Higher Luteinizing Hormone Levels Research Articles

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men

The association between the Y chromosome haplogroup D2 and risk of azoospermia and low sperm motility has been previously studied, and it was indicated that haplogroups DE (YAP lineage) are associated with prostate cancer risk in Japanese males. Our assumption had been that Y chromosome haplogroups may be associated with sex hormone levels, because sex hormones have been deemed responsible for spermatogenesis and carcinogenesis. In this study, we assessed the association between Y chromosome haplogroups and sex hormone levels, including those of testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin-B, and calculated free testosterone (cFT), in 901 young men from the general Japanese population (cohort 1) and 786 Japanese men of proven fertility (cohort 2). We found that the haplogroup D2a1 was significantly associated with high LH levels in a combined analysis involving two cohorts (β = 0.068, SE = 0.025, p = 0.0075), following correction for multiple testing. To date, this result is the first evidence that implicates Y chromosome haplogroups in an association with sex hormone levels.

Insulin receptor signaling in the GnRH neuron plays a role in the abnormal GnRH pulsatility of obese female mice.

Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These results suggest that in the obese state, insulin receptor signaling in GnRH neurons increases GnRH pulsatile secretion and consequent LH secretion, contributing to reproductive dysfunction.

Symptom patterns and phenotypic subgrouping of women with polycystic ovary syndrome: association between endocrine characteristics and metabolic aberrations

What are the potential endocrine characteristics related to risk and severity of metabolic disturbances in women with polycystic ovary syndrome (PCOS)? Women with PCOS could be subtyped into four subgroups according to heterogeneous endocrine characteristics and the major predictive endocrine factors for metabolic aberrations among different subgroups were free androgen index (FAI) and luteinizing hormone (LH) levels. Women diagnosed with PCOS present with highly heterogeneous phenotypes, including endocrine and metabolic aberrations. Different strategies have been proposed to predict the metabolic outcomes but whether the endocrine factors can solely predict the metabolic aberrations is still inconclusive. A cross-sectional study including 460 patients recruited from a reproductive endocrinology outpatient clinic of a tertiary medical center. Patients with PCOS diagnosed according to the 2003 Rotterdam criteria were studied. Clinical history recorded by questionnaires, anthropometric measurements, biochemistry tests after an overnight fast, and pelvic ultrasonography were collected from all patients. Applying a matrix visualization and clustering approach (generalized association plots), the patients were divided into four distinct clusters according to the correlation with four endocrine parameters. Each cluster exhibited specific endocrine characteristics and the prevalence of metabolic syndrome (MS) was significantly different among the clusters (P < 0.0001). The high-risk subgroups for MS included one cluster with higher mean (SD) FAI (39.6 (14.7) in cluster 4), and another one with lower mean (SD) FAI (10 (6.4) in cluster 2). A common endocrine characteristic of these two metabolically unhealthy clusters was relatively lower LH level. Contrarily, higher LH level (≧15 mIU/ml) during early follicular phase was found to be the best indicator of the metabolically healthy cluster (cluster 1). While high FAI level did correlate with more severe metabolic aberrations, high LH level showed better predictive value than low FAI level to become a metabolically healthy cluster. The results should be applied to other populations with caution due to racial or environmental differences. Another limitation is a lack of normal non-PCOS control in our study. Stratifying women with PCOS into meaningful subtypes could provide a better understanding of related risk factors and potentially enable the design and delivery of more effective screening and treatment intervention. This study was supported by grant NSC 100-2314-B002-027-MY3 from the National Science Council of Taiwan. Nil.

Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support-Results of a Prospective, Randomized, Comparative Study.

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols.

Late-onset hypogonadism: beyond testosterone.

Late-onset hypogonadism is defined as a combination of low testosterone (T) levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell (dys)function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone (LH) and 25-hydroxyvitamin D levels. These markers help in identifying the so-called “subclinical” hypogonadism (normal T, high LH levels). Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option (cholecalciferol – the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D) in these patients. We studied 66 patients with classic hypogonadism (total T [TT] <12 nmol l−1, LH ≥ 8 IU l−1) (n = 26) and subclinical hypogonadism (TT ≥ 12 nmol l−1, LH ≥ 8 IU l−1) (n = 40) and low 25-hydroxyvitamin D (<50 nmol l−1). Subjects received cholecalciferol (5000 IU per week) (n = 20) or calcidiol (4000 IU per week) (n = 46), and 25-hydroxyvitamin D and parathyroid hormone (PTH) were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PTH levels in both groups of men with hypogonadism (primary, n = 16 and subclinical, n = 30), whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D (calcidiol), and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.

Melatonin promotes superovulation in sika deer (Cervus nippon).

In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.

Androgen Deficiency as a Biological Determinant of Frailty: Hope or Hype?

The role of androgen deficiency as a biological determinant of frailty has received considerable attention. Cross-sectional studies have shown that low bioavailable testosterone (BT) is associated with prevalent frailty. High levels of luteinizing hormone and sex hormone binding globulin are also associated with prevalent frailty. Longitudinal studies have had mixed results, suggesting, for the most part, that a decline in BT over time is associated with progression of frailty. A number of potential biases were found in the current body of evidence, including misclassification bias (due to testosterone assays that were insensitive in lower ranges), selection bias (due to preferential inclusion of healthier individuals), and residual confounding (due to correlation of low testosterone with several disease states and adverse health characteristics). Consideration of these biases is vital to ensure that future epidemiological studies and interventional trials generate valid conclusions.

Anti-Müllerian hormone, testosterone and free androgen index following the dose-adjusted unilateral diathermy in women with polycystic ovary syndrome

ObjectiveThe aim of this study was to investigate changes of anti-Müllerian hormone, testosterone and free androgen index after two diathermy methods. We have also aimed at evaluating prognostic value of these parameters for an ovulatory response. Study designThis prospective, comparative study included ninety-six women with polycystic ovary syndrome unresponsive to clomiphene citrate. Patients were assigned to two groups; the first group underwent unilateral laparoscopic ovarian drilling with thermal doses adjusted to ovarian volume: median of 720J (IQR), while the second group underwent bilateral drilling with fixed doses of 1200J. Anti-Müllerian hormone (AMH), testosterone (T), free androgen index (FAI)and luteinizing hormone (LH) were measured at baseline, at 1st and 6th month of follow up. ResultsAMH, T and LH levels significantly decreased (P<0.001, P≤0.024, P<0.001) after diathermy in both responders and nonresponders from either treatment group. On contrary, FAI levels (P<0.001) significantly changed only in responders, irrespective of the treatment. In 1st and 6th month of follow up median levels of AMH, T and FAI among responders from different treatment groups were equivalent, whereas the responders in bilateral group had higher LH levels in the 1st month of follow up (P=0.003). Nonresponders differed between treatment groups only in AMH level which was decreased in unilateral group throughout the follow up (P≤0.021). The baseline value of T (semi-standardized coefficient, β=−0.28) and value of T in the 1st month (β=−0.72) after the diathermy were significant and consistent indicator of the response to therapy within 6months and the ovulation response in the 1st month. ConclusionsThe value of T is the strongest and consistent indicator of ovulatory response after diathermy.Clinical Trial Registration: www.ClinicalTrials.gov , NCT01833949.

Adrenocortical production is associated with higher levels of luteinizing hormone in nonobese women with polycystic ovary syndrome.

Objective. Insulin resistance (IR) and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS). The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese) and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX) 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH) levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r = −0.52; P = 0.001) and insulin (r = −0.47; P = 0.003) and positive correlation with LH (r = 0.40; P = 0.016). Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

Effects of Prenatal Stress on the Activity of the Pituitary-Ovarian System in Female Rats

The comparative analysis of hormonal status was performed in mature female rats with experimental deficiency of estrogens, which mothers were exposed to stress during pregnancy. High levels of follicle-stimulating hormone and luteinizing hormone, and significantly lower amount of estradiol were observed in intact prenatally stressed females in comparison with intact non-stressed female rats. The increase in the levels of follicle-stimulating hormone and luteinizing hormone, and the decrease in estradiol concentration were more pronounced in blood serum of prenatally stressed ovariectomized rats as distinct from intact non-stressed and prenatally stressed female rats, and non-stressed ovariectomized female rats. We can conclude that prenatally stressed ovariectomized rats were characterized by an increased sensitivity to exogenous hormonal interventions and high lability of functional state of the pituitary-ovarian system.

Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis.

Abstract Combinations of fructose- and fat-rich diets in experimental animals can model the human metabolic syndrome (MS). In rats, the increase in blood pressure (BP) after diet manipulation is sex related and highly dependent on testosterone secretion. However, the extent of the impact of diet on rodent hypophysial-testicular axis remains undefined. In the present study, rats drinking a 10% fructose solution or fed a high-fat (35%) diet for 10 weeks had higher plasma levels of luteinizing hormone (LH) and lower plasma levels of testosterone, without significant changes in circulating follicle-stimulating hormone or the weight of most reproductive organs. Diet manipulation brought about a significant increase in body weight, systolic BP, area under the curve (AUC) of glycemia after an intraperitoneal glucose tolerance test (IPGTT), and plasma low-density lipoprotein cholesterol, cholesterol, triglycerides, and uric acid levels. The concomitant administration of melatonin (25 μg/mL of drinking water) normalized the abnormally high LH levels but did not affect the inhibited testosterone secretion found in fructose- or high-fat-fed rats. Rather, melatonin per se inhibited testosterone secretion. Melatonin significantly blunted the body weight and systolic BP increase, the increase in the AUC of glycemia after an IPGTT, and the changes in circulating lipid profile and uric acid found in both MS models. The results are compatible with a primary inhibition of testicular function in diet-induced MS in rats and with the partial effectiveness of melatonin to counteract the metabolic but not the testicular sequelae of rodent MS.

Two Hormones May Predict Recividism of Sex Offenders

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessTwo Hormones May Predict Recividism of Sex OffendersJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:1 Mar 2013https://doi.org/10.1176/appi.pn.2013.3a4AbstractWhile testosterone plays a role in sexual function and in sexual and nonsexual aggression, the sex hormones LH and FSH appear to better predict recidivism.One of Canada’s leading sexual-offender experts, psychiatrist John Bradford, M.D., and his team conducted a 20-year study of almost 800 male sexual offenders and discovered that the gonadotrophic sex hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were better predictors of recidivism than the sex hormone testosterone was.“This study is an important one, with a surprising finding that gonadotrophic hormones were better predictors of recidivism for sexual crimes than testosterone,” Richard Krueger, M.D., told Psychiatric News. Krueger, an associate clinical professor of psychiatry at Columbia University College of Physicians and Surgeons, has conducted extensive research on sexual offenders. “Given the prominent role of testosterone in sexual function and in sexual and nonsexual aggression, studies that prospectively examine biological in addition to behavioral variables in humans are extremely important.”Bradford, who is clinical director of the Forensic Treatment Unit of the Royal Ottawa Health Group in Ottawa, Canada, and colleagues included 771 adult male sex offenders in their study. About two-thirds were pedophiles, over 20 percent were exhibitionists, 10 percent were rapists of adult women, and the remainder had engaged in other forms of sexual offenses. The men had been evaluated between 1982 and 1996 at a university-affiliated forensic sexual behaviors clinic for levels of LH and FSH, total testosterone (testosterone bound to proteins in the blood), and free testosterone (testosterone not bound to proteins in the blood). Although only 2 percent of testosterone is free, it is believed that it is more active than total testosterone is.Recidivism data for the subjects were obtained in 2002 from a national database maintained by the Royal Canadian Mounted Police. This means that some subjects had been observed for up to 20 years in the community; the average observation time was 11 years. The percentage of subjects who reoffended sexually during the follow-up period was 18 percent, the researchers found. Finally they assessed whether there were any links between subjects’ initial LH, FSH, or testosterone levels and their later recidivism.LH and FSH levels were significantly associated with recidivism outcomes, whereas levels of total testosterone and free testosterone were not, Bradford and his team reported in the December 2012 Journal of the American Academy of Psychiatry and the Law.As for their study’s implications, “Our results do not support the idea that abnormal hormone levels explain sexual offending,” the researchers said. “Instead, relatively high levels of LH and FSH must interact with other actors to increase the likelihood of sexual aggression.”But what other factors might be involved? Perhaps hostility, the researchers suspect, because when they looked to see whether self-reported hostility and sex drive, which had been evaluated in the subjects during their initial assessment, mediated the effects of LH and FSH on recidivism, they found that only hostility—not sex drive—did.Hostility had been evaluated with the Buss-Durkee Hostility Inventory, which measures seven aspects of hostility—irritability, suspicion, negativism, resentment, indirect hostility, verbal hostility, and physical assault. Rapists have scored high on this inventory in the past.If these findings can be confirmed, they “suggest a new area of investigation in the neurobiology of sexual offending,” Bradford and his group suggested.The study had no outside funding. ■“The Role of Central and Peripheral Hormones in Sexual and Violent Recidivism in Sex Offenders” is posted at http://www.jaapl.org/content/40/4/476.full.pdf+html. ISSUES NewArchived

Pattern of male sex hormones in type 2 diabetic patients in Nnewi, South Eastern Nigeria

Background: Type 2 diabetes mellitus has been shown to be associated with certain endocrine disorders in men. We therefore investigated the levels of male sex hormones in serum of patients with type 2 diabetes mellitus (DM2) and non-diabetic controls (NDMC) with a view to establishing the effect of diabetes mellitus on their endocrine system. Methods: One hundred and twenty five male type 2 diabetic subjects and 50 apparently healthy non-diabetic male individuals within the age of 32 - 70 years were recruited into this study. Fasting plasma glucose (FPG), male sex hormones (follicle stimulating hormone (FSH), prolactin, luteinizing hormone (LH), and testosterone), and body mass index (BMI) were determined. Results: The mean value of FPG, FSH and prolactin were significantly higher in diabetic subjects when compared with the NDMC, but there was no significant difference in the levels of LH and BMI. The level of testosterone was significantly lower in diabetics than in NDMC. There was no significant correlation between duration of diabetes and male sex hormones (FSH, LH, Prolactin and Testosterone). Results also showed that male sex hormones, BMI, FPG, are independent of age. Conclusion: This study revealed decreased levels of testosterone with insignificantly high levels of luteinizing hormone which is suggestive of abnormal feedback mechanism in the hypothalamic- pituitary-testicular axis of these diabetic men. The study also revealed a significant raised serum prolactin levels in type 2 diabetic patients without a definitive cause. We therefore, recommend further studies to elucidate the possible underlying mechanisms involved in these abnormalities so that correct strategies for treatment can be employed.

Hormonal, metabolic and clinical profile of Saudi women with polycystic ovary syndrome

Objective: To establish the hormonal, metabolic and clinical profile for Saudi women with polycystic ovary syndrome (PCOS). Design: This is a prospective, cross-sectional study conducted at the University Hospital. All women were seen at the gynecology clinic. One hundred women aged between 18 and 45 years were included in the study; 50 women with polycystic ovary disease (PCOS) comprised the study group and 50 women without PCOS comprised the control group. The hormonal, metabolic and clinical profiles were assessed for both groups. Results: There are significantly higher levels of luteinizing hormone, prolactin, free testosterone dehydroepianosterone sulfate, 17α-hydroxy progesterone and fasting insulin in the study group. There were no differences in the levels of total testosterone, estradiol and cortisone levels between both groups. The levels of follicular stimulating hormone and sex hormone binding globulin were significantly lower in the study group. There were no differences in the blood sugar level, cholesterol, triglycerides and low- and high-density lipoproteins. The womens' ages, body mass index, blood pressure, uterine dimensions and endometrial thickness were similar in both groups. The size of both ovaries was significantly greater in the study group. There were more follicles in the ovaries of the study group. Conclusion: Hormonal profile of Saudi women with PCOS was similar with what is already published in the medical literature. But, despite the fact that Saudi women with and without PCOS are overweight, they do not suffer from raised blood pressure and metabolic syndrome; this may be due to the fact that women included in this study were relatively young and the sample size might be too small to draw effective conclusions.

Increased mean glucose levels in patients with polycystic ovary syndrome and hyperandrogenemia as determined by continuous glucose monitoring

Women with polycystic ovary syndrome are at risk of developing type 2 diabetes mellitus. This study aimed to evaluate the influence of hyperandrogenemia on glucose metabolism in polycystic ovarian syndrome patients. Cohort study. Reproductive Endocrinology Clinic of the Shanghai Sixth People's Hospital. Fifty-three patients were recruited from June 2008 to December 2009, including 28 women with hyperandrogenism and 25 without hyperandrogenemia. Anthropometric parameters, including weight, height, body mass index and waist-to-hip ratio, as well as sex hormones, were measured. An oral glucose tolerance test, including fasting and two hour glucose and insulin levels, was recorded. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance, and patients underwent continuous glucose monitoring. Mean blood glucose level, mean amplitude of glycemic excursion, frequency of glycemic excursion and the percentage of time of hypoglycemia and hyperglycemia during a 48 h period. No differences in age, body mass index, waist-to-hip ratio, fasting and two hour glucose and insulin concentrations were observed between the groups. The hyperandrogenism group had higher levels of luteinizing hormone and dehydroepiandrosterone sulfate (p < 0.05). However, continuous glucose monitoring showed that the minimal blood glucose and mean blood glucose were significantly higher in hyperandrogenemia group (p = 0.004). The percentage of time for hypoglycemia (≤70 mg/dL) was higher in the hyperandrogenemia group (p = 0.002). Polycystic ovarian syndrome patients with hyperandrogenemia had an increased mean glucose value, which may place them at increased risk for developing type 2 diabetes.

Atypical Leydig cell hyperplasia in adult rats with low T and high LH induced by prenatal Di(n-butyl) phthalate exposure.

The present study describes atypical Leydig cell (LC) hyperplasia in 20-week-old Sprague-Dawley rats with low testosterone and high luteinizing hormone levels after prenatal administration of 100 mg/kg/day di(n-butyl) phthalate on days 12 to 21 postconception. Light microscopy revealed LC hyperplasia surrounded by severely degenerated seminiferous tubules. Aggregated LCs had large ovoid nuclei with nucleoli and abundant eosinophilic cytoplasm. Immunohistochemical analysis showed expression of proliferating cell nuclear antigen and vimentin in many hyperplastic LCs. Electron microscopy revealed atypical nuclei, abundant free ribosomes, stripped rough endoplasmic reticulum, intermediate-size filaments, elongated cytoplasmic filopodia, atypical tight junctions, and cilia formations, but smooth endoplasmic reticulum was scarcely observed.

Evaluation of the effects of testosterone and luteinizing hormone on regulation of β-amyloid in male 3xTg-AD mice

During normal aging, men experience a significant decline in testosterone levels and a compensatory elevation in levels of gonadotropin luteinizing hormone (LH). Both low testosterone and elevated LH have been identified as significant risk factors for the development of Alzheimer's disease (AD) in men. It is unclear whether changes in testosterone or LH primarily underlie the relationship with AD, and therefore may be a more suitable therapeutic target. To examine this issue, we compared levels of β-amyloid (Aβ) immunoreactivity in male 3xTg-AD mice under varying experimental conditions associated with relatively low or high levels of testosterone and/or LH. In gonadally intact mice, Aβ accumulation increased after treatment with the gonadotropin‐releasing hormone agonist leuprolide, which inhibits the hypothalamic-pituitary-gonadal (HPG) axis and reduces both testosterone and LH levels. In gonadectomized (GDX) mice with low testosterone and high LH, we also observed increased Aβ levels. Treatment of GDX mice with testosterone significantly reduced Aβ levels. In contrast, leuprolide did not significantly decrease Aβ levels and moreover, inhibited the Aβ-lowering effect of testosterone. Evaluation of hippocampal-dependent behavior revealed parallel findings, with performance in GDX mice improved by testosterone but not leuprolide. These data suggest that Aβ-lowering actions of testosterone are mediated directly by androgen pathways rather than indirectly via regulation of LH and the HPG axis. These findings support the clinical evaluation of androgen therapy in the prevention and perhaps treatment of AD in hypogonadal men.

The effects of water temperature and hormone treatments on circulating LH and ovulation in tench (Tinca tinca)

The effectiveness of three hormone treatments commonly used for artificial reproduction of tench was evaluated under three thermal regimes, with focus on the need for dopamine antagonist. Mature females were divided into nine groups (n = 8) and gradually exposed, over a 24 h period, to three temperature regimes: cold (18.1 ± 0.02 °C), optimal (22.05 ± 0.03 °C), and warm (26.3 ± 0.01 °C). Each temperature regime comprised three experimental groups injected with one of three hormone treatments: carp pituitary extract (CPE; 3 mg kg−1); [D-Arg6, Pro9, NEt]-sGnRH (10 μg kg−1); and [D-Arg6, Pro9, NEt]-sGnRH (10 μg kg−1) + metoclopramide (20 mg kg−1) (combined treatment). No differences were found between ovulation induction (ovulation rate ≥ 75 %) with sGnRHa alone and with the combined treatment; whereas CPE at cold and warm water temperatures was significantly less effective (P < 0.05) than above mentioned treatments. Administration of sGnRHa alone induced a gradual increase in luteinizing hormone (LH) levels with LH peaks close to ovulation, in contrast to the immediate LH surge with high LH levels throughout the entire study observed with the combined treatment under all thermal regimes. LH levels induced by GnRHa alone were significantly lower (P < 0.05) at all temperatures compared to the combined treatment, with the exception of the final sample at 26 °C, when no difference was recorded. Based on these results we recommend the application of sGnRHa without the addition of dopamine antagonist as a reliable method for inducing ovulation in tench under suboptimal temperature conditions.

Luteinizing hormone facilitates angiogenesis in ovarian epithelial tumor cells and metformin inhibits the effect through the mTOR signaling pathway

High levels of gonadotropin are a risk factor for ovarian cancer development. Aberrant gonadotropin levels benefit tumor angiogenesis, but the detailed mechanism is not clear. Therefore, the aim of this study was to investigate the molecular mechanism of high levels of luteinizing hormone (LH) on the promotion of tumor angiogenesis and to outline a feasible therapeutic strategy. Western blotting and immunofluorescence staining were used to determine the effect of LH on VEGF and slit2 expression and examine the signaling pathway involved in regulating the expression of both molecules. Real-time PCR was used to investigate the effect of metformin on LH induction of VEGF and slit2 expression. It was found that 50 mIU/ml LH significantly upregulated VEGF and slit2 expression, and activated the PI3K/AKT-mTOR signaling pathway. However, metformin inhibited the mTOR signaling pathway and further blocked LH-induced VEGF and slit2 expression. In conclusion, high levels of LH promote angiogenesis in ovarian cancer via the PI3K/AKT-mTOR pathway. However, metformin could inhibit tumor angiogenesis by blocking the mTOR signaling pathway.

Polycystic ovary syndrome: brain-derived neurotrophic factor (BDNF) plasma and follicular fluid levels

Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age. Features of PCOS are hyperandrogenism, chronic anovulation and polycystic ovaries on ultrasonography. Follicle development is a complex and carefully orchestrated phenomenon, involving gonadotropins and a rapidly expanding list of other intraovarian regulators, such as brain-derived neurotrophic factor (BDNF). The aim of this study is to evaluate BDNF in plasma and in follicular fluid in women affected by PCOS and in normal menstruating women. In PCOS patients the BDNF levels in plasma and in follicular fluid are higher than values obtained in healthy controls. Therefore we can hypothsize that high levels of luteinizing hormone, probably increase the secretion of BDNF in PCOS patients.