellular matrix digestion, as well as vascular endothelial growth factor, a factor that promotes angiogenesis. Together, these data indicate that telocytes are a distinct cell type in the mammary gland and, for the first time, show that these cells possibly play a role in tissue remodeling and angiogenesis during the postlactional involution of the mammary gland.
Asunto(s)
Lactancia/metabolismo , Glándulas Mamarias Animales/fisiología , Telocitos/metabolismo , Animales , Antígenos CD34/metabolismo , Matriz Extracelular/metabolismo , Femenino , Expresión Génica/genética , Gerbillinae/metabolismo , Glándulas Mamarias Animales/metabolismo , Neovascularización Patológica/metabolismo , Células del Estroma/metabolismo , Telocitos/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Prenatal and neonatal exposure to estrogenic compounds, such as ethinylestradiol (EE), promotes a variety of developmental disorders, including malformations and alterations in the morphology of glands, such as the prostate gland. Therefore, the aim of this study was to evaluate the morphological effects of neonatal exposure to EE on prostatic tissue and on the identification and quantification of gerbil gland macrophages in adult and senile Mongolian gerbils. The animals were exposed to EE (10 µg/kg/day) and to the vehicle, mineral oil (100 µL) (control group) during the first 10 days of postnatal life (lactation period). Adult gerbils were euthanized at 120 days and senile gerbils at 12 months of age. Our findings permitted verification of the presence of areas with proliferative foci in the prostate glandular portions in the adult and senile animals exposed to EE. There was also an increase in macrophages in the prostate tissue of adult and senile gerbils; these cell types alter the stromal microenvironment and possibly modify the interactions between the epithelium and stroma. Neonatal exposure to EE changes the pattern of prostatic development, leading to alterations in the arrangement of cells, including macrophages, and may be related to the onset of proliferative disorders in the prostate of adult gerbils and during aging.
Asunto(s)
Etinilestradiol/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Próstata/efectos de los fármacos , Animales , Epitelio/metabolismo , Receptor alfa de Estrógeno/metabolismo , Estrógenos/metabolismo , Etinilestradiol/metabolismo , Femenino , Gerbillinae/metabolismo , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Receptores Androgénicos/efectos de los fármacos , Receptores Androgénicos/metabolismo , Testosterona/metabolismoRESUMEN
The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α-reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 µg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three-dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.
Asunto(s)
Finasterida/toxicidad , Gerbillinae/crecimiento & desarrollo , Próstata , Animales , Femenino , Masculino , Próstata/efectos de los fármacos , Próstata/crecimiento & desarrollo , Receptores Androgénicos/metabolismo , Testosterona/sangreRESUMEN
The prostate is a gland that is not exclusively present in males, being also found in females of several mammalian species, including humans. There is evidence that the prostate in both sexes is affected by the same pathologies such as prostatitis, benign alterations and even cancer. In view of the difficulties of manipulating the prostate gland, the Mongolian gerbil (Meriones unguiculatus), a rodent species with high incidence of functional prostates in females, is widely used in studies of the female prostate. However, despite knowing much about the similarities between the female and male prostate, little emphasis has been placed on the differences between them. This review investigates the intersex differences in prostate development, physiology and pathogenesis. The female prostate develops earlier than in males and studies indicate that it is more sensitive to oestrogens than the male prostate, as well as being more sensitive to exposure to xenoestrogens, such as Bisphenol A and methylparaben, with a higher susceptibility to benign lesions in the adult and senile prostate than in males. In addition, the female prostate is impacted by pregnancy and the oestrous cycle, and is also dependent on progesterone. The peculiarities of the female prostate raise concerns about the risk of it undergoing neglected changes as a result of environmental chemicals, since safe dosages are established exclusively for the male prostate.
RESUMEN
The prostate is an accessory reproductive gland that is sensitive to the action of exogenous compounds known as endocrine disrupters that alter normal hormonal function. Finasteride is a widely used chemical that acts to inhibit the conversion of testosterone in its most active form, dihydrotestosterone. It is known that intrauterine exposure to finasteride causes changes in the male prostate even at low dosages; however, it is not known whether these dosages are capable of causing changes in the female prostate, which is present in a large number of mammalian species, including humans. In the present study, histochemistry, immunohistochemistry, immunofluorescence, serological dosages, and three-dimensional reconstruction techniques were employed to evaluate the effects of intrauterine exposure to a low dose of finasteride (100 µg.BW/d) on postnatal prostate development in male and female Mongolian gerbils. The results indicate that the gerbil female prostate also undergoes alterations following intrauterine exposure to finasteride, exhibiting a thickening of periductal smooth muscle and increased stromal proliferation. There are also intersex differences in the impact of exposure on the expression of the androgen receptor, which was increased in males, and of the estrogen-α receptor, which was decreased in the male prostate but unchanged in females. Altogether, this study indicates there are sex differences in the effects of finasteride exposure even at low dosages.
Asunto(s)
Desarrollo Embrionario/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Finasterida/toxicidad , Genitales Femeninos/efectos de los fármacos , Gerbillinae/embriología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Próstata/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Genitales Femeninos/embriología , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Próstata/embriología , Receptores Androgénicos/metabolismo , Reproducción/efectos de los fármacos , Testosterona/metabolismoRESUMEN
Finasteride is a drug that is widely used in the treatment of benign prostatic hyperplasia, hair loss and even as a chemotherapeutic agent in the treatment of prostatic adenocarcinoma. However, its use is known to cause several side effects in adults and it can also cause changes in the embryonic development of the male prostate, which is a cause for concern given the possibility of the accumulation of finasteride in the environment. Nevertheless, no studies have investigated the effects of finasteride on the development of the prostate in females, which occurs in several species of mammals. To evaluate the effects of intrauterine exposure to finasteride (500µgkg-1 day-1) on postnatal prostate development in the Mongolian gerbil in the present study, we used immunohistochemistry, immunofluorescence, serological analysis and three-dimensional reconstruction techniques. Differences were observed in the effects of finasteride on periductal smooth muscle and cell proliferation between the sexes, as well as intersex differences in the presence of the androgen receptor, which was elevated in males, and the oestrogen receptor ERα, which was increased in females. Together, the data indicate that the female prostate has its own hormone dynamics and that there are sex-specific differences in the way in which the female prostate reacts to prenatal exposure to finasteride.
Asunto(s)
Finasterida/farmacología , Gerbillinae/crecimiento & desarrollo , Efectos Tardíos de la Exposición Prenatal , Próstata/efectos de los fármacos , Próstata/crecimiento & desarrollo , Animales , Femenino , Inmunohistoquímica , Masculino , Organogénesis/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Efectos Tardíos de la Exposición Prenatal/veterinaria , Próstata/metabolismo , Receptores Androgénicos/efectos de los fármacos , Receptores Androgénicos/metabolismo , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Caracteres SexualesRESUMEN
Telocytes are recently categorised CD34-positive interstitial cells that comprise the cells which were previously called interstitial Cajal-like cells (ICLCs). These were detected in the stroma of various organs such as the prostate, lungs, mammary glands, liver, gallbladder, and jejunum, among others. Several functions have been proposed for telocytes, such as a supportive role in smooth muscle contraction and immune function in adult organs, and tissue organisation and paracrine signalling during development, as well as others. In the jejunum, little is known about the function of telocytes in the adult organ, or is there any information about when these cells develop or if they could have an auxiliary role in the development of the jejunum. The present study employed histological, immunohistochemical and immunofluorescence techniques on histological sections of the jejunum of Mongolian gerbil pups on two different days of postnatal development of the jejunum, covering the maturation period of the organ. By immunolabelling for CD34, it was observed that telocytes are already present in the jejunum during the first week of postnatal life and exist in close association with the developing muscularis mucosae, which are therefore TGFß1-positive. The telocytes are still present at the end of the first month of life, and a portion of them present co-localisation with c-Kit. Fibroblast-like cells, which are exclusively c-Kit-positive, are also observed, which may indicate the presence of interstitial Cajal cells (ICCs). Finally, it can be hypothesised that a portion of the telocytes may give rise to ICCs, which are c-Kit-positive but CD34 negative.
Asunto(s)
Yeyuno/crecimiento & desarrollo , Telocitos/citología , Animales , Antígenos CD34/genética , Antígenos CD34/metabolismo , Diferenciación Celular , Gerbillinae , Células Intersticiales de Cajal/citología , Células Intersticiales de Cajal/metabolismo , Yeyuno/citología , Telocitos/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Chrysin is a bioflavonoid found in fruits, flowers, tea, honey and wine, which has antioxidant, anti-inflammatory, antiallergic and anticarcinogenic properties. This flavone has also been considered as beneficial for reproduction due its testosterone-boosting potential. Thus, the aim of this study was to evaluate the effects of chrysin on the prostate and gonads of male and female adult gerbils. In addition, a comparative analysis of the effects of testosterone on these same organs was conducted. Ninety-day-old male and female gerbils were treated with chrysin (50mgkg-1day-1) or testosterone cypionate (1mgkg-1week-1) for 21 days. The ventral male prostate and female prostate were dissected out for morphological, morphometric-stereological and ultrastructural assays. Testes and ovaries were submitted to morphological and morphometric---stereological analyses. Chrysin treatment caused epithelial hyperplasia and stromal remodelling of the ventral male and female prostate. Ultrastructurally, male and female prostatic epithelial cells in the chrysin group presented marked development of the organelles involved in the biosynthetic-secretory pathway, whereas cellular toxicity was observed only in female glands. Chrysin preserved normal testicular morphology and increased the number of growing ovarian follicles. Comparatively, testosterone treatment was detrimental to the prostate and gonads, since foci of prostatic intraepithelial neoplasia and gonadal degeneration were observed in both sexes. Thus, under the experimental conditions of this study, chrysin was better tolerated than testosterone in the prostate and gonads.
Asunto(s)
Anabolizantes/farmacología , Flavonoides/farmacología , Ovario/efectos de los fármacos , Próstata/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Células Epiteliales/efectos de los fármacos , Femenino , Gerbillinae , Hiperplasia/patología , Masculino , Ovario/ultraestructura , Próstata/ultraestructura , Testículo/ultraestructura , Testosterona/análogos & derivados , Testosterona/farmacologíaRESUMEN
Chrysin is a plant-derived polyphenol that has the potential to increase endogenous testosterone levels both by inhibiting the aromatase enzyme and by stimulating testicular steroidogenesis. The effects of chrysin on the prostate are unknown, especially during its development and functional maturation. Thus, the aim of this study was to evaluate the effects of chrysin prepubertal exposure on the male and female prostates of both pubertal and adult gerbils. To evaluate the possible androgenic responses of chrysin, gerbils were also exposed to testosterone. Male and female gerbils were exposed to chrysin or to testosterone cypionate from postnatal day 15 to 42. Male and female gerbils were euthanized at either 43days or 90days age. The prostates were collected for biometrical, morphological and immunohistochemical analysis. The results showed that prepubertal exposure to chrysin had differential effects on the prostate of both pubertal and adult animals. The prostates of male and female pubertal gerbils showed no histological alterations, although there was increased frequency of androgen receptor (AR) in males and females, and estrogen receptor alpha (ERα) in females. Adult males and females presented developed prostate glands, with higher cell proliferative rate. In addition, AR and ERα frequency remained high in the prostate of adult animals. These results demonstrated that prepubertal exposure to chrysin disrupts steroid receptors regulation in the prostate, potentiating the response of this gland to the biological effects of endogenous steroids. In this context, excessive consumption of phytoestrogens during the critical stages of development should be considered with caution.
Asunto(s)
Receptor alfa de Estrógeno/metabolismo , Flavonoides/farmacología , Próstata/efectos de los fármacos , Receptores Androgénicos/metabolismo , Animales , Femenino , Gerbillinae , Masculino , Próstata/metabolismo , Maduración Sexual , Testosterona/análogos & derivados , Testosterona/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Studies have shown that exposure to environmental chemicals known as endocrine disruptors can cause permanent changes in genital organs, such as the prostate. Among these environmental chemicals stands out bisphenol A (BPA). Another factor associated with prostate changes is the consumption of a high-fat diet. Although the relationship between the consumption of a high-fat diet and an increased risk of prostate cancer is well established, the mechanisms that lead to the establishment of this disease are not completely understood, nor the simultaneous action of BPA and high-fat diet. METHODS: Adult gerbils (100 days old) were divided in four groups (n = 6 per group): Control (C): animals that received a control diet and filtered water; Diet (D): animals that received a high-fat diet and filtered water; BPA: animals that received a control diet and BPA - 50 µg kg-1 day-1 in drinking water; BPA + Diet (BPA + D): animals that received a high-fat diet + BPA - 50 µg kg-1 day-1 in drinking water. After the experimental period (6 months), the dorsolateral and ventral prostate lobes were removed, and analyzed by several methods. RESULTS: Histological analysis indicated premalignant and malignant lesions in both prostatic lobes. However, animals of the D, BPA, and BPA + D groups showed a higher incidence and larger number of prostatic lesions; inflammatory foci were also common. Markers to assess prostate lesions, such as increased activation of the DNA repair system (PCNA-positive cells), androgen receptor (AR), and number of basal cells, confirmed the histology. However, serum levels of testosterone did not change under the experimental conditions. CONCLUSIONS: The results indicated that the methodology used was effective in generating metabolic changes, which directly compromised prostatic homeostasis. Diet and BPA appear to modulate the activation of the AR pathway and thereby optimize tumor establishment in the gerbil prostate.
Asunto(s)
Compuestos de Bencidrilo/efectos adversos , Dieta Alta en Grasa/efectos adversos , Fenoles/efectos adversos , Próstata , Neoplasias de la Próstata , Administración Oral , Animales , Compuestos de Bencidrilo/administración & dosificación , Carcinogénesis/inducido químicamente , Carcinogénesis/metabolismo , Modelos Animales de Enfermedad , Disruptores Endocrinos , Estrógenos no Esteroides/administración & dosificación , Estrógenos no Esteroides/efectos adversos , Gerbillinae , Masculino , Fenoles/administración & dosificación , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , TiempoRESUMEN
We employed histological techniques to assess the effects of intrauterine exposure to different dosages of E2 on male and female Mongolian gerbils on the postnatal development of the prostate. E2 promotes alterations this gland branches in the female, but not in males, even at low dosage, at higher dosages, acini of altered aspect are verified in the male and female prostate, as well as a decrease in branching number, reduced cell proliferation and staining for FGF10, simultaneously to the increased labelling for TGFß1, which may account for alterations on branching of the prostate. The sensitivity of the female prostate to intrauterine exposure to E2, which can reflect the E2 dependence of female prostate development. This becomes alarming in view of the occurrence of prostate in female of several mammals and including women, and the possibility that low E2 dosage exposures considered safe to males provoke developmental alterations in female prostate.
Asunto(s)
Estradiol/toxicidad , Estrógenos/toxicidad , Efectos Tardíos de la Exposición Prenatal , Próstata/efectos de los fármacos , Animales , Antígenos CD34/metabolismo , Estradiol/sangre , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Estrógenos/sangre , Femenino , Factor 10 de Crecimiento de Fibroblastos/metabolismo , Gerbillinae , Masculino , Intercambio Materno-Fetal , Embarazo , Próstata/metabolismo , Próstata/patología , Receptores Androgénicos/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Telocytes are CD34-positive interstitial cells, known to exert several functions, one of which is a role in tissue organisation, previously demonstrated by telocytes in the myocardium. The existence of telocytes in the prostate has recently been reported, however, there is a lack of information regarding the function of these cells in prostate tissue, and information regarding the possible role of these cells in prostatic development. This study used immunofluorescence techniques in prostate tissue and prostatic telocytes in culture to determine the relationship between telocytes and prostate morphogenesis. Furthermore, immunofluorescent labelling of telocytes was performed on prostate tissue at different stages of early postnatal development. Initially, CD34-positive cells are found at the periphery of the developing alveoli, later in the same region, c-kit-positive cells and cells positive for both factors are verified and CD34-positive cells were predominantly observed in the interalveolar stroma and the region surrounding the periductal smooth muscle. Fluorescence assays also demonstrated that telocytes secrete TGF-ß1 and are ER-Beta (ERß) positive. The results suggest that telocytes play a changing role during development, initially supporting the differentiation of periductal and perialveolar smooth muscle, and later, producing dense networks that separate alveoli groups and form a barrier between the interalveolar region and periurethral smooth muscle. We conclude that telocytes play a relevant role in prostate tissue organisation during postnatal development.
Asunto(s)
Gerbillinae/crecimiento & desarrollo , Organogénesis/genética , Próstata/citología , Telocitos/citología , Animales , Antígenos CD34/genética , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Diferenciación Celular , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Expresión Génica , Gerbillinae/genética , Gerbillinae/metabolismo , Humanos , Masculino , Cultivo Primario de Células , Próstata/crecimiento & desarrollo , Próstata/metabolismo , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/metabolismo , Telocitos/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
The effects of intrauterine exposure to 17ß-oestradiol (E2) are well studied for the male prostate and there are accumulating evidences that the exposure to high dosages leads to a hypomorphic development. However, there is a lack of information about the effects of intrauterine exposure to E2 in the prostate of rodent females, and such research becomes relevant in view of the presence of functional prostate in a proportion of women, and the morphophysiological similarities between the prostate of female rodents and the prostate of women. This study uses histochemical, immunohistochemical, immunofluorescence and three-dimensional (3D) reconstruction techniques to evaluate the effects of intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both male and female gerbils. It was verified that intrauterine exposure to E2 promotes epithelial proliferation and growth of prostatic budding in females, whereas in males the prostatic budding shows hypomorphic growth in the VMP (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together, the data demonstrate that intrauterine exposure to E2 causes different effects on male and female prostates of the gerbil even at the early postnatal development of the gland.
Asunto(s)
Estradiol/metabolismo , Estradiol/farmacología , Próstata/efectos de los fármacos , Animales , Animales Recién Nacidos/embriología , Animales Recién Nacidos/metabolismo , Disruptores Endocrinos/metabolismo , Disruptores Endocrinos/farmacología , Femenino , Gerbillinae/embriología , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , Próstata/embriología , Receptores Androgénicos/efectos de los fármacos , Receptores de Estrógenos/efectos de los fármacos , Factores SexualesRESUMEN
This study evaluated the effects of testosterone in the bulbourethral glands (BG) of the bat, Artibeus planirostris, by performing castration and posterior hormonal supplementation of the animals. The results showed a decrease in testosterone levels in animals 15days after castration, which induced a small reduction in epithelium height, percentage of AR+ cells, and an increase in the amount of basal cells. This reduction became more severe in groups castrated for longer periods (19 and 22days), where there was also an increase in apoptotic cells. Moreover, the hormonal supplementation increased testosterone levels (after 3 and 7days of supplementation), causing a glandular reactivation that increased the epithelium height and AR expression. In conclusion, BG took longer to respond to ablation of testosterone than other reproductive glands, since it showed evident aspects of regression only in animals 22days after castrated.
Asunto(s)
Glándulas Bulbouretrales , Quirópteros , Regulación de la Expresión Génica/efectos de los fármacos , Receptores Androgénicos/biosíntesis , Testosterona/farmacología , Animales , Glándulas Bulbouretrales/citología , Glándulas Bulbouretrales/metabolismo , Quirópteros/anatomía & histología , Quirópteros/metabolismo , Masculino , Técnicas de Cultivo de Órganos/métodosRESUMEN
BACKGROUND: Estrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. METHODS: We adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. RESULTS: Histopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. CONCLUSIONS: Estrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time.
Asunto(s)
Andrógenos , Estradiol , Próstata , Neoplasias de la Próstata , Andrógenos/metabolismo , Andrógenos/farmacología , Animales , Carcinogénesis/efectos de los fármacos , Carcinogénesis/patología , Carcinógenos/farmacología , Daño del ADN/efectos de los fármacos , Progresión de la Enfermedad , Células Epiteliales/patología , Estradiol/metabolismo , Estradiol/farmacología , Masculino , Metilnitrosourea/farmacología , Próstata/efectos de los fármacos , Próstata/patología , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/fisiopatología , Neoplasias de la Próstata/prevención & control , Factores Protectores , RatasRESUMEN
The female prostate is a reproductive gland that typically presents a morphology similar to that of the male gland and is highly developed in female Mongolian gerbils. Two main cell populations compose the epithelium gland: basal and secretory luminal cells. However, during postnatal development, diverse secretory cell phenotypes are distributed among the typical ones. Prostate homeostasis is under the control of sexual hormones, such as oestrogen and progesterone. After hormonal deprivation the female gland undergoes several morphophysiological changes. The objective of this study was to identify and characterise, structurally and ultrastructurally, the cellular heterogeneity of the female prostate epithelium in normal conditions and after ovariectomy. Histological routine stains, such as haematoxylin-eosin, periodic acid-Schiff and silver impregnation, as well as immunocytochemical techniques were used to enable identification of the different cell types. Some secretory cells types were identified and characterised as mucinous, basophil, clear, ciliated, droplet, spumous and neuroendocrine cells. Population tally data showed that the hormonal suppression caused by ovariectomy resulted in a decrease in the proportions of basophil and clear cells and an increase in spumous cells. Thus, the secretory epithelial cells of the female gerbil prostate are not morphologically and functionally uniform, presenting a phenotypical plasticity according to the hormonal environment in which they operate.