Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate

Prostatic differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Dihydrotestosterone, which is synthesized from testosterone by 5alpha-reductase (5alpha-r), is the active molecule triggering androgen action within the prostate. In the present work, we examined the effects of 5alpha-reductase inhibition by finasteride in the ventral prostate (VP) of the adult gerbil, employing histochemical and electron microscopy techniques to demonstrate the morphological and organizational changes of the organ. After 10 days of finasteride treatment at a dose of 100 mg/kg/day, the prostatic complex (VP and dorsolateral prostate) absolute weight was reduced to about 18%. The epithelial cells became short and cuboidal, with less secretory blebs and reduced acid phosphatase activity. The luminal sectional area diminished, suggestive of decreased secretory activity. The stromal/epithelial ratio increased, the stroma becoming thicker but less cellular. There was a striking accumulation of collagen fibrils, which was accompanied by an increase in deposits of amorphous granular material adjacent to the basal lamina and in the clefts between smooth muscle cells (SMC). Additionally, the periacinar smooth muscle became loosely packed. Some SMC were atrophic and showed a denser array of the cytoskeleton, whereas other SMC had a highly irregular outline with numerous spine-like projections. The present data indicate that 5alpha-r inhibition causes epithelial and stromal changes by affecting intra-prostatic hormone levels. These alterations are probably the result of an imbalance of the homeostatic interaction between the epithelium and the underlying stroma.

Cellular changes in the prostatic stroma of glucocorticoid-treated rats

Glucocorticoid hormones (GCs) have been widely used for the treatment of prostate cancer because of their inhibitory property against tumour growth. However, their mechanism of action in the prostate has received little attention. Excess GCs can lead to peripheral insulin resistance resulting in hyperglycaemia and hyperinsulinaemia. Insulin plays an important role as a cellular stimulant and high levels are related to low levels of androgens. Our objective has been to describe the effects of insulin resistance induced by dexamethasone treatment on the morphology of rat ventral prostate. Mate adult Wistar rats received daily intraperitoneal injections of dexamethasone or saline for five consecutive days after which the rats were killed and the ventral prostate was removed, weighed and prepared for conventional and transmission electron microscopy (TEM). Dexamethasone treatment resulted in atrophy and decreased proliferative activity of prostatic epithelial cells. TEM analysis revealed changes in the epithelium-stroma interface, with some interruptions in the basement membrane. Fibroblasts showed a secretory phenotype with dilated endoplasmic reticulum. Smooth muscle cells exhibited a contractile pattern with 50% atrophy, an irregular membrane and twisted nuclei. Mitochondrial alterations, such as enlarged size and high electron density in the mitochondrial matrix, were also detected in smooth muscle cells. Insulin resistance induced by dexamethasone is thus associated with epithelial atrophy similar to that described for diabetic rats. However, GCs are responsible for morphological changes in the stromal cell population suggesting the activation of fibroblasts and atrophy of the smooth muscle cells.

Antiestrogen therapies affect tissue homeostasis of the gerbil (Meriones unguiculatus) female prostate and ovaries

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Hormonal Oscillations During the Estrous Cycle Influence the Morphophysiology of the Gerbil (Meriones unguiculatus) Female Prostate (Skene Paraurethral Glands)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Short-term stromal alterations in the rat ventral prostate following alloxan-induced diabetes and the influence of insulin replacement

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Oestrogen supplementation following castration promotes stromal remodelling and histopathological alterations in the Mongolian gerbil ventral prostate

The effect of oestradiol on the intact and castrated adult gerbil prostate was evaluated by focussing on stromal and epithelial disorders, and hormonal receptor immunoreactivity. The experimental animals were studied by histological, histochemical and immunohistochemical techniques, morphometric-stereological analysis and transmission electron microscopy. Epithelial alterations in the oestradiol-treated animals were frequent, with an increase in epithelial cell height, areas of intense dysplasia and hyperplasia and formation of prostatic intraepithelial neoplasia (PIN). Another aspect that did not depend on the presence of testosterone was the arrangement of the fibrillar and non-fibrillar elements of the extracellular matrix among smooth muscle cells (SMC), suggesting a possible role of these cells in rearrangement and synthesis of these components, after oestrogenic treatment. In the castrated animals, an accumulation of extracellular matrix elements under the epithelium was evident, while in the intact animals the same compounds were dispersed and scarce. In the groups of intact and castrated animals, SMC and fibroblasts exhibited a secretory phenotype, which was accentuated after oestradiol administration. There was an increase of the immunoreactivity to alpha-oestrogen and androgen receptors in hyperplastic areas compared to normal epithelium, revealing the involvement of these steroid receptors in the hyperplasia and PIN development.

Matrix metalloproteinase (MMP)-2 and MMP-9 activity and localization during ventral prostate atrophy and regrowth

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Long-term inhibition of 5-alpha reductase and aromatase changes the cellular and extracellular compartments in gerbil ventral prostate at different postnatal ages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

High fat-induced obesity associated with insulin-resistance increases FGF-2 content and causes stromal hyperplasia in rat ventral prostate

Obesity affects sex hormone secretion, which can negatively influence prostatic structure, homeostasis, and disease. This investigation aimed to evaluate the repercussions of obesity induced by a high-fat diet on the rat prostate, with or without treatment with the aromatase inhibitor, Letrozole. Adult Wistar rats were fed a high-fat diet (20% saturated fat, O) for 15 weeks to induce obesity or received a balanced diet (4% fat, C). Then, a group of C and O rats were daily treated with Letrozole (1 mg/kg b.w. per day) for 2 weeks (CL and OL, respectively). Subsequently, ventral prostate was processed for analysis by transmission electron microscopy, immunohistochemistry, and Western blotting. Obesity decreased 70% of the testosterone plasma level. The prostate showed epithelial atrophy and dilated acini in the intermediate portion and epithelial wrinkling in the distal tips. The relative frequency of smooth muscle alpha-actin in the O group increased by 67%. Ultrastructurally, epithelial cells in obese animals presented altered secretory organelles, lipid droplets, and thicker subjacent fibromuscular layer. Letrozole treatment caused a partial restoration of the prostatic changes caused by obesity. Obesity increased the prostatic content of fibroblast growth factor-2 (FGF-2) by 150%, and Letrozole treatment increased this protein even more in the control and obese groups. This investigation shows that obesity provokes structural and ultrastructural changes in the epithelium of rat prostate; these changes might affect gland homeostasis and physiology. The epithelial and smooth muscle cell hyperplasia and increased FGF-2 expression observed in this experimental model of obesity/insulin-resistance might explain the high frequency of benign prostatic hyperplasia in insulin-resistant men.

Lobe identity in the Mongolian gerbil prostatic complex: A new rodent model for prostate study

Knowledge of structural and physiological differences among the prostatic lobes (PL) is the basis for development of experimental studies in traditional laboratory rodents. Although Mongolian gerbil reproductive organs have been increasingly investigated, its prostate structure is far from being properly known, and investigations of this organ focused on the ventral lobe (VL). Thus, the present study provides a thorough morphological description of prostatic complex in the male adult gerbil on the basis of topographic, histological, and ultrastructural analysis and ductal branching. Like other rodents, four pairs of PL were observed. However, in contrast to the rat and mouse, the VL is the least voluminous component and the dorsolateral lobe (DLL) is the most prominent and spatially isolated from remaining PL. The occurrence of a dorsal lobe (DL), hidden between bladder and insertion of seminal vesicles, has not been mentioned in previous reports with Mongolian gerbil. Collagenase digestion followed by microdissection revealed that, except for DL, which has a tubularacinar organization, all PL exhibit tubular organization and variable ductal branching. Distinct histological and ultrastructural features such as secretory epithelium, aspect of luminal secretion and stromal organization are reported for each PL and are confirmed by morphometric and stereological methods. Histological sections showed at least three intralobar segments in VL and DL. Ultrastructural analysis evidenced that, although luminal epithelial cells of PL share typical features of exocrine secretory cells, there are striking lobe phenotypical variations. Both merocrine and apocrine pathways are observed in variable rates in all PL, with the predominance of the former in the DLL and the latter in the CG. The morphological observations presented herein point to distinct structural identities for each PL, which probably reflects,specific functional compromise of seminal fluid secretion. These data also point to the gerbil as a good model for investigations concerning the regulation of prostate development and homeostasis, mainly with regard to the dorsal and dorsolateral PL.

Morphology of Richards' Gland in the Wasp Metapolybia docilis

Richards gland in the epiponine wasp Metapolybia docilis occurs at the anterior side of the 5(th) abdominal sternite, and is formed by approx. 360 secretory cells. The cells discharge their secretory products through accompanying duct cells into a reservoir that is formed by the invaginated intersegmental membrane between the 4(th) and 5(th) sternites. The ultrastructural characteristics of the secretory cells are indicative for the production of a non-proteinaceous secretion, which is in line with the trail substance that is used by these wasps during their swarm-founding.

Inflorescence and floral development of Dahlstedtia species (Leguminosae: Papilionoideae: Millettieae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudos de microscopia óptica e de microscopia eletrônica de varredura em folhas de Mentha spicata e de Mentha spicata x suaveolens (Lamiaceae)

O presente trabalho tem como objetivo realizar um estudo de anatomia foliar por meio de microscopia óptica e de microscopia eletrônica de varredura em Mentha spicata L. e Mentha spicata X suaveolens, caracterizando histologicamente a lâmina foliar. Secções transversais e paradérmicas da região mediana do limbo foliar mostraram a presença de epiderme unisseriada, coberta por uma fina camada de cutícula, apresentando tricomas glandulares do tipo capitado e peltado e não glandulares unisseriados multicelulares, não ramificados. O mesofilo de ambas as espécies é dorsiventral, com parênquima paliçádico uniestratificado, com células alongadas e rico em inclusões citoplasmáticas. O parênquima lacunoso é formado por três a quatro camadas de células irregulares. Os tricomas capitados presentes são classificados como do tipo I, e apresentam-se com uma célula basal, uma célula peduncular e uma grande célula apical, cujo formato varia de circular a piriforme. Os tricomas peltados consistem de uma célula basal, uma célula peduncular curta, larga e unicelular, com paredes externas cutinizadas e uma cabeça grande multicelular com 12 células secretoras, distribuídas radialmente em dois círculos concêntricos, o central com 4 células e o externo com 8 células, as quais acumulam o produto da secreção em uma cavidade entre a cutícula e as células secretoras; o pé do tricoma glandular está inserido em 11 células epidérmicas. Há predominância de tricomas capitados em relação aos tricomas peltados em ambas as espécies de Mentha.

Effect of estrogen therapy, soy isoflavones, and the combination therapy on the submandibular gland of ovariectomized rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of consumption of probiotics on presence of enterobacteria in the oral cavity

Clinical benefits of probiotics have been clearly reported in different gastrointestinal disorders, many of them caused by enterobacteria. The oral cavity is a port of entry and can be an important reservoir of these microorganisms. This work evaluated whether consumption of probiotics was able to influence the presence of enterobacteria in the oral cavity and the specific secretory response against these microorganisms. Saliva samples of healthy individuals were collected and plated in Mac-Conkey agar. Carriers of Gram-negative, rod-shaped microorganisms in the oral cavity were selected and instructed to use the probiotic Yakult LB for 20 days. Saliva was then collected and enterobacteria species were identified using the API 20 E system and by ELISA using anti-enterobacteria IgA. The results showed reduction in the prevalence of enterobacteria, but no significant changes in enterobacterial counts (log CFU/mL; p = 0.3457). The species most frequently isolated were Enterobacter cloacae and Klebsiella oxytoca, both before and after probiotic consumption. No significant changes were observed in anti-enterobacteria IgA levels. In conclusion, probiotic consumption had some influence on enterobacterial presence in the oral cavity, but did not affect enterobacterial counts or the specific immune secretory response against them.