Testosterone stimulates growth and secretory activity of the female prostate in the adult gerbil (Meriones unguiculatus)

The prostate of the female gerbil (Meriones unguiculatus) is similar to the human female prostate (Skene gland) and, despite its reduced size, it is functional and shows secretory activity. However, virtually nothing is known about its physiological regulation. This study was thus undertaken to evaluate the behavior of the gerbil female prostate in a hyperandrogenic condition. Adult females received subcutaneous injections of testosterone cypionate (1 mg/kg body weight every 48 h) up to 21 days. Circulating levels of testosterone and estradiol were monitored, and the prostate and ovaries subjected to structural and immunocytochemical analyses. The treatment resulted in sustained high levels of circulating testosterone, and caused a transient increase in estradiol. There was an increase in epithelial cell proliferation accompanied by significant reorganization of the epithelium and an apparent reduction in secretory activity, followed by a progressive increase in luminal volume density and accumulation of secretory products. Immunocytochemistry identified the expression of androgen receptor and a prostate-specific antigen (PSA)-related antigen in prostatic epithelial cells. A circulating PSA-related antigen was also found, and its concentration showed strong negative correlation with circulating estrogen. Epithelial dysplasia was detected in the prostate of treated females. Analysis of the ovaries showed the occurrence of a polycystic condition and stromal cell hyperplasia. The results indicate that testosterone has a stimulatory effect on the female prostate, inducing epithelial cell proliferation, differentiation, secretory activity, and dysplasia. The results also suggest that prostatic growth and activity, polycystic ovaries, and ovarian stromal cell hyperplasia are related to a hyperandrogenic condition in females.

Central interaction between atrial natriuretic peptide and angiotensin II in the control of sodium intake and excretion in female rats

We investigated the effects of estrogen on sodium intake and excretion induced by angiotensin II (ANG II), atrial natriuretic peptide (ANP) or ANG II plus ANP injected into the median preoptic nucleus (MnPO). Female Holtzman rats weighing 250-300 g were used. Sodium ingestion and excretion 120 min after the injection of 0.5 mu l of 0.15 M NaCl into the MnPO were 0.3 +/- 0.1 ml (N = 12) and 29 +/- 7 mu Eq in intact rats, 0.5 +/- 0.2 ml (N = 10) and 27 +/- 6 mu Eq in ovariectomized rats, and 0.2 +/- 0.08 (N = 11) and 38 +/- 8 mu Eq in estrogen-treated ovariectomized (50 mu g/day for 21 days) rats, respectively. ANG II (21 mu M) injection in intact, ovariectomized, and estrogen-treated ovariectomized rats increased sodium intake (3.8 +/- 0.4, 1.8 +/- 0.3 and 1.2 +/- 0.2 ml/120 min, respectively) (N = 11) and increased sodium excretion (166 +/- 18, 82 +/- 22 and 86 +/- 12 mu Eq/120 min, respectively) (N = 11). ANP (65 mu M) injection in intact (N = 11), ovariectomized(N = 10)and estrogen-treated ovariectomized (N = 10) rats increased sodium intake (1.4 +/- 0.2, 1.8 +/- 0.3, and 1.7 +/- 0.3 ml/120 min, respectively) and sodium excretion (178 +/- 19, 187 +/- 9, and 232 +/- 29 mu Eq/120 min, respectively). Concomitant injection of ANG II and ANP into the MnPO of intact (N = 12), ovariectomized (N = 10) and estrogentreated ovariectomized (N = 10) rats caused smaller effects than those produced by each peptide given alone: 1.3 +/- 0.2, 0.9 +/- 0.2 and 0.3 +/- 0.1 ml/120 min for sodium intake, respectively, and 86 +/- 9, 58 +/- 7, and 22 +/- 4 mu Eq/120 min for sodium excretion, respectively. Taken together, these results demonstrate that there is an antagonistic interaction of ANP and ANG II on sodium intake and excretion, and that reproductive hormones affect this interaction.

Effect of 17 beta-estradiol and alendronate on the removal torque of osseointegrated titanium implants in ovariectomized rats

Background: This study investigated the influence of estrogen deficiency and its treatment with estrogen and alendronate on the removal torque of osseointegrated titanium implants.Methods: Fifty-eight female Wistar rats received a titanium implant in the tibia metaphysis. After 60 days, which was needed for implant osseointegration, the animals were randomly divided into five groups: control (CTLE; N = 10), sham surgery (SHAM; N = 12), ovariectomy (OVX; N = 12), ovariectomy followed by hormone replacement (EST; N = 12), and ovariectomy followed by treatment with alendronate (ALE; N = 12). The CTLE group was sacrificed to confirm osseointegration, whereas the remaining groups were submitted to sham surgery or ovariectomy according to their designations. After 90 days, these animals were also sacrificed. Densitometry of femur and lumbar vertebrae was performed by dual-energy x-ray absorptiometry (DXA) to confirm systemic impairment of the animals. All implants were subjected to removal torque.Results: Densitometric analysis of the femur and lumbar vertebrae confirmed a systemic impairment of the animals, disclosing lower values of bone mineral density for OVX. Analysis of the removal torque of the implants showed statistically lower values (P <0.05) for the OVX group in relation to the other groups. However, the group treated with alendronate (ALE group) presented significantly higher torque values compared to the others.Conclusion: According to this study, estrogen deficiency was observed to have a negative influence on the removal torque of osseointegrated implants, whereas treatment with alendronate

Tissue remodeling in Guinea pig lateral prostate at different ages after estradiol treatment

Estrogen seems to have an essential role in the fibromuscular growth characteristic of benign prostatic hyperplasia (BPH). This paper describes the effects of chronic estradiol treatment on Guinea pig prostatic stroma at different ages. Tissues from experimental animals were studied by histological and histochemical procedures, morphometric-stereological analysis and transmission electron microscopy (TEM). Marked fibromuscular hypertrophy was observed after estradiol treatment in animals of pre-pubertal and adult ages. Increases in the density and thickness of the collagen and elastic fibers were observed by histochemistry. TEM revealed wide distributions of collagen fibrils and large elastic fibers adjacent to the epithelial basal lamina and between the stromal cells, establishing contacts between them. These results indicate that the Guinea pig prostate simulates the stromal modifications observed in BPH in some aged animals after estrogen treatment at different ages, making it a good model for this disease. (c) 2005 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Experimental paracoccidioidomycosis in hamsters (Mesocricetus auratus): Gestational interactions

Paracoccidioides brasiliensis is a dimorphic fungus presenting specific steroid hormone receptors, both in the yeast and mycelial forms and estrogen inhibits the transition from mycelium to yeast. In the acute phase, the disease occurs with equal frequency in both sexes but in adults, females are spared. Placental fungal infection has been reported, but references to fetal infection have not been confirmed. We used 78 Syrian female hamsters divided into 3 groups: GI consisted of 30 infected mated females, GII of 20 infected unmated females and GIII of 28 uninfected mated females. Animals of group I were mated 4 weeks after infection and half of them were submitted to cesarean section on day 15 after successful mating; the other half was maintained and submitted to cesarean section and sacrificed 14 weeks after infection. Half of the animals of group II were sacrificed seven weeks and the other half 14 weeks after infection. Uninfected animals of group III were treated the same as the animals of group I. The animals were infected with strain 18 of P. brasiliensis by the intracardiac route. We evaluated the disease by the volume of granulomas in different organs, number of fungi in liver and spleen and the immunologic responses [ELISA, Double Immunodifusion (DID), Delayed Hypersensitivity Skin Test (DHT) and Macrophage Migration Inhibition (MMI)]. We studied the infection through the gestation by evaluation of the abortions, morphologic and clinic examinations of the fetuses. Our results showed that the infection did not transfer to the fetus through the placenta, but the number of abortions was larger among infected females. The newborns of GI females were smaller, weighed less and showed little vitality. The disease was more severe and disseminated in infected mated females, especially in the second sacrifice 14 weeks after inoculation, when the total volume of granulomas in them (56.3 mm) was much greater than in the infected unmated females (12 mm).

Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules

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

Concentração plasmática de diclofenaco sódico em cães, submetidos à fonoforese

The aim of this study was to evaluate the plasma concentration of diclofenac sodium (DS) in dogs submitted to diclofenaco phonophoresis and to evaluate if phonophoresis induces greater absorption of this drug in dogs. Five dogs were used in eight different groups at different times: One group received oral administration of 40mg of DS per dog and seven groups received topical application of emulgel DS. The topical application area was 20cm(2). A continuous ultrasound frequency of 1MHz and intensity of 0.4W cm(-2) was used. Blood collections were performed before the treatment (T0), and 1h (T1) and 4h (T2) after ultrasound application for all groups. DS concentrations in plasma were measured by high performance liquid choramatohraphy (HPLC). There was significant increase of DS plasma concentration only at T1 in the oral administration group. It was not possible to detect any concentration of DS in the plasma of dogs after topical application of DS, even after DS phonophoresis. The facilitation of transdermal penetration by ultrasound has not been verified under the protocol specified in this research.

Comparison of two methods of synchronization of estrus in brown brocket deer (Mazama gouazoubira)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Localization and hormonal regulation of endometrial matrix metalloproteinase-26 in the rhesus macaque

The current understanding of hormonal regulation of matrix metalloproteinase-26 (MMP-26) in the primate endometrium is incomplete. The goal of this work was to clarify estrogen and progesterone regulation of MMP-26 in the endometrium of ovariectomized, hormone-treated rhesus macaques.Ovariectomized rhesus macaques (n 66) were treated with estradiol (E-2), E-2 plus progesterone, E-2 followed by progesterone alone or no hormone. Endometrium was collected from the hormone-treated animals during the early, mid- and late proliferative and secretory phases of the artificial menstrual cycle. MMP-26 expression was quantified by real-time PCR, and MMP-26 transcript and protein were localized by in situ hybridization and immunohistochemistry and correlated with estrogen receptor 1 and progesterone receptor (PGR).MMP-26 was localized to glandular epithelium and was undetectable in the endometrial stroma and vasculature. MMP-26 transcript levels were minimal in the hormone-deprived macaques and treatment with E-2 alone did not affect MMP-26 levels. Treatment with progesterone both in the presence and absence of E-2 stimulated MMP-26 expression in the early and mid-secretory phases (P 0.001). MMP-26 expression preceded decidualization of endometrial stroma. MMP-26 levels then declined to baseline in the late secretory phase (P 0.01) despite continued E-2 plus progesterone treatment. Loss of detectable MMP-26 expression in the late secretory phase was correlated with late secretory phase loss of glandular epithelial PGR.Endometrial MMP-26 expression is dependent on the presence of progesterone in the early secretory phase and then gradually becomes refractory to progesterone stimulation in the late secretory phase. In the macaque, MMP-26 is a marker of the pre-decidual, secretory endometrium. During the second half of the late secretory phase, and during decidualization, MMP-26 loses its response to progesterone concurrent with the loss of epithelial PGR. The decline in MMP-26 levels between the mid- and late secretory phases may play a role in the receptive window for embryo implantation.

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

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

Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats

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

Considerações sobre o câncer localmente avançado de mama (CLAM) acrescidas de identificação dos receptores de estrogênios usando anticorpos monoclonais.

The effects of therapy in locally advanced breast cancer submitted to combined conventional telecobalt therapy plus chemotherapy with cyclophosphamide and 5-fluorouracil were studied in 49 patients. Associated to radical mastectomy in operable cases. Local tumor control was achieved in 86.7%. There were no local recurrences in those submitted to surgery but they reached 21.7% in inoperable patients who received only radiation therapy and chemotherapy. The median follow-up time for dead patients was 29.5 months and for living patients 79.3 months. The index of complete responses was 24.5% and the median disease free interval was 22.9 months. The overall survival rate, between three and five years, was 32.7%. Estrogen receptors were identified by using immunohistochemical assay ER-ICA and monoclonal antibody H222-SP gamma, Abbott. There were no differences in the complete response index, disease free interval and survival rates, among ER-positive and ER-negative patients, explained by the far advanced stage of the disease. ER-positivity was significantly correlated with histological features of the tumors: cell differentiation, presence of elastosis, absence of lymphocytic infiltration and absence of tumor necrosis.

Influence of cholecalciferol (Vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice

The course of systemic lupus erythematosus (SLE), an autoimmune disease, is markedly affected by hormones such as estrogen and prolactin. It is well known that heavy exposure to sunlight has deleterious effects on SLE, triggering episodes of the disease. Classical explanations for this occurrence suggest that UV radiation damages DNA, which becomes immunogenic, or induces exposure of the Ro antigen in keratinocytes. In recent years, it has been shown that vitamin D3 has important effects on the immune system. Thus, we proposed an alternative hypothesis, suggesting that UV radiation, by promoting vitamin D3 synthesis, could be a factor aggravating the course of SLE after exposure to sunlight. To test this hypothesis, we injected F1(NZBxW) mice, which are prone to developing SLE, with vitamin D3, and we demonstrated a worsening of the histopathological findings in the kidney. (C) 2000 Wiley-Liss, Inc.

Multimodal evoked potentials and the ovarian cycle in young ovulating women

There is controversy over how hormonal conditions influence cerebral physiology. We studied pattern-shift visual evoked potentials (PS-VEP), brain stem auditory evoked potentials (BAEP) and short-latency somatosensory evoked potentials (SSEV) in 20 female volunteers at different phases of the menstrual cycle (estrogen phase, ovulatory day and progesterone phase). Statistical analysis showed decreased latencies for P 100 (PS-VEP), N 19and P 22 (SSEV) waves in the progesterone phase compared with the estrogen phase. There was no significant difference between the estrogen and the ovulation day values. Comparing the three above stages, there were no significant differences in the brainstem auditory evoked potentials. The reduction of the latencies of the potentials generated in multisynaptic circuits provides the first consistent neurophysiological basis for a tentative comprehension of human pre-menstrual syndrome.