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.
Assuntos
Córtex Suprarrenal , Androgênios , Proliferação de Células , Gerbillinae , Testosterona , Animais , Masculino , Testosterona/farmacologia , Testosterona/metabolismo , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Androgênios/farmacologia , Androgênios/metabolismo , Proliferação de Células/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Orquiectomia , Esteroide 17-alfa-Hidroxilase/metabolismo , Aromatase/metabolismo , Morte Celular/efeitos dos fármacosRESUMO
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 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
The presence of the prostate in female mammals has long been known. However, pieces of information related to its development are still lacking. The aim of this study was to explore the budding dynamic during the initial prostate development in female gerbils. Pregnant females were timed, the fetuses were euthanized, and the urogenital sinus was dissected out between the embryonic days 20 and 24 (E20-E24 groups). Newborn pups (1-day-old; P1 group) underwent the same procedures. The female prostate development was based on epithelial buds which arose far from the paraurethral mesenchyme (PAM). The epithelial buds reached the PAM at prenatal day 24, crossing a small gap in the smooth muscle layer between the periurethral mesenchyme (PEM) and the PAM. Steroid nuclear receptors such as the androgen receptor and estrogen receptor alpha were localized in the PEM through the urethral wall, although some epithelial labeling was also present in the urogenital sinus epithelium (UGE). P63-positive cells were found only in the UGE, becoming restricted to the basal compartment after the 23rd prenatal day. The results showed that the gerbil female prostate exhibits a distinct budding pattern as compared to the male prostate development.
Assuntos
Próstata , Sistema Urogenital , Animais , Epitélio , Feminino , Gerbillinae , Humanos , Recém-Nascido , Masculino , Mesoderma , GravidezRESUMO
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
OBJECTIVE: In the present study, the in vitro and in vivo effect of the hydroalcoholic extract of Neolentinus ponderosus (EHNP) on L3 larvae of Haemonchus contortus was evaluated. MATERIAL AND METHODS: The N. ponderosus fungus was cultivated in potato dextrose liquid medium for 7 days at 120 rpm and 25 °C. Subsequently, the EHNP was obtained; in vitro bioassays were performed in 96-well plates. Furthermore, an in vitro confrontation with different concentrations of EHNP was carried out at 72 h against L3 larvae of H. contortus. The controls used were distilled water and ivermectin at 5 mg/mL. Subsequently, the in vivo activity of EHNP was evaluated using the gerbil against H. contortus L3 larvae as an experimental model. The experimental design consisted of four groups with: (1) distilled water, (2) fenbendazole at 20 mg/kg of body weight, (3) EHNP at a dose of 81 µg/mL, and (4) EHNP at a dose of 40 µg/mL. RESULTS: In vitro study showed 97% mortality of the parasite H. contortus at a concentration of 3.4 mg/mL and a lethal concentration (LC90) of 2 mg/mL EHNP. In the in vivo assessment the highest mortality was (49%) at 72 h at a concentration of 81 µg/mL bw. CONCLUSION: The result of the present study shows that EHNP has nematicidal activity in vitro and in vivo tests (close to 97% and 50%, respectively), the fungus N. ponderosus should be considered in future tests to elucidate the secondary metabolites through spectroscopic studies.
Assuntos
Agaricales , Hemoncose , Haemonchus , Doenças dos Ovinos , Animais , Basidiomycota , Hemoncose/tratamento farmacológico , Hemoncose/veterinária , Larva , Extratos Vegetais/farmacologia , OvinosRESUMO
Morphophysiological changes of the female prostate during pregnancy are still little known. Considering that this gland is highly influenced by steroid hormones, the aim of this study was to evaluate the impact of the pregnancy on female prostate morphophysiology in gerbils. Pregnant females were timed, and the prostates were analyzed at pregnancy days 6 (P6), 12 (P12), 18 (P18), and 24 (P24). Virgin females were used as the control group (C). We observed a profound change in the hormonal profile during gestation, which was marked by a high oscillation of the progesterone (P4) hormone. P4 serum levels increased, peaking at the middle of gestation, and decreased to the end of the pregnancy. The morphology of the gland in pregnant females also changed, being marked by an increase of acini lumen, and a decrease in stroma. Indeed, the acinar changes during pregnancy were followed by a significant reduction of the epithelial height, besides a change of the smooth muscle cells' morphology that became more relaxed. The number of progesterone receptor (PR) and androgen receptor (AR)-positives cells decreased with the increase of progesterone serum levels, showing an inverse relationship. Finally, we observed a reduction of epithelial proliferation and a significant increase of gland PAS-positive secretion at the end of pregnancy. Altogether, these results showed, for the first time, that the female prostate morphophysioloy is profoundly influenced by the gestational period, suggesting that the fluctuation of the P4 serum levels is the main factor influencing the gland during this period.
Assuntos
Células Epiteliais/fisiologia , Glândulas Exócrinas/fisiologia , Próstata/fisiologia , Animais , Biomarcadores/sangue , Proliferação de Células , Células Epiteliais/metabolismo , Glândulas Exócrinas/citologia , Glândulas Exócrinas/metabolismo , Feminino , Gerbillinae , Masculino , Gravidez , Progesterona/sangue , Antígeno Nuclear de Célula em Proliferação/metabolismo , Próstata/citologia , Próstata/metabolismo , Antígeno Prostático Específico/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Progesterona/metabolismo , Células Estromais/metabolismo , Células Estromais/fisiologia , Fatores de TempoRESUMO
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.
Assuntos
Lactação/metabolismo , Glândulas Mamárias Animais/fisiologia , Telócitos/metabolismo , Animais , Antígenos CD34/metabolismo , Matriz Extracelular/metabolismo , Feminino , Expressão Gênica/genética , Gerbillinae/metabolismo , Glândulas Mamárias Animais/metabolismo , Neovascularização Patológica/metabolismo , Células Estromais/metabolismo , Telócitos/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
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.
Assuntos
Finasterida/toxicidade , Gerbillinae/crescimento & desenvolvimento , Próstata , Animais , Feminino , Masculino , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Receptores Androgênicos/metabolismo , Testosterona/sangueRESUMO
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.