Proficiencies of Zingiber officinale against spine curve and vertebral damage induced by corticosteroid therapy associated with gonadal hormone deficiency in a rat model of osteoporosis.

This study was assessed to examine whether Zingiber officinale (ZO) can prevent spine disorder and trabecular microarchitecture disruption in osteoporotic murin model. Three groups of male rats were selected: Controls (CTRL), combined model of osteoporosis (CMO), in which rats were orchidectomized and treated with cortisol, and CMO treated with ZO (CMO + ZO). One month after the surgical procedures, the rats were sacrificed. Lumbar curve of the spine has been evaluated using the kyphotic method. The spines were submitted to histological and histomorphometric analysis and mineral (calcium and phosphorus) metabolism assessment. Compared to CTRL, the mean kyphotic angle (KA) was significantly higher in CMO rats. The spinal deconditioning associated decreased bone trabecular volume and a disrupted microarchitecture. A disorder was observed in the serum and bone levels of calcium and phosphorus in the combined severe osteopenia model. An increase in the level of TRAcP associated with an increase in osteoclast number and activity has been reported. These disturbances were reduced following the use of ZO in the CMO + ZO group. Finally, ginger might be an alternative therapeutic candidate for the treatment of severe osteopenia induced vertebral damage and spine curve disruption.

Corticosteroid treatment exacerbates bone osteopenia in mice with gonadal hormone deficiency-induced osteoporosis.

Gonadic deficiency and corticotherapy are important risk factors in the pathogenesis of osteoporosis. This study was outlined to assess the effects of combined orchidectomy (ORX) and corticosteroid (cortisol; CS) administration on bone remodeling and metabolism. Twenty-week-old male Swiss mice were randomized into four groups: either sham operated (sham), ORX, CS injected (CS), or ORX and CS injected (ORX+CS). After 28days, mice were euthanized. Both ORX and CS resulted in reduced trabecular volume, and mineral apposition rate and increased osteoclast number and activity. TRAcP levels were increased in ORX and CS mice, but reached highest values in ORX+CS. Bone and serum mineral content (calcium and phosphorus) were disrupted in ORX and CS groups when compared to Sham, and were more affected in ORX+CS group. Urinary calcium measures were increased in ORX, CS, and ORX+CS during the time course of the study. Increases were more prominent in ORX+CS. The differences between groups were generally more accentuated at ORX+CS group. Biochemical data showed a parallel extent to the histologic and histomorphometric changes. This study provides a valid pre-clinical model for severe and rapid osteopenia by ORX associated corticotherapy in which bone loss was significantly higher than either ORX or CS alones.

Chronic unpredictable stress and long-term ovariectomy affect arginine-vasopressin expression in the paraventricular nucleus of adult female mice.

Arginine-Vasopressin (AVP) may regulate the hypothalamic-pituitary-adrenal axis (HPA) and its effects on depressive responses. In a recent study, we demonstrated that Chronic Unpredictable Stress (CUS) depressive effects are enhanced by long-term ovariectomy (a model of post-menopause). In the present study, we investigated the effects of long-term ovariectomy and CUS on AVP expression in different subdivision of the paraventricular nucleus (PVN) of female mice. Both long-term ovariectomy and CUS affect AVP immunoreactivity in some of the PVN subnuclei of adult female mice. In particular, significant changes on AVP immunoreactivity were observed in magnocellular subdivisions, the paraventricular lateral magnocellular (PaLM) and the paraventricular medial magnocellular (PaMM), the 2 subnuclei projecting to the neurohypophysis for the hormonal regulation of body homeostasis. AVP immunoreactivity was decreased in the PaLM by both the long-term deprivation of ovarian hormones and the CUS. In contrast, AVP immunoreactivity was increased in the PaMM by CUS, whereas it was decreased by ovariectomy. Therefore, present results suggest morphological and functional differences among the PVN's subnuclei and complex interactions among CUS, gonadal hormones and AVP immunoreactivity.

Soy protein with or without isoflavones failed to preserve bone density in gonadal hormone-deficient male rat model of osteoporosis.

Soy with its isoflavones has been shown to positively influence bone mineral density in female ovariectomized rats; hence, we hypothesized a similar effect in orchidectomized (ORX) male rats. Forty male Sprague-Dawley rats, aged 95 days, were divided into 4 groups and were either sham operated (Sham) or ORX. The ORX groups were fed a soy protein-based diet (SOY), an isoflavone-depleted soy protein diet (SOY-), or a casein based diet for 65 days after surgery. Orchidectomy increased the rate of bone turnover, resulting in reduced bone mineral density and bone mineral content by 3.5% and 14%, respectively, and compromised biomechanical properties. The mean femoral length of ORX animals was also significantly shorter than Sham animals, but ORX rats that were fed SOY diet did not experience this reduction in bone length, implicating a role for soy protein in bone growth (4.02 ± 0.02, 3.93 ± 0.01, 3.99 ± 0.02, 3.91 ± 0.01 for Sham, ORX, SOY, SOY-, respectively). The SOY and SOY- positively influenced the biomechanical properties of bone such as yield and ultimate force, the measures of bone elasticity, and plasticity. In terms of bone histomorphometry, the data indicate that SOY- tends to reduce ORX-induced increase in bone turnover as evidenced by suppressed bone formation rate/mineralized surface by about 9%. Overall, our results indicated that soy protein, regardless of its isoflavone content, was unable to prevent the ORX-induced femoral decrease in bone density and mineral content. However, soy may enhance the quality of bone as indicated by increased yield force.

Aquaporin-4 deficiency exacerbates brain oxidative damage and memory deficits induced by long-term ovarian hormone deprivation and D-galactose injection.

Astrocyte dysfunction is implicated in pathogenesis of certain neurological disorders including Alzheimer's disease (AD). A growing body of evidence indicates that water channel aquaporin-4 (AQP4) is a potential molecular target for the regulation astrocyte function. Recently, we reported that AQP4 expression was increased in the hippocampus of an AD mouse model established by long-term ovarian hormone deprivation combined with D-galactose (D-gal) exposure. However, pathophysiological roles and mechanisms of AQP4 up-regulation remain unclear. To address this issue, age-matched female wild-type and AQP4 null mice underwent ovariectomy, followed by D-gal administration for 8 wk. AQP4 null mice showed more severe brain oxidative stress, spatial learning and memory deficits, and basal forebrain cholinergic impairment than the wild-type controls. Notably, AQP4 null hippocampus contained more prominent amyloid-ß production and loss of synapse-related proteins. These results suggested that ovariectomy and D-gal injection induced oxidative damage results in compensatory increases of AQP4 expression, and deficiency of AQP4 exacerbates brain oxidative stress and memory deficits. Therefore, regulation of astrocyte function by AQP4 may attenuate oxidative damage, offering a promising therapeutic strategy for AD.

Long-term deprivation of gonadal hormone accelerates brain aging in mice.

OBJECTIVE: The purpose of this study was to assess the effect of long-term deprivation of gonadal hormone on brain aging in mice to develop a model of gonadectomy-accelerated brain aging. METHODS: Male and female mice at 2 months old were orchiectomized (ORX) or ovarectomized (OVX) bilaterally or sham operated, and then they were fed for 10 months. The spatial learning and memory ability was tested using Morris Water Maze. The biomarkers of brain neuropathology were examined by Western blotting and immunohistochemistry. RESULTS: Ovarectomy mildly impaired spatial learning and memory of mice, while the impairment in ORX-mice was not significant. The amount of Nissl bodies decreased in the hippocampus and cortex of gonadectomied mice. The expression of beta-amyloid (Aß), beta-site APP cleaving enzyme 1 and phosphorylated-Tau increased in gonadectomied mice. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) decreased in the brain of OVX-mice, but neurotrophin-3 (NT-3) showed no change. We detected no decrease of NGF, BDNF or NT-3 in ORX-mice. TrkA expression decreased and p75(NTR) increased in the brain of gonadectomied mice. In all the above tests, there were no significant differences between young (2 months old) and sham operated (12 months old) mice. Alternations in the brain aging parameters were more obvious in OVX-mice than in ORX-mice. CONCLUSION: Long-term gonadal hormone deprivation by young-age gonadectomy accelerated mouse brain aging, which could serve as a valuable mouse model to study brain aging and aging-related pathological changes.

Hormonal deficiencies during and after Puumala hantavirus infection.

Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted in order to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in five patients and primary hypothyroidism in five patients. In addition, chronic subclinical testicular failure was found in five men. High creatinine levels and inflammatory markers during NE were associated with the acute central hormone deficiencies, but not with the chronic deficiencies. Hormonal defects are common during acute NE and, surprisingly, many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE.

Gonadal hormones modulate the potency of the disruptive effects of donepezil in male rats responding under a nonspatial operant learning and performance task.

In contrast to estrogen in female rats, testosterone in male rats may decrease cholinergic activity in the brain, thereby attenuating behaviors mediated by the cholinergic system. To investigate this possibility, the interactive effects of the gonadal hormones and donepezil, an acetylcholinesterase (AChE) inhibitor, on the responding of male rats were examined under a multiple schedule of repeated acquisition and performance of response sequences and on AChE activity in specific brain regions. Donepezil dose-effect curves (0.56-10 mg/kg) were determined in males that were gonadally intact, gonadectomized (GX), GX with testosterone replacement (GX+T) or GX with estradiol replacement (GX+E). In all four groups, donepezil produced dose-dependent rate-decreasing and error-increasing effects in the acquisition and performance components. However, disruptions of response rate and accuracy in both components occurred at lower doses in GX and GX+E males than in intact males. The GX+E males also had the highest percentage of errors under control (saline) conditions in the acquisition components. In terms of AChE activity, GX males had higher levels in the prefrontal cortex, striatum and hippocampus, but lower levels in the midbrain, compared with intact males; hypothalamic and cortical levels were comparable for the GX and intact groups. Together, these results in male rats indicate that the potency of donepezil's disruptive effects on the responding under a complex operant procedure requiring learning and performance of response sequences depends upon the gonadal hormone status, and that the effects of testosterone on cholinergic activity vary among brain regions.

Removal of ovarian hormones from mature mice detrimentally affects muscle contractile function and myosin structural distribution.

The purposes of this study were to determine the effects of ovarian hormone removal on force-generating capacities and contractile proteins in soleus and extensor digitorum longus (EDL) muscles of mature female mice. Six-month-old female C57BL/6 mice were randomly assigned to either an ovariectomized (OVX; n = 13) or a sham-operated (sham; n = 13) group. In vitro contractile function of soleus and EDL muscles were determined 60 days postsurgery. Total protein and contractile protein contents were quantified, and electron paramagnetic resonance (EPR) spectroscopy was used to determine myosin structural distribution during contraction. OVX mice weighed 15% more than sham mice 60 days postsurgery, and soleus and EDL muscle masses were 19 and 15% greater in OVX mice, respectively (P < or = 0.032). Soleus and EDL muscles from OVX mice generated less maximal isometric force than did those from sham mice [soleus: 0.27 (SD 0.04) vs. 0.22 N.cm.mg(-1) (SD 0.04); EDL: 0.33 (SD 0.04) vs. 0.27 N.cm.mg(-1) (SD 0.04); P < or = 0.006]. Total and contractile protein contents of soleus and EDL muscles were not different between OVX and sham mice (P > or = 0.242), indicating that the quantity of contractile machinery was not affected by removing ovarian hormones. EPR spectroscopy showed that the fraction of strong-binding myosin during contraction was 15% lower in EDL muscles from OVX mice compared with shams [0.277 (SD 0.039) vs. 0.325 (SD 0.020); P = 0.004]. These results indicate that the loss of ovarian hormones has detrimental effects on skeletal muscle force-generating capacities that can be explained by altered actin-myosin interactions.

Primary amenorrhea. Varied etiology.

Investigation of primary amenorrhea is usually initiated by the age of 14 years if there is delayed puberty absent secondary sexual characteristics and absent menses, or no menstruation within 4 years of the onset of adrenarche and thelarche. We established diagnosis in our 3 cases on the basis of chromosomal analysis, hormonal analysis, diagnostic laparoscopy, and histopathological examination of the samples biopsied. We identified 3 varied etiologies.

Síndrome del déficit androgenico del anciano o andropausia / No disponible

No disponible