Plasma LH Levels Research Articles

Leptin and leptin-receptor polymorphisms in fertile and infertile men

ABSTRACTThe association of leptin (LEP) -2548G/A and/or leptin receptor (LEPR) Gln223Arg polymorphisms with male infertility and plasma FSH, LH, and testosterone (T) levels was examined. The genotypes and allele frequency distributions of LEP -2548G/A and LEPR Gln223Arg polymorphisms were investigated in 150 fertile and 150 infertile men by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Also, plasma levels of FSH, LH, and T were measured using commercial ELISA kits. Frequencies of AA, AG and GG genotypes of LEP-2548G/A polymorphism were statistically different in fertile and infertile men (p=0.012). The AG genotype showed a protective effect which could decrease risk of male infertility about 3 fold (p = 0.004). We did not observe any differences in frequencies of LEPR Gln223Arg alleles and genotypes between groups (p > 0.05). Sperm counts from infertile men with the AG and GG genotypes of the LEP polymorphism were significantly higher than AA genotype (p<0.05). Moreover, infertile men who carried the RR genotype of LEPR showed a statistically higher percentage of sperm with progressive motility than individuals with other genotypes (p = 0.004). There was no correlation between different combinations of LEP and LEPR genotypes and LH, FSH, and T levels (p > 0.05). Our study suggests that the LEP -2548G/A polymorphism may play a role in male fertility and the AG genotype may have a protective effect through increasing sperm counts. The distribution of genotypes of LEP -2548G/A polymorphism are different in fertile and infertile males and may be a useful tool in evaluation of male infertility.Abbreviations: LEP: leptin; LEPR: leptin receptor; T: testosterone; FSH: follicle-stimulating hormone; LH: luteinizing hormone

Pulsatile gonadotropin-releasing hormone therapy in persistent amenorrheic weight-recovered anorexia nervosa patients

To compare hormonal and clinical responses to GnRH pulsatile treatment in weight-recovered anorexia nervosa patients (Rec-AN) with persistent functional hypothalamic amenorrhea (HA) vs. in patients with secondary and primary HA. Retrospective, observational, ambulatory study. University hospital. Forty-one women: 19 Rec-AN (body mass index >18.5kg/m2 without menses recovery), 15 secondary HA without any eating disorders patients (SHA), and 7 primary HA patients (PHA). Gonadotropin-releasing hormone pulsatile therapy. Baseline E2, LH, and P plasma levels and their changes during induction cycles; ovulation, follicular recruitment, and pregnancies. The Rec-AN group displayed higher basal E2 and LH plasma levels after GnRH injection compared with SHA and PHA. Higher E2 and LH levels were observed during induction cycles in Rec-AN compared with SHA and PHA. Follicular recruitment was higher in Rec-AN. The ovulation rate was higher in Rec-AN compared with PHA but similar to SHA. This study showed increased gonadal status and higher E2 response to pulsatile GnRH therapy in persistent amenorrheic weight-recovered AN compared with HA from other causes. It suggests that their individual set-point of body weight allowing a fully functional gonadal axis is not reached yet. Specific factors of gonadal inertia in Rec-AN still remain unclear.

Testicular Steroidogenesis and Locomotor Activity Are Regulated by Gonadotropin-Inhibitory Hormone in Male European Sea Bass.

Gonadotropin-inhibitory hormone (GnIH) is a neurohormone that suppresses reproduction by acting at both the brain and pituitary levels. In addition to the brain, GnIH may also be produced in gonads and can regulate steroidogenesis and gametogenesis. However, the function of GnIH in gonadal physiology has received little attention in fish. The main objective of this study was to evaluate the effects of peripheral sbGnih-1 and sbGnih-2 implants on gonadal development and steroidogenesis during the reproductive cycle of male sea bass (Dicentrarchus labrax). Both Gnihs decreased testosterone (T) and 11-ketotestosterone (11-KT) plasma levels in November and December (early- and mid-spermatogenesis) but did not affect plasma levels of the progestin 17,20β-dihydroxy-4-pregnen-3-one (DHP). In February (spermiation), fish treated with sbGnih-1 and sbGnih-2 exhibited testicles with abundant type A spermatogonia and partial spermatogenesis. In addition, we determined the effects of peripheral Gnih implants on plasma follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) levels, as well as on brain and pituitary expression of the main reproductive hormone genes and their receptors during the spermiation period (February). Treatment with sbGnih-2 increased brain gnrh2, gnih, kiss1r and gnihr transcript levels. Whereas, both Gnihs decreased lhbeta expression and plasma Lh levels, and sbGnih-1 reduced plasmatic Fsh. Finally, through behavioral recording we showed that Gnih implanted animals exhibited a significant increase in diurnal activity from late spermatogenic to early spermiogenic stages. Our results indicate that Gnih may regulate the reproductive axis of sea bass acting not only on brain and pituitary hormones but also on gonadal physiology and behavior.

An evaluation of multiplex bead-based analysis of cytokines and soluble proteins in archived lithium heparin plasma, EDTA plasma and serum samples

Objective: To assess the usability of archived plasma and serum by multiplex (Luminex) analysis of circulating proteins (analytes) by evaluating the day to day variation, the effect of several freeze-thaw cycles, and the influence of the media and choice of anticoagulant.Methods: Nineteen analytes in plasma and serum from 86 head and neck cancer patients and 33 controls were evaluated: EGFR, leptin, OPN, VEGFR-1, VEGFR-2, IL-2, IL-13, PDGF-bb, TNF, PAI-1, SDF-1a, IL-4, IL-6, IL-8, eotaxin, G-CSF, VEGF, GRO-a, and HGF.Results: The correlation between measurements of the same samples analyzed on different dates was reasonable. However, samples run on different dates could exhibit different absolute values. The 75th percentile of the fold differences for samples run on different dates was 2.2. No significant difference was found between one and four freeze-thaw cycles (except for HGF), and the correlation was high. We found significant differences in mean concentrations of the majority of analytes in different media and with different anticoagulants. Only the following analytes did not show difference in mean concentrations: EDTA plasma vs. serum: leptin and VEGFR-2, LH plasma vs. serum: IL-2, IL-13, and VEGF, LH plasma levels vs. EDTA plasma: IL-2 and IL-4.Conclusion: Stored serum, LH plasma, and EDTA plasma from clinical trials can be used for analysis of circulating cytokines and proteins. Variations in measurements occur, but are within reasonable ranges. The optimal type of media depends on the analytes, as different analytes have low number of measurements below the lower limit of quantification and higher dynamic ranges in different media.

Progesterone-induced amplification and advancement of GnRH/LH surges are associated with changes in kisspeptin system in preoptic area of estradiol-primed female rats

The time course effects of ovarian steroids on kisspeptin and GnRH/LH systems is not totally clarified. We investigated the temporal relationship among kisspeptin and GnRH mRNA and kisspeptin content in the preoptic area (POA), GnRH content and release in the medial basal hypothalamus (MBH) and plasma LH levels under different steroid treatments. Ovariectomized rats treated with oil (OVOO), oil plus single dose of estradiol (OVOE), oil plus single dose of progesterone (OVOP), estradiol for 3 days plus oil (OVEO) or estradiol for 3 days plus progesterone (OVEP) were hourly decapitated from 10:00 to 17:00 or had the MBH microdialyzed from 09:00 to 19:00. Estradiol and progesterone acutely increased POA kisspeptin content without altering POA kisspeptin mRNA levels. Short-term exposure to both hormones stimulated MBH GnRH content, although no GnRH/LH surges had occurred. Chronic estradiol-treatment increased both kisspeptin mRNA levels and content in the POA, demonstrating that long exposure to estradiol is required to activate the whole kisspeptin synthesis machinery. This was followed by the peak in the GnRH/LH release. In estradiol-primed rats, progesterone further increased POA kisspeptin content, amplified and advanced GnRH/LH surges, with no additional change on POA kisspeptin mRNA. The data show an estradiol-induced temporal association between kisspeptin increase in the POA and GnRH/LH surges. Interestingly, the classic action of progesterone in amplifying and accelerating the GnRH/LH surges seems to occur by a mechanism which involves POA kisspeptin system.

The Methylcytosine Dioxygenase Ten-Eleven Translocase-2 (tet2) Enables Elevated GnRH Gene Expression and Maintenance of Male Reproductive Function.

Reproduction depends on the establishment and maintenance of elevated GnRH neurosecretion. The elevation of primate GnRH release is accompanied by epigenetic changes. Specifically, cytosine residues within the GnRH gene promoter are actively demethylated, whereas GnRH mRNA levels and peptide release rise. Whether active DNA demethylation has an impact on GnRH neuron development and consequently reproductive function remains unknown. In this study, we investigated whether ten-eleven translocation (tet) enzymes, which initiate the process of active DNA demethylation, influence neuronal function and reproduction. We found that tet2 expression increases with age in the developing mouse preoptic area-hypothalamus and is substantially higher in a mature (GT1-7) than an immature (GN11) GnRH cell line. GnRH mRNA levels and mean GnRH peptide release elevated after overexpression of tet2 in GN11 cells, whereas CRISPR/cas9-mediated knockdown of tet2 in GT1-7 cells led to a significant decline in GnRH expression. Manipulations of tet2 expression altered tet2 genome binding and histone 3 lysine 4 trimethylation abundance at the GnRH promoter. Mice with selective disruption of tet2 in GnRH neurons (GnRH-specific tet2 knockout mice) exhibited no sign of altered pubertal timing in either sex, although plasma LH levels were significantly lower, and fecundity was altered specifically in adult male GnRH-specific tet2 knockout animals, indicating that tet2 may participate in the maintenance GnRH neuronal function. Exposure to bisphenol A, an environmental contaminant that alters GnRH neuron activity, caused a shift in tet2 subcellular localization and a decrease in histone 3 lysine 4 trimethylation abundance at the GnRH promoter. Finally, evaluation of tet2 protein interactions in GT1-7 cells suggests that the influence of tet2 on neuronal function are not limited to nuclear mechanisms but could depend on mitochondrial function, and RNA metabolism. Together, these studies implicate tet2 in the maintenance of GnRH neuronal function and neuroendocrine control of male reproduction.

Prospective study of histological and endocrine parameters of gonadal function in boys with cryptorchidism

A transient increase in gonadotropins and testosterone during mini-puberty causes gonocytes to differentiate into Ad spermatogonia, which establish male germ cell memory and male-specific DNA methylation pathways. Over half of patients with unilateral cryptorchidism and the majority of patients with bilateral cryptorchidism display an abnormal spermiogram, which indicates that unilateral cryptorchidism is a bilateral disease; therefore, it represents a serious andrological problem. The aim of this study was to evaluate relationships between hormonal parameters and testicular biopsy findings in boys with cryptorchidism. Seventy-one boys (median age 15 months; range 7-65 months) who underwent orchidopexy (24% had bilateral cryptorchidism) were tested for serum LH, FSH, and inhibin B. With ipsilateral testis biopsy histology, we determined the tubular fertility index (TFI), Ad spermatogonia counts, and Ad/tubular index (Ad/T). We compared age groups (<18 vs. >18 months old); groups with and without Ad spermatogonia; groups with unilateral and bilateral cryptorchidism; and extreme groups with high infertility risk (HIR; n=12; TFI <0.2; Ad/T=0) and low infertility risk (LIR; n=9; TFI >0.9; Ad/T>0.02). Of the specimens, 38% had no Ad spermatogonia. Age was significantly negatively correlated with TFI and Ad/T, but positively correlated with FSH. Median LH values were significantly higher in LIR than in HIR groups. Unilateral and bilateral cryptorchidism showed similarTFI, Ad/T, and hormone concentrations. The areas under ROC curves for FSH, LH, and inhibin B(0.66,0.601, and 0.599, respectively) showed low diagnostic value for predicting HIR (no Ad spermatogonia). Our observation of lower plasma LH levels in the group with the most pronounced testicular pathology was the opposite of what we would have expected if testicular pathological changes were caused by a primary gonadal defect. Therefore, low plasma LH levels in the HIR group confirmed the notion that this group of patients with cryptorchidism had hypogonadotropic hypogonadism. The estimated incidence of defective mini-puberty in boys with cryptorchidism could be as high as 50%. Testicular biopsies from boys with cryptorchidism lacked Ad spermatogonia. Fertility parameters worsened with age. Significantly lower basal LH in the HIR group indicated hypogonadotropic hypogonadism. Serum hormone levels could not predict histological biopsy findings.

Kisspeptin in the medial amygdala and sexual behavior in male rats

The medial amygdala (MeA) is crucial for sexual behavior; kisspeptin (Kiss1) also plays a role in sexual function. Kisspeptin receptor (Kiss1r) knockout mice display no sexual behavior. Recently Kiss1 and Kiss1r have been discovered in the posterodorsal subnucleus of the medial amygdala (MePD). We hypothesised that Kiss1 in the MePD may have an influence on male sexual behavior. To test this we bilaterally cannulated the MePD and infused kisspeptin-10 in male rats. This caused the rats to have multiple erections, an effect specific to Kiss1 receptor activation, because Kiss1r antagonism blocked the erectile response. When Kiss1 was infused into the lateral cerebroventricle, there were no observed erections. We also measured the plasma levels of LH when Kiss1 is infused into the MePD or lateral cerebroventricle; Kiss1 increased plasma LH to comparable levels when infused into both sites. We conclude that Kiss1 has a role in male sexual behavior, which is specific to the MePD.

Gonadotropin Inhibitory Hormone Down-Regulates the Brain-Pituitary Reproductive Axis of Male European Sea Bass (Dicentrarchus labrax).

Gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin synthesis and release from the pituitary of birds and mammals. However, the physiological role of orthologous GnIH peptides on the reproductive axis of fish is still uncertain, and their actions on the main neuroendocrine systems controlling reproduction (i.e., GnRHs, kisspeptins) have received little attention. In a recent study performed in the European sea bass, we cloned a cDNA encoding a precursor polypeptide that contained C-terminal MPMRFamide (sbGnIH-1) and MPQRFamide (sbGnIH-2) peptide sequences, developed a specific antiserum against sbGnIH-2, and characterized its central and pituitary GnIH projections in this species. In this study, we analyzed the effects of intracerebroventricular injection of sbGnIH-1 and sbGnIH-2 on brain and pituitary expression of reproductive hormone genes (gnrh1, gnrh2, gnrh3, kiss1, kiss2, gnih, lhbeta, fshbeta), and their receptors (gnrhr II-1a, gnrhr II-2b, kiss1r, kiss2r, and gnihr) as well as on plasma Fsh and Lh levels. In addition, we determined the effects of GnIH on pituitary somatotropin (Gh) expression. The results obtained revealed the inhibitory role of sbGnIH-2 on brain gnrh2, kiss1, kiss2, kiss1r, gnih, and gnihr transcripts and on pituitary fshbeta, lhbeta, gh, and gnrhr-II-1a expression, whereas sbGnIH-1 only down-regulated brain gnrh1 expression. However, at different doses, central administration of both sbGnIH-1 and sbGnIH-2 decreased Lh plasma levels. Our work represents the first study reporting the effects of centrally administered GnIH in fish and provides evidence of the differential actions of sbGnIH-1 and sbGnIH-2 on the reproductive axis of sea bass, the main inhibitory role being exerted by the sbGnIH-2 peptide.

Apoptosis of Sertoli cells after conditional ablation of murine double minute 2 (Mdm2) gene is p53-dependent and results in male sterility.

Beside its well-documented role in carcinogenesis, the function of p53 family has been more recently revealed in development and female reproduction, but it is still poorly documented in male reproduction. We specifically tested this possibility by ablating Mdm2, an E3 ligase that regulates p53 protein stability and transactivation function, specifically in Sertoli cells (SCs) using the AMH-Cre line and created the new SC-Mdm2−/− line. Heterozygous SC-Mdm2−/+ adult males were fertile, but SC-Mdm2−/− males were infertile and exhibited: a shorter ano-genital distance, an extra duct along the vas deferens that presents a uterus-like morphology, degenerated testes with no organized seminiferous tubules and a complete loss of differentiated germ cells. In adults, testosterone levels as well as StAR, P450c17 (Cyp17a1) and P450scc (Cyp11a1) mRNA levels decreased significantly, and both plasma LH and FSH levels increased. A detailed investigation of testicular development indicated that the phenotype arose during fetal life, with SC-Mdm2−/− testes being much smaller at birth. Interestingly, Leydig cells remained present until adulthood and fetal germ cells abnormally initiated meiosis. Inactivation of Mdm2 in SCs triggered p53 activation and apoptosis as early as 15.5 days post conception with significant increase in apoptotic SCs. Importantly, testis development occurred normally in SC-Mdm2−/− lacking p53 mice (SC-Mdm2−/−p53−/−) and accordingly, these mice were fertile indicating that the aforementioned phenotypes are entirely p53-dependent. These data not only highlight the importance of keeping p53 in check for proper testicular development and male fertility but also certify the critical role of SCs in the maintenance of meiotic repression.

Plasma levels of follicle-stimulating and luteinizing hormones during the reproductive cycle of wild and cultured Senegalese sole (Solea senegalensis)

The intensive culture of the Senegalese sole (Solea senegalensis) is hampered by the low or null fertilization rates exhibited by the first generation (F1) of reared males. To investigate the regulation of the reproductive processes in this species by the pituitary gonadotropins follicle-stimulating and luteinizing hormones (Fsh and Lh, respectively), we developed a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for Lh measurements. Quantification of the Fsh and Lh plasma levels in cultured sole using the Lh ELISA developed here, and a previously developed ELISA for Fsh, indicated that in both males and females circulating Fsh steadily increased during autumn and winter and prior to the major spawning in spring, whereas an Lh surge occurred specifically during spawning. The increase in Fsh was associated with a rise of plasma levels of the steroid hormones testosterone (T), 11-ketotestosterone (11-KT) and estradiol-17β (E2), but that of Lh was concomitant with a strong decline of the levels of E2 in females and of 11-KT in males, possibly reflecting a rapid steroidogenic shift promoting the final maturation of gametes. Comparison of the plasma levels of gonadotropins and steroids between wild and F1 fish during autumn and spring revealed that F1 males showed significantly lower plasma Lh titres compared to wild males, whereas the levels of T and 11-KT were similar or more elevated in the F1 fish. These data suggest that an impaired Lh secretion during spawning, and perhaps altered Lh-mediated mechanisms in the testis, may be underlying causes for the low reproductive performance of Senegalese sole F1 males.

Influence of tidal cycles on the endocrine control of reproductive activity in common snook (Centropomus undecimalis)

The aim of our study was to confirm the role of tidal pattern on the coordination of oocyte maturation and spawning in common snook Centropomus undecimalis. To do so, we studied oocyte maturation during the spawning season in relation to the tidal pattern in both males and females by means of histology and hormonal profiling along the pituitary–gonadal axis. Plasma LH levels, as well as transcript levels of gonadotropin genes (fshβ and lhβ) from the pituitaries of sexually mature male and female common snook were analyzed using a heterologous ELISA and quantitative RT-PCR, respectively. The fshβ and lhβ cDNAs were isolated and phylogenetic analysis of the deduced amino acid sequences revealed strong identity with other teleosts (75–90%). A strong link was found between tide and follicular development irrespective of the time of the day: female snook sampled on the rising tide were all found to have oocytes in the Secondary Growth Stage whereas females sampled at high tide or on the falling tide had oocytes in the later stages of maturation and ovulation. In addition, LH plasma and mRNA levels of fshβ and lhβ increased during the later stages of vitellogenesis peaking at ovulation in females. Plasma estradiol and testosterone significantly increased in late vitellogenesis (Secondary Growth Stage) and oocyte maturation (Eccentric Germinal Vesicle Step) respectively. Among male common snook sampled, no correlation was identified between tide and gonadal development. In addition, lhβ mRNA expression in males peaked at the mid germinal epithelium stage as for testosterone and 11-KT in the blood while fshβ expression and plasma LH levels peaked at late germinal epithelium stage. This study confirms the role played by tidal cycle on the entrainment of the later stages of oogenesis of common snook and provides a better understanding of the link between environmental and endocrine control of reproduction in this species.

Blockade of AT1 receptor of Angiotensin II reduces the number of antral follicles in female rats with obesity induced by cafeteria diet

To evaluate the follicular development of female Wistar rats with obesity induced by the cafeteria diet, submitted to the administration of losartan (LOS), an antagonist of the AT1 receptor of Angiotensin II. At weaning (21 days of age), female Wistar rats were randomly divided, into two groups: control (CTL) that received standard chow and cafeteria (CAF) that received a cafeteria diet, a highly palatable and highly caloric diet. At 70 days of age, at the beginning of the reproductive age, animals of the CAF group were subdivided into two groups (n = 15/group): CAF, that received water, and CAF+LOS, that received LOS for 30 days. The CTL group also received water by gavage. At 100 days of age, the animals were euthanized and body weight (BW) as well as the retroperitoneal, perigonadal and subcutaneous fat weights were analyzed. The right ovaries were isolated for counting the number of primary, secondary, antral and mature follicles. Plasma levels of FSH, LH, prolactin and progesterone hormones were analyzed. The results were expressed as mean ± standard error of the mean. Data were analyzed statistically by one-way ANOVA followed by the Newman-Keuls post-test (p < 0.05). BW and fat weight, as well as the number of antral follicles, were higher in the CAF group compared to the CTL group. However, FSH and LH levels were lower in CAF animals compared to CTL animals. LOS administration attenuated the reduction of FSH and LH levels. Progesterone and PRL levels were similar among groups. LOS could improve follicular development in obese females and could be used as an adjunctive drug in the treatment of infertility associated with obesity.

Effect of dietary n−3 LC-PUFAs on plasma vitellogenin, sex steroids, and ovarian steroidogenesis during vitellogenesis in female silver pomfret (Pampus argenteus) broodstock

We investigated the effects of dietary n − 3 LC-PUFAs on plasma vitellogenin (Vtg), sex steroids levels and ovarian steroidogenesis during vitellogenesis in female silver pomfret (Pampus argenteus) broodstock. Broodstock were fed four iso-nitrogenous, iso-energetic, and iso-lipidic experimental diets for 185 d: FO (100% fish oil), FSO (70% fish oil and 30% soybean oil), SFO (30% fish oil and 70% soybean oil), and SO (100% soybean oil) with n − 3 LC-PUFA levels of 5.18, 4.01, 3.02, and 2.22%, respectively. The results revealed that plasma FSH levels increased at vitellogenesis (P < 0.05) and slightly decreased at post-vitellogenesis in all four groups. However, plasma LH levels continuously increased during vitellogenesis and significantly increased at post-vitellogenesis (P < 0.05). The FO and FSO groups had significantly higher FSH and LH levels than the SO group at vitellogenesis and post-vitellogenesis. Plasma E2 and T levels continuously increased during vitellogenesis in all four groups. However, the SO group had the lowest plasma E2 and T levels during vitellogenesis. Plasma Vtg levels significantly increased at vitellogenesis and post-vitellogenesis (P < 0.05). FO and FSO had significantly higher Vtg levels than SO (P < 0.05) during vitellogenesis. Cyp19α1α and erα expression levels significantly increased at vitellogenesis and post-vitellogenesis (P < 0.05), with no significant differences between the vitellogenesis and post-vitellogenesis, except in the SO group. Cyp19α1α and erα expression levels decreased in SO at vitellogenesis. In conclusion, dietary n − 3 LC-PUFAs affect ovarian steroidogenesis in silver pomfret by altering plasma FSH and LH levels and ovarian Cyp19α1α gene expression levels during vitellogenesis. High dietary n − 3 LC-PUFAs promote ovarian development in silver pomfret, by increasing E2 secretion and Vtg synthesis.

Molecular characterization of three gonadotropin subunits and their expression patterns during ovarian maturation in Cynoglossus semilaevis.

The endocrine regulation of reproduction in a multiple spawning flatfish with an ovary of asynchronous development remains largely unknown. The objectives of this study were to monitor changes in mRNA expression patterns of three gonadotropin hormone (GTH) subunits (FSHβ, LHβ and CGα) and plasma GTH levels during ovarian maturation of half-smooth tongue sole Cynoglossus semilaevis. Cloning and sequence analysis revealed that the cDNAs of FSHβ, LHβ and CGα were 541, 670 and 685 bp in length, and encode for peptides of 130, 158 and 127 amino acids, respectively. The number of cysteine residues and potential N-linked glycosylation sites of the flatfish GTHs were conserved among teleosts. However, the primary structure of GTHs in Pleuronectiformes appeared to be highly divergent. The FSHβ transcriptional level in the pituitary remained high during the vitellogenic stage while plasma levels of FSH peaked and oocyte development was stimulated. The LHβ expression in the pituitary and ovary reached the maximum level during oocyte maturation stages when the plasma levels of LH peaked. The brain GTHs were expressed at the different ovarian stages. These results suggested that FSH and LH may simultaneously regulate ovarian development and maturation through the brain-pituitary-ovary axis endocrine system in tongue sole.

Report on the two‐phase public consultation on the draft EFSA scientific opinion on bisphenol A (BPA)

Report on the two‐phase public consultation on the draft EFSA scientific opinion on bisphenol A (BPA)

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels

BackgroundAggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70mg/dL. MethodsThe study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. ResultsReplacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. ConclusionsOur results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy.

Direct Regulation of Gonadotropin Release by Neurokinin B in Tilapia (Oreochromis niloticus)

Neurokinin B (NKB) was recently identified as a key regulator of reproduction in mammals and fish. Fish were found to possess a specific novel neurokinin termed NKF. To study the role of NKB/NKF in the regulation of fish reproduction and to investigate the role of NKB/NKF and their receptors in the piscine pituitary, we have identified the NKB/tachikinin 3 receptor (tac3r) system in tilapia. Bioinformatics and phylogenetic analyses have demonstrated that the tilapia holds 1 putative tac3 gene and 2 NKB receptor genes (tac3ra and tac3rb) that clustered with other piscine Tac3 and NKB receptor lineages. Furthermore, we found that in African cichlids, NKB peptides differ from other vertebrate NKBs in their C-terminal sequence, possessing isoleucine instead of valine as the X in the NKB FXGLM-NH2-terminal consensus sequence. Signal transduction analysis demonstrated that tilapia NKB (tiNKB), tiNKF, and human NKB activated both CRE-luc and SRE-luc transcriptional activity of both tilapia and human NKB receptors. Two hours after ip injection of tiNKB, the plasma levels of both FSH and LH were increased, whereas tiNKF was more effective in increasing LH levels. However, tiNKB was more effective than tiNKF in increasing both FSH and LH from tilapia pituitary dispersed cells. Using in situ hybridization and fluorescent immunohistochemistry, we have shown that LH cells possess tac3, tac3ra, and tac3rb mRNAs, whereas FSH cells possess mainly tac3rb and tac3ra and tac3 to a much lesser extent. These results suggest that the members of the NKB/tac3r system may serve as paracrine/autocrine regulators of gonadotropin release in fish pituitary.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury

Introduction: Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients.Methods: The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated.Results: At least one hormonal level abnormality was demonstrated in 3.6–73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8–16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9–16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality.Conclusion: The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Maternal sympathetic stress impairs follicular development and puberty of the offspring.

Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural- or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 °C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat.