Expression and function of fibroblast growth factor 10 and its receptor, fibroblast growth factor receptor 213, in bovine follicles

Some fibroblast growth factors (FGFs) affect ovarian follicle cell growth and/or differentiation. Whereas many FGFs activate several FGF receptors, FGF7 and FGF10 primarily activate only one, FGFR2B. As FGF7 is produced by bovine theca cells and acts on granulosa cells, we tested the hypothesis that FGF10 may also play a role in folliculogenesis in cattle. Reverse transcription-polymerase chain reaction demonstrated the presence of FGF10 mRNA in the oocytes and theca cells of the antral follicles, as well as in the preantral follicles. FGF10 protein was detected by immunohistochemistry in the oocytes of the preantral and antral follicles, and in the granulosa and theca cells of the antral follicles. FGF10 expression in theca cells changed during follicle development; mRNA abundance decreased with increasing follicular estradiol concentration in healthy follicles, and was lowest in highly atretic follicles. Culturing of granulosa cells in serum-free medium revealed FSH regulation of FGF10 receptor expression. The addition of FGF10 to cultured granulosa cells decreased the level of estradiol but did not alter cell proliferation. These data support a role for FGF10 in signaling to granulosa cells from theca cells and/or the oocyte.

Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) gamma Activators and Pan-PPAR Partial Agonists

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

Androgen receptor in the Mongolian gerbil ventral prostate: Evaluation during different phases of postnatal development and following androgen blockage

The normal growth, differentiation and maintenance of the morphofunctional integrity of the prostate gland are dependent on the interaction of constant levels of androgens with their receptors. The need to study the responses to hormones under several conditions and the effect of their blockage is due to the fact that the human prostate is the site of a great number of age-related diseases, and the ones with a major medical importance are prostate cancer (Cap) and benign prostatic hyperplasia (BPH), which can both be treated with androgen suppression. Seventy-five male gerbils were divided, randomly, into 3 groups of 25 animals each, where each group corresponded to one phase of postnatal development. In each phase, it was possible to morphologically and stereologically analyze the compartments of prostatic ventral lobe, as well as to immunohistochemically analyze the degree of expression of androgen receptors (ARs) after the androgen blockage therapies. In addition, it was possible to establish the hormonal dosage of serum testosterone levels given the comparative approach of the expression of androgen receptors. There is a pattern of AR distribution in the prostatic ventral lobe throughout postnatal development, in which the younger the animal is the higher, the interaction of circulating androgens that stimulate the AR expression in both the epithelial and stromal compartments. The androgen blockage therapies decreased AR expression in the prostatic compartments, but the androgen reposition after these blockages was not sufficient to recover the glandular structure or stimulate the AR expression up to normal physiological conditions. Both the regulation and distribution of androgen receptors along the gerbil prostatic tissues are complex mechanisms that are likely to be genetically regulated by androgens prenatally or by other factors that are still unknown. This rodent species seems to be a valuable model in the attempt to improve the understanding of the morphophysiological and pathological behavior of this important gland in humans throughout aging and to stimulate new therapeutic ideas to fight prostate cancer. (C) 2008 Elsevier Ltd. All rights reserved.

Increased Androgen Receptor and Remodeling in the Prostatic Stroma After the Inhibition of 5-Alpha Reductase and Aromatase in Gerbil Ventral Prostate

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

5-HT2A serotoninergic receptor in the locus coeruleus participates in the first phase of lipopolysaccharide-induced fever

This study was aimed at testing the hypothesis that serotoninergic receptors in the locus coeruleus (LC) play a role in bacterial lipopolysaccharide-induced fever. To this end, 5-HT1A (WAY-100635; 3 mu g/100 nL) and 5-HT2A (ketanserin; 2 mu g/100 nL) antagonists were microinjected into the LC and body temperature was monitored by biotelemetry. Intra-LC microinjections of ketanserin or WAY-100635 caused no change in body temperature of euthermic animals. 5-HT2A antagonism abolished the first phase of the lipopolysaccharide-induced fever. Taken together, these results indicate that serotonin acting on 5-HT2A receptors in the LC mediates the first phase of the febrile response, whereas 5-HT1A receptors are not involved in the lipopolysaccharide-induced fever.

Swimming training exacerbates pathological cardiac hypertrophy in kinin B(2) receptor-deficient mice

Kallikrein-kinin system exerts cardioprotective effects against pathological hypertrophy. These effects are modulated mainly via B(2) receptor activation. Chronic physical exercise can induce physiological cardiac hypertrophy characterized by normal organization of cardiac structure. Therefore, the aim of this work was to verify the influence of kinin B(2) receptor deletion on physiological hypertrophy to exercise stimulus. Animals were submitted to swimming practice for 5 min or for 60 min, 5 days a week, during 1 month and several cardiac parameters were evaluated. Results showed no significantly difference in heart weight between both groups, however an increased left ventricle weight and myocyte diameter were observed after the 60 min swimming protocol, which was more pronounced in B(2)(-/-) mice. In addition, sedentary B(2)(-/-) animals presented higher left ventricle mass when compared to wild-type (WT) mice. An increase in capillary density was observed in exercised animals, however the effect was less pronounced in B(2)(-/-) mice. Collagen, a marker of pathological hypertrophy, was increased in B(2)(-/-) mice submitted to swimming protocol, as well as left ventricular thickness, suggesting that these animals do not respond with physiological hypertrophy for this kind of exercise. In conclusion, our data suggest an important role for the kinin B(2) receptor in physiological cardiac hypertrophy. (c) 2007 Elsevier B.V. All rights reserved.

Selective Ablation of the Androgen Receptor in Mouse Sertoli Cells Affects Sertoli Cell Maturation, Barrier Formation and Cytoskeletal Development

The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.