Brain and testicular metabonomics revealed the protective effects of Guilingji on senile sexual dysfunction rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Guilingji (GLJ), which has been used to treat male diseases in China for centuries, contains 28 Chinese herbs and was previously established as an effective treatment for male sexual dysfunction. However, its mechanism of action remains unclear. AIM OF THE STUDY: To explore the efficacy and mechanism of action of GLJ in improving senile sexual dysfunction (SSD) in aging rats. MATERIALS AND METHODS: An aging rat model of SSD was induced by the subcutaneous injection of d-galactose (300 mg⋅kg-1) and used to analyse the effects of GLJ (different concentrations of 37.5, 75, and 150 mg⋅kg-1) on the mating of aging rats. At the end of the 8th week, histopathological analysis of testicular tissues, assessment of the hypothalamic-pituitary-gonadal (HPG) axis hormone levels in serum or brain, and metabonomics analysis of the brain and testicular tissue with liquid chromatography-mass spectrometry was performed to explore the mechanism of action of GLJ. RESULT: After treatment with GLJ, the mount and ejaculation latency levels were increased in the treatment group than those in model group (P < 0.05), moreover, the testicular morphology was improved. Gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels in rats were also improved significant (P < 0.05) compared with those in the model group. Furthermore, the metabonomics results in the testicular and brain tissue showed that GLJ improved SSD by adjusting amino acid and lipid metabolism. CONCLUSION: This study integrated the complementary metabolic profiles of the target tissues. GLJ might affect SSD rats by regulating amino acid and lipid metabolism and may modulate sensitivity to the signaling pathway in the HPG axis. This study provides an essential basis for the broad clinical application of GLJ.

The effect of hormonal levels and oxidative stress on bisphenol A and soy isoflavone reproductive toxicity in murine offspring.

Previous studies have suggested that human exposure to bisphenol A (BPA) and soy isoflavones (SIFs) can occur during pregnancy. The combination of these chemicals is hypothesized to have a toxic impact on the fetus. While BPA is an industrial chemical used widely in the manufacture of polycarbonate plastics and epoxy resins, SIFs are naturally occurring estrogen­like phytoestrogens. To determine the impact of the combination of BPA and SIFs on fetal development, the body weight, organ weight, anogenital distance and histopathological changes in the testes of F1 offspring were assessed in mice. Hormonal effects were determined by measuring serum levels of estrogen receptor (ESR), follicle­stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T). Additionally, mitochondrial DNA copy numbers, and the serum levels of malondialdehyde and superoxide dismutase, were determined to evaluate alterations in oxidative stress and potential toxicity. Exposure to BPA increased the body weight of the pups and reduced the ratio of anogenital distance to body weight, as well as testes weight. Moreover, BPA exposure also induced testicular lesions. The seminiferous tubules of testis were denatured in varying degrees and the lumen wall structure was disordered. The levels of ESR in all offspring and the T levels in male offspring significantly increased, compared with controls. Co­exposure to BPA and SIFs exacerbated these changes in body weight, testicular lesions and hormonal levels, relative to BPA exposure alone. Additionally, oxidative damage was only induced by high­dose BPA. Collectively, these findings suggested that BPA and SIFs could have synergistic effect on the reproductive system, which could be mediated by the regulation of ESR expression and testosterone release.

Green Coffea arabica Extract Ameliorates Testicular Injury in High-Fat Diet/Streptozotocin-Induced Diabetes in Rats.

Diabetes mellitus (DM) is a chronic endocrine disease characterized by persistent hyperglycemia. Oxidative damage, inflammatory cytokines, and apoptotic cell death play a major role in the induction and progression of male testicular damage. Plant-derived phytochemicals such as green coffee (Coffea arabica) can possess antidiabetic effects with little toxicity. The current study is aimed at investigating the therapeutic roles of green coffee in diabetic testicular injury stimulated by high-fat diet/streptozotocin administration. Diabetes mellitus was induced by a high-fat diet and a single dose of streptozotocin (STZ) (35 mg kg-1) in male albino rats. Diabetic animals were orally given two different concentrations of green coffee (50 mg kg-1 and 100 mg kg-1) for 28 days. The levels of testosterone, luteinizing hormone, and follicle-stimulating hormone and parameters of oxidative stress, inflammation, and apoptosis were measured. mRNAs and protein levels were detected quantitatively by real-time PCR and ELISA, respectively. In the diabetic group, the levels of testosterone, luteinizing hormone, and follicle-stimulating hormone showed a significant reduction while they increased significantly after green coffee treatment. A significant increase of antioxidant markers glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase along with decreased levels of lipid peroxides and nitric oxide was observed after green coffee treatment in the diabetic group. Finally, the levels of IL-1ß, TNF-α, Bax, and caspase-3 were also decreased in both treated groups (metformin and green coffee) when compared to the diabetic group. We conclude that testicular oxidative impairment induced by a high-fat diet (HFD) and STZ can be reversed by green coffee. Administration of green coffee could represent a promising therapeutic agent which can help the treatment of type 2 DM-induced testicular dysfunction.

Erythropoietin-producing hepatocellular receptor A7 restrains estrogen negative feedback of luteinizing hormone via ephrin A5 in the hypothalamus of female rats.

We have previously shown that systemic injection of erythropoietin-producing hepatocellular receptor A7 (EPHA7)-Fc raises serum luteinizing hormone (LH) levels before ovulation in female rats, indicating the induction of EPHA7 in ovulation. In this study, we aimed to identify the mechanism and hypothalamus-pituitary-ovary (HPO) axis level underlying the promotion of LH secretion by EPHA7. Using an ovariectomized (OVX) rat model, in conjunction with low-dose 17ß-estradiol (E2) treatment, we investigated the association between EPHA7-ephrin (EFN)A5 signaling and E2 negative feedback. Various rat models (OVX, E2-treated OVX, and abarelix treated) were injected with the recombinant EPHA7-Fc protein through the caudal vein to investigate the molecular mechanism underlying the promotion of LH secretion by EPHA7. Efna5 was observed strongly expressed in the arcuate nucleus of the female rat by using RNAscope in situ hybridization. Our results indicated that E2, combined with estrogen receptor (ER)α, but not ERß, inhibited Efna5 and gonadotropin-releasing hormone 1 (Gnrh1) expressions in the hypothalamus. In addition, the systemic administration of EPHA7-Fc restrained the inhibition of Efna5 and Gnrh1 by E2, resulting in increased Efna5 and Gnrh1 expressions in the hypothalamus as well as increased serum LH levels. Collectively, our findings demonstrated the involvement of EPHA7-EFNA5 signaling in the regulation of LH and the E2 negative feedback pathway in the hypothalamus, highlighting the functional role of EPHA7 in female reproduction.

Gonadoprotective ability of Vincetoxicum arnottianum extract against bisphenol A-induced testicular toxicity and hormonal imbalance in male Sprague Dawley rats.

Vincetoxicum arnottianum (Wight) of family Apocynaceae is a rich source of therapeutic alkaloids, phenolics and flavonoids. Study aims to evaluate the protective potential of methanol extract of Vincetoxicum arnottianum (VAM) on bisphenol A (BPA)-induced testicular toxicity in male Sprague Dawley rat. Quantitative analysis of VAM for total phenolic (TPC), total flavonoid (TFC) and total alkaloid content (TAC) along with HPLC analysis for polyphenolics was carried out. BPA-induced testicular toxicity was determined through analysis of antioxidant enzymes, DNA damages and testicular histopathology along with reproductive hormones in serum of rat. VAM was constituted of TFC (382.50 ± 1.67 µg GAE/mg), TPC (291.17 ± 0.82 µg RE/mg), TAC (16.5 ± 0.5%), ferulic acid (2.2433 µg/mg) and vanillic acid (2.1249 µg/mg). VAM co-administration to BPA-treated rats attenuated the toxic effects of BPA and restored the body and testis weights. Altered level of luteinizing hormone (LH), testosterone and follicle-stimulating hormone (FSH) in serum, and level of antioxidants (GSH, POD, CAT and SOD) and nitric oxide in testis tissues of BPA-induced toxicity were significantly restored by VAM. Histological and comet assay studies also sanctioned the protective potential of VAM in BPA-intoxicated rats. The presence of polyphenols and alkaloids might contribute towards the scavenging and ameliorative potential of VAM in testicular toxicity induced by BPA.

Amelioration effects of n-3, n-6 sources of fatty acids and rosemary leaves powder on the semen parameters, reproductive hormones, and fatty acid analysis of sperm in aged Ross broiler breeder roosters.

This study was conducted to evaluate the effects of dietary polyunsaturated fatty acids (PUFA) sources and rosemary leaves powder (RLP) on the semen quality, fatty acid analysis, and some reproductive hormones of senescent broiler breeder roosters. Thirty-five 45-wk-old Ross breeder roosters were randomly divided into 7 groups (5 birds/group), and received following treatments including control group (basal diet), fish oil (2%), corn oil (2%), an equal (50:50%) proportion of fish oil and corn oil (50:50%), fish oil (2%) with 5 g/kg capsulated RLP, corn oil (2%) with 5 g/kg capsulated RLP, and an equal (50:50) proportion of fish oil and corn oil (50:50%) with 5 g/kg capsulated RLP of diet for 60 D, during which time their seminal characteristics were evaluated every 20 D. At the end of the trial (on day 60), semen samples were tested for determination of sperm fatty acid analysis, lipid peroxidation, and some reproductive hormones. Results showed that feeding fish oil and fish/corn oil with RLP was associated with an increase in docosahexaenoic acid (C22:6n-3) and docosatetraenoic acid (C22:4n-6) in sperm. The fish oil diet increased the proportion of n-3 fatty acids in sperm, and as a consequence, the (n-6)/(n-3) ratio also decreased (P < 0.05). RLP (5 g/kg) to the fish and fish/corn-oil (50:50%)-based diet resulted in improvement in sperm concentration, total motility (%), sperm progressive motility (%), membrane integrity, and viability in terms 0 to 60 day trial (P < 0.05). Diets and age interacted to positively affect sperm concentration and sperm membrane integrity. Also this herbal antioxidant decreased the seminal content of malondialdehyde (MDA) significantly (P < 0.05). Testosterone and LH serum levels of reproductive hormones were significantly higher in fish and fish/corn-oil with RPL (50:50%)-based diet than other groups (P < 0.05). It can be concluded that RLP as an antioxidant could remarkably improve the effects of n-3 and n-3/n-6 PUFA on sperm characteristics, seminal MDA, and hormones levels in aged breeder roosters. The susceptibility of semen to lipid peroxidation was increased in chickens fed without RLP. Future studies are needed to disclose the causal mechanisms involved.

Sex Differences in Steroid Receptor Coexpression and Circadian-Timed Activation of Kisspeptin and RFRP-3 Neurons May Contribute to the Sexually Dimorphic Basis of the LH Surge.

In rodents, the ovulation-inducing luteinizing hormone (LH) surge is sexually dimorphic, occurring only in females, but the reasons for this sex difference are unclear. Two neuropeptides, kisspeptin and RFamide-related peptide 3 (RFRP-3), are hypothesized to regulate the gonadotropin-releasing hormone (GnRH)/LH surge. In females, both of these systems show circadian changes coincident with the LH surge, but whether males show similar temporal changes under comparable hormonal conditions is unknown. Here, we evaluated circadian time (CT)-dependent changes in gene expression and neuronal activation of Kiss1 and Rfrp neurons of female and male mice given identical LH surge-inducing estrogen regimens. As expected, females, but not males, displayed a late afternoon LH surge and GnRH neuronal activation. Kiss1 expression in the anteroventral periventricular nucleus (AVPV) was temporally increased in females in the late afternoon, whereas males demonstrated no temporal changes in AVPV Kiss1 expression. Likewise, neuronal activation of AVPV Kiss1 neurons was dramatically elevated in the late afternoon in females but was low at all circadian times in males. Estrogen receptor α levels in AVPV Kiss1 neurons were sexually dimorphic, being higher in females than males. AVPV progesterone receptor levels were also higher in females than males. Hypothalamic Rfrp messenger RNA levels showed no CT-dependent changes in either sex. However, Rfrp neuronal activation was temporally diminished in the afternoon/evening in females but not males. Collectively, the identified sex differences in absolute and CT-dependent AVPV Kiss1 levels, AVPV sex steroid receptor levels, and circadian-timed changes in neuronal activation of both Kiss1 and Rfrp neurons suggest that multiple sexually dimorphic processes in the brain may underlie proper LH surge generation.

Effects of chronic DHEA treatment on central and peripheral reproductive parameters, the onset of vaginal opening and the estrous cycle in female rats.

The neonatal and/or prepubertal androgen milieu affects sexual maturation and reproductive function in adulthood. However, the effects of chronic dehydroepiandrosterone (DHEA) treatment on reproductive functions have not been fully elucidated. Therefore, the reproductive phenotypes and parameters of rats that had been subjected to chronic DHEA treatment were evaluated in this study. The chronic DHEA-treated (from postnatal day 23-12 weeks of age) rats exhibited earlier vaginal opening, indicating that DHEA treatment promotes sexual maturation. In addition, the estrus phase lasted longer in the DHEA-treated rats, suggesting that their estrous cycles had been disrupted. As the DHEA-treated rats' serum luteinizing hormone levels and hypothalamic Kiss1 mRNA expression levels were decreased and their uterine weight was increased, DHEA and/or estrogen might directly affect reproductive phenotypes. While DHEA treatment caused changes in body weight and body composition in chronic testosterone-treated models in previous studies, no such changes were seen in the present study.

Protective effects of Artocarpus altilis (Moraceae) on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats.

Cadmium (Cd) is a major environmental toxicant and an endocrine disruptor. We investigated the protective effects of methanol extract of Artocarpus altilis (AA) against Cd-induced testicular damage in rats while quercetin (Que) served as standard. The total flavonoids and phenolic contents (TFC and TPC), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (OH) radicals scavenging activities of AA were determined. In vivo, thirty male Wistar rats were assigned to six groups and orally treated with corn oil (control), Cd alone, Cd+Que, Cd+AA, Que and AA alone. Que and AA were given at doses of 25 and 200 mg kg(-1), respectively, for 3 weeks and challenged with two doses of Cd (1.5 mg kg(-1)). Results showed that TFC and TPC of AA increased with increase in concentration. AA scavenged DPPH and OH radicals in a dose-dependent manner. Administration of Cd significantly increased the relative weight of testis of rats. Lipid peroxidation was significantly increased while antioxidant parameters decreased in testis of Cd-treated rats. Also, Cd-treated rats had significantly reduced sperm count, motility, sialic acid, luteinising hormone and testosterone relative to controls. Pre-treatment with AA or Que significantly attenuated the biochemical alterations observed in Cd-treated rats. Overall, AA protects against Cd-induced testicular damage via antioxidative mechanism.

The effect of coenzyme Q10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study.

OBJECTIVE: It has been shown that coenzyme Q(10) (CoQ(10)) supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters. In present study, we evaluated the effects of coenzyme CoQ(10) supplementation on semen parameters and pregnancy rates in infertile men with idiopathic OAT. PATIENTS AND METHODS: Two hundred and eighty-seven infertile men with idiopathic OAT were recruited in this study. These patients were treated with CoQ(10) 300 mg orally twice daily for 12 months. Two semen analyses and determination of resting levels of sex hormones were done in all participants. Patients were followed up for another 12 months after CoQ(10) discontinuation. RESULTS: Mean sperm concentration, sperm progressive motility, and sperm with normal morphology improved significantly after 12-month CoQ(10) therapy by 113.7, 104.8, and 78.9%, respectively (all Ps < 0.05). The overall pregnancy rate was 34.1% within a mean of 8.4 ± 4.7 months. CONCLUSIONS: CoQ(10) supplementation improves semen quality with beneficial effect on pregnancy rate.

Hormonal and Histomorphologic Effects of Azadirachta indica leaf Extract on the Pars Anterior of Wistar Rats / Efectos Hormonales e Histomorfológicosdel Extracto de la Hoja de Azadirachta indica en la Pars Anterior de Ratas Wistar

Azadirachta indica is a tree whose medicinal value is unquantifiable. Any part of the tree can be used in the treatment of malarial infection. Reports have indicated its antifertility effects, and this necessitated this study on the effects of the methanol leaf extract on serum luteinizing (LH) and follicle stimulating hormones (FSH) levels and the histomorphology of the pars anterior of Wistar rats. Thirty adult male Wistar rats were equally divided into 3 groups of A, B and C. Group A was the control and the animals received distilled water orally, while groups B and C were treated with 200mg/kg and 400mg/kg respectively of the leaf extract by oral gavage for fourteen days. On day fifteen, the animals were sacrificed by chloroform anaesthesia. Blood was obtained from their hearts, while the skull was opened to assess the hypophysis. Hormonal assay showed that luteinizing (LH) and follicle stimulating (FSH) hormone levels in the serum were lower in groups B and C treated with 200mg/kg and 400mg/kg respectively of the leaf extract, while that of LH were significant (P<0.001). Histomorphologic sections of the pars anterior revealed reduced acidophil and basophil populations, with prominent degranulated chromophobes which were larger in the group treated with 400mg/kg of A. indica leaf extract. This group also presented hypertrophy of the basophils compared to the control. In conclusion, methanol leaf extract of A. indica decreases serum LH and FSH and caused histomorphologic changes in the pars anterior of adult male Wistar rats.

Azadirachta indica es un árbol cuyo valor medicinal es invaluable. Cualquier parte del árbol se puede utilizar en el tratamiento de la infección por malaria. Reportes han indicado su efecto antifertilidad, lo que requirió estudiar los efectos del extracto metanólico de la hoja sobre los niveles séricos de las hormonas luteinizante (LH) y folículo estimulante (FSH) y la histomorfología de la pars anterior de ratas Wistar. Treinta ratas Wistar adultas fueron divididas en tres grupos. El grupo A fue utilizado como control y los animales recibieron agua destilada por vía oral, mientras que los grupos B y C fueron tratados con 200 mg/kg y 400 mg/kg respectivamente, con extracto de hoja mediante una sonda nasogástrica durante catorce días. A los quince días, los animales fueron sacrificados por anestesia con cloroformo. Se obtuvo sangre desde sus corazones, mientras que el cráneo fue abierto para evaluar la hipófisis. Los ensayos hormonales mostraron que los niveles en suero de la LH y FSH se redujeron en los grupos B y C, tratados con 200 mg/kg y 400 mg/kg respectivamente, siendo la reducción de LH significativa (p<0,001). Secciones histomorfológicos de la pars anterior revelaron una reducción de las poblaciones acidófilas y basófilas, con prominentes cromófobos degranulados que fueron mayores en el grupo tratado con 400 mg/kg del extracto de A. indica. Este grupo también presentó hipertrofia de los basófilos en comparación con el control. En conclusión, el extracto alcohólico de la hoja de de A. indica disminuye el nivel sérico de LH y FSH y provoca cambios histomorfológicos en la pars anterior de ratas Wistar adultas.

Effect of methotrexate and leucovorin on female reproductive tract of albino rats.

Methotrexate (MTX) an antifolate drug and leucovorin its antidote, are used in the treatment of both neoplastic and non-neoplastic diseases in young women. We hypothesize that MTX treatment might comprise a deleterious effect on fast proliferating reproductive cells, an unavoidable and unwanted side effect. MTX given dose dependently to rats for 20 days prevented vaginal cyclicity and caused a reduction in serum progesterone and estradiol. External morphology of reproductive tract displayed thinning of organs and reduction in their weights. To reveal mechanism of MTX action, we examined the histology of ovary, oviduct, uterus, cervix and vagina. Results suggested that in a dose-dependent fashion MTX restrained preantral and antral follicular growth in ovary. Epithelium and stroma of oviduct, uterus, cervix and vagina were disrupted and lost their normal structures. Such alterations in ovarian function raised serum follicle stimulating hormone, luteinizing hormonal profiles. Expression of steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage gene, which are both essential for steroidogenesis, markedly decreased in ovary upon MTX treatment. Total RNA, DNA and protein concentrations, glucose 6 phosphate dehydrogenase, lactate dehydrogenase and alkaline phosphatase enzyme activities in ovary were distinctly altered. Leucovorin supplementation and withdrawal of the treatment, improved MTX caused effects partially. These results for the first time indicate that the malfunction of female reproductive organs by MTX treatment in young women is not only correlated to the disrupted circulating levels of hormones and histoarchitecture of tissues but also discrepancies in steroidogenic genes and hormone regulated enzyme activities in ovary.

Modulatory effects of lipoic acid and selenium against cadmium-induced biochemical alterations in testicular steroidogenesis.

Exposure to toxic metals including cadmium has become an increasingly recognized source of illness worldwide. Cadmium (Cd(2+) ) is one of the environmental pollutants affecting various tissues and organs including testis. The protective effect of lipoic acid and selenium on Cd(2+) -induced testicular damage was investigated. Accordingly, male Wistar rats were allocated into four groups (n = 8; each). Gp I: (control), whereas the other 3 groups received CdCl(2) (2 mg/kg, i.p. for 28 days) alone or in combination with either (i) lipoic acid (35 mg/kg, p.o) or (ii) selenium (0.35 mg/kg, p.o) throughout the experiment. Serum testosterone, luteinizing hormone and follicle-stimulating hormone levels significantly decreased in the Cd(2+) -exposed rats. The activities of testicular key androgenic enzymes, 3ß-hydroxysteroid dehydrogenase and 17 ß-HSD significantly decreased in Cd(2) exposed rats compared to the control counterparts. In addition, the activities of testicular marker enzymes were significantly altered in cadmium-treated animals. Significant reductions in body and testicular weight as well as antioxidant status were also observed in Cd(2+) -exposed rats. Moreover, some testicular metal levels were altered. Lipoic acid and selenium significantly increased serum testosterone level and restored testicular activity of 3ß-HSD and 17 ß-HSD and were effective in modulation of most of the measured biochemical parameters. The biochemical parameters were further confirmed with histopathological findings. In conclusion, the present study demonstrated the beneficial influences of lipoic acid and selenium in reducing harmful effects of Cd(2+) in rats' testes.

Luteinizing hormone reduction by the male potency herb, Butea superba Roxb.

To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group): distilled water, Butea superba (BS)-10, BS-50, BS-250, and testosterone propionate (TP). They received 0, 10, 50, and 250 mg·kg body weight-1·day-1 BS in distilled water by gavage and 6 mg·kg body weight-1·day-1 TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.

Luteinizing hormone reduction by the male potency herb, Butea superba Roxb.

To determine if Butea superba Roxb., a traditional Thai male potency herb, has androgenic activity in 60-day-old male Wistar rats, we measured its effects on the pituitary-testicular axis and sex organs. Intact and orchidectomized adult male rats were subdivided into five groups (10 rats/group): distilled water, Butea superba (BS)-10, BS-50, BS-250, and testosterone propionate (TP). They received 0, 10, 50, and 250 mg·kg body weight(-1)·day(-1) BS in distilled water by gavage and 6 mg·kg body weight(-1)·day(-1) TP sc, respectively, during the 30-day treatment period. Blood was collected every 15 days and luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. Changes of weight and histological appearance of sex organs were determined at the end of the 30-day treatment and 15-day post-treatment periods. TP treatment reduced serum FSH and LH levels and significantly increased the weight of the seminal vesicles and epididymis, in accordance with histopathological changes, in both intact and orchidectomized rats. No changes in serum testosterone, LH, and FSH levels were observed in any of the intact rats treated with BS, but a significant increase in seminal vesicle weight was observed only in the BS-250 group. Although a significant reduction in serum LH was detected in the BS-50 and BS-250 groups of orchidectomized rats, no significant change in weight or histology of sex organs was observed. Thus, we conclude that B. superba needs endogenous testosterone to work synergistically to stimulate the accessory sex organ of intact animals and can potentially exhibit an LH reduction effect in orchidectomized animals.

A novel animal model to study hot flashes: no effect of gonadotropin-releasing hormone.

OBJECTIVE: Menopausal hot flashes compromise the quality of life for most women. The physiological mechanisms underlying hot flashes remain poorly understood, and the absence of an animal model to investigate hot flashes hinders investigations in this field. METHODS: We first developed the sheep as a model to study peripheral skin temperature changes using fever-inducing lipopolysaccharide (LPS; 200 microg/kg) administered to ovary-intact ewes. Because a strong correlation between luteinizing hormone pulses and hot flashes has previously been reported, we then determined whether intravenous gonadotropin-releasing hormone (GnRH; 1 mg), a dose sufficient to elevate cerebrospinal fluid-GnRH concentrations, could modulate ear skin temperature in both ovariectomized and low-estrogen-replaced ovariectomized ewes. RESULTS: Some ewes responded to LPS in heart rate and abdominal temperature, but there was no significant effect on either parameter or cheek temperature for the group. In contrast, LPS injection caused a significant (P < 0.001) change in skin temperature at the ear. Ear temperature showed no significant change in response to GnRH relative to control injections in both ovariectomized and low estrogen ewes. CONCLUSIONS: We developed a model animal system in the ewe that can accurately detect small changes in peripheral skin temperature. This system has the potential to be extremely useful in future studies investigating the pathology of hot flashes and holds several advantages over previous model systems developed for this research. GnRH per se does not seem to be involved in thermoregulatory events.

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Insulin modulation of luteinizing hormone secretion in normal female volunteers and lean polycystic ovary syndrome patients.

BACKGROUND/AIMS: Endocrine features of polycystic ovary syndrome (PCOS) include altered ovarian steroidogenesis, hyperinsulinemia and abnormal luteinizing hormone (LH) secretion. This study was undertaken to further evaluate the role of insulin to modulate LH secretion in lean PCOS patients with normal insulin sensitivity and normal volunteers. METHODS: The study was performed in five nonobese patients diagnosed with PCOS on the basis of amenorrhea and a polycystic morphology at ovarian ultrasound, and 5 normal controls in early to mid-follicular phase and matched for weight and age. All subjects were phenotyped, and then admitted for 12 h of frequent (q 10') blood sampling on two separate occasions, once for a baseline study and the other time for a hyperinsulinemic and euglycemic clamp study. LH was measured in samples obtained throughout each admission in order to perform LH pulse analysis. RESULTS: Baseline LH secretion in PCOS subjects was significantly different from controls: they had higher LH levels, higher LH/FSH ratios as well as a faster LH pulse frequency than normal women. Insulin administration did not affect the pattern of LH secretion of PCOS patients, whereas it significantly increased the LH pulse frequency while decreasing the LH interpulse intervals in the controls. CONCLUSIONS: These data confirm that an abnormal pattern of LH secretion characteristic of PCOS can be observed in lean patients, and appears independent of peripheral insulin levels. Furthermore, our results in lean controls provide the first direct evidence that peripheral insulin can modulate the activity of hypothalamic gonadotropin-releasing hormone (GnRH) neurons in the human.

The effects of GABA agonists on glutamic acid decarboxylase, GABA-transaminase, activin, salmon gonadotrophin-releasing hormone and tyrosine hydroxylase mRNA in the goldfish (Carassius auratus) neuroendocrine brain.

GABA plays a pivotal role in reproduction by regulating luteinising hormone (LH) release from the anterior pituitary. Current evidence indicates that there is a prominent stimulatory effect of GABA on LH release in teleost fish which results from enhanced gonadotrophin-releasing hormone (GnRH) release and decreased dopamine turnover in the brain and pituitary. We hypothesised that there may be additional mechanisms underlying LH release in goldfish and investigated the relative mRNA levels of GABA synthesising enzymes (GAD65 and GAD67), degrading enzyme (GABA-T), activin betaa and betab, salmon GnRH (sGnRH), and tyrosine hydroxylase (TH) with the real-time reverse transcriptase-polymerase chain reaction after GABA agonist treatment. Sexually regressed female goldfish were i.p. injected with either the GABA(A) agonist muscimol (1 microg/g body weight) or the GABA(B) agonist baclofen (10 microg/g body weight). Both agonists significantly increased serum LH after 6 h. Muscimol decreased GAD65 (approximately ten-fold), GABA-T (approximately 15-fold) and TH (approximately three-fold) mRNA in the telencephalon. Baclofen significantly reduced GAD67 (approximately two-fold) and GABA-T (approximately two-fold) mRNA levels in the hypothalamus. Activin betaa, but not activin betab, steady-state mRNA was increased approximately three- to four-fold in both the hypothalamus and telencephalon after baclofen treatment. There was no change in sGnRH mRNA levels in either tissue after GABA agonist treatment. We show that the GABA(A) and GABA(B) receptor agonists have differing and rapid effects on gene transcription in the goldfish neuroendocrine brain and, by affecting specific targets, we identify putative genomic mechanisms underlying GABA-stimulated LH release in fish.

Antifertility activity of the methanolic leaf extract of Cissampelos pareira in female albino mice.

meenakshi Cissampelos pareira Linn. is one of the folk medicinal plants commonly used as antifertility agent in some places of India. The aim of the present study was to evaluate the validity of the antifertility effect of the leaf extract. Cissampelos pareira leaf extract, when administered orally, altered the estrous cycle pattern in female mice, prolonged the length of estrous cycle with significant increase in the duration of diestrus stage and reduced significantly the number of litters in albino mice. The analysis of the principal hormones involved in estrous cycle regulation showed that the plant extract altered gonadotropin release (LH, FSH and prolactin) and estradiol secretion. The results indicated the antifertility effect of Cissampelos pareira leaf extract in female albino mice. The oral LD50 of the extract was found to be 7.3 g/kg in mice.