Variation In Hormone Levels Research Articles

Getting a Leg Up on the Competition: The Importance of Osteology in Elite Athletics

We endorse the argument that natural variation in hormone levels, genes, and receptors confounds the attempts of regulatory agencies like the IAAF to distinguish between male and female athletes. W...

The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis.In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10−7M and 10−8M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains.In testes, immunofluorescent reaction for 3β- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1β were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3β and 17β steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 β expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. −90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules.Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.

Unraveling Genes, Hormones, and Breast Cancer

Unraveling Genes, Hormones, and Breast Cancer

CYP3A Variation, Premenopausal Estrone Levels, and Breast Cancer Risk

Epidemiological studies have provided strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women. We measured urinary levels of estrone glucuronide (E1G) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle in 729 healthy premenopausal women. We genotyped 642 single-nucleotide polymorphisms (SNPs) in these women; a single SNP, rs10273424, was further tested for association with the risk of breast cancer using data from 10 551 breast cancer case patients and 17 535 control subjects. All statistical tests were two-sided. rs10273424, which maps approximately 50 kb centromeric to the cytochrome P450 3A (CYP3A) gene cluster at chromosome 7q22.1, was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI] = 27.8% to 15.3% reduction; P = 2.7 × 10(-9)) and a modest reduction in the risk of breast cancer in case patients who were diagnosed at or before age 50 years (odds ratio [OR] = 0.91, 95% CI = 0.83 to 0.99; P = .03) but not in those diagnosed after age 50 years (OR = 1.01, 95% CI = 0.93 to 1.10; P = .82). Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. This association may have wider implications given that the most predominantly expressed CYP3A gene, CYP3A4, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents used in the treatment of breast cancer.

The role of androgens in species recognition and sperm production in Atlantic mollies (Poecilia mexicana)

Much is known about the role of hormones in the regulation of vertebrate mating behavior, including receptivity, and several components of mate choice. Hormones may modulate reproductive behavior in such a way to increase or decrease the individual's motivation, and therefore hormones may be important in mediating behavior associated with reproductive isolation. The mating complex of the all female gynogenetic Amazon mollies, Poecilia formosa, and their parental species (sailfin mollies, P. latipinna, and Atlantic mollies, P. mexicana) is a model system for studying ultimate mechanisms of species recognition. However, proximate mechanisms, such as variation in hormone levels, and the effect of hormones on sperm production have not been extensively examined. We predict that one or more of the sex steroid hormones in teleost fish (11-ketotestosterone (KT), testosterone (T), and estradiol (E)) will play a role in species recognition (during mate choice and/or sperm priming) for Atlantic mollies (the maternal parental species) that are sympatric with Amazon mollies. We sequentially paired male Atlantic mollies with female conspecifics and Amazon mollies and obtained water-borne hormone samples before and after mating for all fish. We measured circulating KT, T, and E from the water samples. Although we did not find an overall KT response to mating with conspecifics as has been found previously in sailfin mollies, male Atlantic mollies that mated more with conspecific females had lower postmating T levels. Additionally, males attempted to mate more with conspecific females that had lower postmating E levels, but attempted to mate more with Amazon mollies that had higher postmating KT levels. We also examined the effect of KT on sperm priming (a mechanism of premating mate choice), and found that KT levels of male Atlantic mollies prior to mating are correlated with the sperm priming response when males were paired with conspecific females, but this correlation was not found when males were paired with Amazon mollies. Our results indicate that male mating behavior is affecting or responding to both male and female hormones, but that the hormones alone are not playing a role in species recognition. Male Atlantic mollies may not discriminate against Amazon mollies as strongly as male sailfin mollies because Amazon mollies resemble their maternal parental species more than their paternal species.

Generalized degrees of freedom and adaptive model selection in linear mixed-effects models

Linear mixed-effects models involve fixed effects, random effects and covariance structures, which require model selection to simplify a model and to enhance its interpretability and predictability. In this article, we develop, in the context of linear mixed-effects models, the generalized degrees of freedom and an adaptive model selection procedure defined by a data-driven model complexity penalty. Numerically, the procedure performs well against its competitors not only in selecting fixed effects but in selecting random effects and covariance structure as well. Theoretically, asymptotic optimality of the proposed methodology is established over a class of information criteria. The proposed methodology is applied to the BioCycle Study, to determine predictors of hormone levels among premenopausal women and to assess variation in hormone levels both between and within women across the menstrual cycle.

Hair cortisol levels track phylogenetic and age related differences in hypothalamic–pituitary–adrenal (HPA) axis activity in non-human primates

Hair has been shown to archive a uniquely time averaged signal of endocrine activity, and holds attractive advantages for both laboratory and field research. Prior research has explored the potential of hair hormone analysis to examine hormone–behavior relationships. To date, no research has focused on the potential of the technique to investigate age-related changes or taxon differences in endocrine function. It is known that non-human primate infants of many taxa exhibit high cortisol levels after parturition, which rapidly decline with age. It has also been shown that hypercortisolism generally characterizes platyrrhine (New World monkey) endocrine function. These endocrine trends have been characterized using cortisol levels determined from serum, plasma, and feces. Here we test whether cortisol levels determined from hair recover similar phylogenetic and age related patterns in endocrine function in non-human primates. In order to test whether hair cortisol reflect infant hypercortisolism with significant age-related decline, hair cortisol levels are measured in samples from wild vervet monkeys ( Chlorocebus aethiops) and captive Guinea baboons ( Papio hamadryas papio), ranging in age from infants through juveniles. Further, in order to test whether platyrrhines exhibit significantly higher hair cortisol levels compared to strepsirrhines and catarrhines, and therefore faithfully recover similar signals as more traditionally used substrates (e.g. serum), hair cortisol levels are quantified in adult female hair samples collected from a broad range of non-human primate taxa. Results confirm that hair cortisol levels accurately reflect known phylogenetic and age related patterns of circulating cortisol levels. Therefore, these results suggest that hair may be an ideal hormone bearing substrate for research focused on the examination of population endocrine profiles, cross-sectional studies of endocrine function and taxon variation in hormone levels, as well as stable behavioral trends.

Frailty in Relation to Variations in Hormone Levels of the Hypothalamic-Pituitary-Testicular Axis in Older Men: Results From the European Male Aging Study

To explore the associations between frailty and reproductive axis hormones (as an important regulatory system) in middle aged and older men. Cross-sectional. The European Male Aging Study. Three thousand two hundred nineteen community-dwelling European men aged 40 to 79. Interviewer-assisted questionnaires to assess physical activity, health status, and mood were administered. Testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in a fasting morning blood sample. Frailty was assessed as an index (FI) according to the number (out of 43 possible) of health deficits (symptoms, signs, and functional impairments). Relationships between FI and hormone levels (as outcomes) were explored using regression models. Mean FI was 0.12 ± 0.11 (range 0-0.67) was highest in the oldest group. After adjustment for confounders, higher levels of FI were significantly associated with lower levels of total T, free T, and DHEAS and higher levels of gonadotropins and SHBG; a 1-standard deviation cross-sectional increase in FI was associated with a regression coefficient of -0.30 nmol/L (95% confidence interval (CI)=-0.53 to -0.07) decrease in total T and 0.66 U/L (95% CI=0.48-0.83) increase in LH. The associations between high FI, high gonadotropins, and well-maintained circulating T suggest that these changes are markers of aging-related disruptions of multiple physiological regulation, of which alterations in pituitary-testicular function represent a sensitive marker rather than an underlying pathogenic mechanism for frailty.

Modification of nitric oxide synthase immunoreactivity in female mouse limbic system during the estrous cycle

Nitric oxide (NO) is a gaseous neuronal messenger, synthesized by the enzyme nitric oxide synthase (NOS), and implicated in the regulation of several physiological and behavioral functions. NO-producing neurons have been localized in numerous regions of the mammalian and non-mammalian central nervous system. In rodents, NOS-immunoreactive neurons and fibers were described in hypothalamic and limbic nuclei belonging to neural circuits implicated in the control of reproductive behavior. Fluctuating levels of estradiol and progesterone during the estrous cycle may induce structural changes in several brain nuclei, where some neurons express estrogen receptors. Various reports indicate that the expression of nNOS is influenced by estrogens in the female. Therefore, to clarify if the nitrergic system is a target for gonadal hormones in physiological conditions, we have investigated the effects of estrous cycle in the expression of nNOS immunoreactivity in different nuclei of the limbic system on two-month-old intact female mice. Changes were observed in the medial preoptic area (significantly higher number in estrus) and in the arcuate nucleus (significantly higher number in proestrus). In the ventrolateral part of the ventromedial nucleus and in the bed nucleus of the stria terminalis no significant changes have been observed. In hippocampus the number of nNOS positive neurons fluctuates during the estrous cycle, reaching its peak during proestrus and metaestrus, and these variations were statistically significant. These results suggest that, in mice, the expression of nNOS in some limbic regions, involved in the control of reproduction and characterized by a large number of estrogen receptors, is under the control of gonadal hormones and may vary according to the short-term variations of hormonal levels that take place during the estrous cycle.? This study has been supported by grants from MURST and University of Torino (SG and GCP).

The Metabolic Phenotype of Prader-Willi Syndrome (PWS) in Childhood: Heightened Insulin Sensitivity Relative to Body Mass Index

Context Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of PWS remain obscure. We compared the fasting levels of various hormones, cytokines, lipids, and liver function tests in 14 PWS patients and 14 OCs with those in 14 age- and gender-matched lean children (LC). We hypothesized that metabolic profiles of children with PWS are comparable with those of LC but different from those of OCs. Results Leptin levels were comparable in PWS patients and OCs, suggesting comparable degrees of adiposity. Glucose levels were comparable among groups. However, fasting insulin concentrations and homeostasis model assessment insulin resistance index were lower in PWS patients than in OCs (P < 0.05) and similar to LC. Moreover, high-density lipoprotein levels were lower and triglycerides higher in OCs (P < 0.05) but not PWS patients. Total adiponectin, high-molecular-weight (HMW) adiponectin and the HMW to total adiponectin ratio were higher in PWS patients (P < 0.05) than in OCs and similar to LC. High-sensitivity C-reactive protein and IL-6 levels were higher in OCs than in PWS patients or LC (P < 0.05). Nevertheless, PAI-1 levels were elevated in both OC and PWS patients. There were no group differences in glucagon-like peptide-1-(7-36)-amide, macrophage chemoattractant protein-1, TNFα, IL-2, IL-8, IL-10, IL-12p40, IL-18, resistin, total or low-density lipoprotein cholesterol, aspartate aminotransferase, or aminotransferase. Conclusions The heightened insulin sensitivity of PWS patients relative to OCs is associated with higher levels of adiponectin and lower levels of high-sensitivity C-reactive protein and IL-6. Future studies will determine whether PWS children are protected from obesity comorbidities such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease.

Individual variation in plasma testosterone levels and its relation to badge size in House Sparrows Passer domesticus: It’s a night-and-day difference

The steroid hormone testosterone (T) plays a central role in the regulation of reproduction in animals. Although seasonal variation in T levels is well-studied, differences between day and night have only been described in relatively few species, and daily within-individual variation has been largely neglected when evaluating the relationship between T and the expression of sexual ornaments or behavior. We measured plasma T levels during day and night in a captive population of House Sparrows, and analyzed their relationship with an important male ornament – badge size. T levels were on average twice as high at night than during daytime. This was true in all seasons, and in both males and females. Disturbance of the birds at night, but not during the day, led to significantly lower T levels, suggesting a rapid drop after an individual wakes up. The relationship between T levels and badge size depended on the time when T was measured. During the breeding season, badge size was strongly positively correlated with night-time, but not with daytime T levels. This suggests that badge size signals information related to an individual’s maximum potential T level such as social dominance. Our study highlights that integrative research on the endocrine control of ornament expression needs to take diel variation in hormone levels into account.

The Metabolic Phenotype of Prader-Willi Syndrome (PWS) in Childhood: Heightened Insulin Sensitivity Relative to Body Mass Index

Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of PWS remain obscure. We compared the fasting levels of various hormones, cytokines, lipids, and liver function tests in 14 PWS patients and 14 OCs with those in 14 age- and gender-matched lean children (LC). We hypothesized that metabolic profiles of children with PWS are comparable with those of LC, but different from those of OCs. Leptin levels were comparable in PWS patients and OCs, suggesting comparable degrees of adiposity. Glucose levels were comparable among groups. However, fasting insulin concentrations and homeostasis model assessment insulin resistance index were lower in PWS patients than in OCs (P < 0.05) and similar to LC. Moreover, high-density lipoprotein levels were lower and triglycerides higher in OCs (P < 0.05) but not PWS patients. Total adiponectin, high-molecular-weight (HMW) adiponectin and the HMW to total adiponectin ratio were higher in PWS patients (P < 0.05) than in OCs and similar to LC. High-sensitivity C-reactive protein and IL-6 levels were higher in OCs than in PWS patients or LC (P < 0.05). Nevertheless, PAI-1 levels were elevated in both OC and PWS patients. There were no group differences in glucagon-like peptide-1, macrophage chemoattractant protein-1, TNFα, IL-2, IL-8, IL-10, IL-12p40, IL-18, resistin, total or low-density lipoprotein cholesterol, aspartate aminotransferase, or alanine aminotransferase. The heightened insulin sensitivity of PWS patients relative to OCs is associated with higher levels of adiponectin and lower levels of high-sensitivity C-reactive protein and IL-6. Future studies will determine whether PWS children are protected from obesity comorbidities such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease.

Challenges and methods in developmental neuroimaging

Even though the developing human mind has been studied for centuries, it is only recently that scientists have gained access to a set of methodological tools that allow examination of the complex relation between children’s thoughts and behavior and the developing and maturing brain. This special issue was inspired by a 3-day interdisciplinary symposium entitled ‘‘Challenges and Methods in Developmental Neuroimaging,’’ held at the Trippenhuis of the Royal Netherlands Academy of Arts and Sciences (KNAW) in Amsterdam in May 2009. We aimed to bring together junior and senior scientists in this field to evaluate whether and how neuroimaging techniques have resulted in greater understanding of the relation between the developing mind, brain, and behavior, and discuss how neuroimaging can increase this understanding in the future. There has been a dramatic increase in the use of brain imaging techniques to investigate the developing mind and brain since the first article using functional MRI (fMRI) with children was published in 1995 [Casey et al., 1995]. A current search for articles using fMRI with children in PubMed results in a count of 634 articles, highlighting how rapidly the field has developed. Despite these advances, the actual mapping of brain activation to mental function still holds several challenges. Scientists in this research area are very enthusiastic about what developing neuroimaging has brought us and can bring us, but also warn against overly simplistic application and interpretation of these methods. Three of the future challenges are highlighted below.

Abstract 1826: Anthropometric characteristics, physical activity and risk of lymphoid neoplasms in a large US cohort

Abstract Body size, height, and physical inactivity are known to alter immune function and have been hypothesized to increase risk of non-Hodgkin lymphoma (NHL). However, results of other studies are inconsistent and whether these relationships vary by histologic subtypes of NHL is not well-documented. Therefore, we examined measures of body size (BMI, adult weight gain, and BMI at age 18), height, physical activity, and sitting time in relation to risk of NHL overall and within the major subtypes (diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and multiple myeloma (MM)) in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a prospective study of cancer incidence and mortality, using information obtained at baseline in 1992. From 1992-2007, 2000 incident NHL cases were identified among 150,189 men and women who were cancer-free at enrollment. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) while adjusting for potential confounders. Obese men and women (BMI &amp;gt; 30) had a 20% higher incidence of all NHL (95% confidence interval (CI) 1.05-1.37) compared to normal weight individuals (BMI 18.5-&amp;lt;25). BMI at age 18 and BMI measured 10-years prior to baseline (in 1982) were also associated with NHL risk (trend p=0.008 and p=0.0003, respectively) in men and women, even after adjustment for baseline BMI. Height was positively associated with overall risk (RR=1.25, 95% CI 1.10-1.43 for sex-specific quintile 5 vs. 1). Associations were similar across all subtypes of NHL examined. Measures of physical activity and sitting time were not associated with risk of NHL or within any specific subtype. These findings suggest that obesity throughout adulthood and greater height may play a role in the etiology of NHL. While more recent obesity may impact immune function or levels of various hormones, height and BMI at age 18 may reflect early-life consequences of nutrition or exposure to growth hormones. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1826.

More Night Than Day — Circadian Rhythms in Polymyalgia Rheumatica and Ankylosing Spondylitis

The circadian rhythm of symptoms in patients with chronic inflammatory diseases is well known. Circadian rhythms could be used to identify targets for time-adapted antiinflammatory therapies, which are administered prior to the flare of cytokine synthesis and inflammatory activity. In recent years, the diurnal variations in rheumatoid arthritis have been described precisely for pain, stiffness, and functional disability, as well as the underlying cyclic variations in hormone levels and cytokine concentrations. This review summarizes the current knowledge on circadian rhythms in other rheumatic diseases, focusing on polymyalgia rheumatica and ankylosing spondylitis.

CLIC5 mutant mice are resistant to diet-induced obesity and exhibit gastric hemorrhaging and increased susceptibility to torpor

Chloride intracellular channel 5 (CLIC5) and other CLIC isoforms have been implicated in a number of biological processes, but their specific functions are poorly understood. The association of CLIC5 with ezrin and the actin cytoskeleton led us to test its possible involvement in gastric acid secretion. Clic5 mutant mice exhibited only a minor reduction in acid secretion, Clic5 mRNA was expressed at only low levels in stomach, and Clic5 mutant parietal cells were ultrastructurally normal, negating the hypothesis that CLIC5 plays a major role in acid secretion. However, the mutants exhibited gastric hemorrhaging in response to fasting, reduced monocytes and granulocytes suggestive of immune dysfunction, behavioral and social disorders suggestive of neurological dysfunction, and evidence of a previously unidentified metabolic defect. Wild-type and mutant mice were maintained on normal and high-fat diets; plasma levels of various hormones, glucose, and lipids were determined; and body composition was studied by quantitative magnetic resonance imaging. Clic5 mutants were lean, hyperphagic, and highly resistant to diet-induced obesity. Plasma insulin and glucose levels were reduced, and leptin levels were very low; however, plasma triglycerides, cholesterol, phospholipids, and fatty acids were normal. Indirect calorimetry revealed increased peripheral metabolism and greater reliance on carbohydrate metabolism. Because Clic5 mutants were unable to maintain energy reserves, they also exhibited increased susceptibility to fasting-induced torpor, as indicated by telemetric measurements showing episodes of reduced body temperature and heart rate. These data reveal a requirement for CLIC5 in the maintenance of normal systemic energy metabolism.

A potential role of male and female androgen in species recognition in a unisexual–bisexual mating complex

Hormones play a critical role in the regulation of vertebrate mating behavior, including receptivity, and several components of mate choice. However, less is known about the role of these chemical messengers in mediating behavior associated with premating reproductive isolation. The bisexual–unisexual mating complex of sailfin mollies, Poecilia latipinna, and Amazon mollies, Poecilia formosa (sexual parasites of sailfins) has been a model system for studying ultimate mechanisms of species recognition. However proximate mechanisms, such as variation in hormone levels, have not been examined. We paired male sailfin mollies with either female conspecifics or Amazon mollies and obtained water-borne hormone samples before and after mating for all fish. We measured 11-ketotestosterone, testosterone, and estradiol from the water samples. As expected from previous studies, males mated with conspecifics more frequently than with Amazon mollies. 11-Ketotestosterone production by males increased when they mated with female sailfin mollies who themselves also showed elevated production of 11-ketotestosterone. This increase in male and female 11-ketotestosterone levels was not seen when males mated with Amazon mollies. This unique endocrine interaction represents a potential proximate mechanism for species recognition by male sailfin mollies. We found no significant change in testosterone or estradiol under these conditions suggesting that a single hormone mediates bidirectional interactions between males and females during courtship.

Host intrinsic determinants and potential consequences of parasite infection in free‐ranging red‐fronted lemurs (Eulemur fulvus rufus)

Parasites and infectious diseases represent ecological forces shaping animal social evolution. Although empirical studies supporting this link abound in various vertebrate orders, both the study of the dynamics and impact of parasite infections and infectious diseases in strepsirrhine primates have received little empirical attention. We conducted a longitudinal parasitological study on four groups of wild red-fronted lemurs (Eulemur fulvus rufus) at Kirindy Forest, Madagascar, during two field seasons in consecutive years to investigate i) the degree of gastrointestinal parasite infection on population and individual levels and ii) factors potentially determining individual infection risk. Using a comprehensive dataset with multiple individually assignable parasite samples as well as information on age, sex, group size, social rank, and endocrine status (fecal androgen and glucocorticoid), we examined parasite infection patterns and host traits that may affect individual infection risk. In addition, we examined whether parasite infection affects mating and reproductive success. Our results indicated high variability in parasite infection on individual and population levels. Time of year and group size was important determinants of variability in parasite infection. Variation in hormone levels was also associated with parasite species richness and parasite infection intensity. Differences in parasite infection between years indicate a potential immune-enhancing function of steroid hormones on nematode infections, which has not been reported before from other vertebrates studied under natural conditions. Male mating and reproductive success were not correlated to any measure of parasite infection, which suggests a nonfunctional role of the parasites we examined in primate sexual selection.

Effects of estrous cycle and xenoestrogens expositions on mice nitric oxide producing system.

Nitric oxide (NO)-containing neurons are widely distributed within the central nervous system, including regions involved in the control of reproduction and sexual behavior. Nitrergic neurons may co-localize with gonadal hormone receptors and gonadal hormones may influence neuronal NO synthase expression in adulthood as well as during development. In rodents, the female, in physiological conditions, is exposed to short-term changes of gonadal hormones levels (estrous cycle). Our studies, performed in mouse hypothalamic and limbic systems, reveal that the expression of neuronal NO synthase may vary according to the rapid variations of hormonal levels that take place during the estrous cycle. This is in accordance with the hypothesis that gonadal hormone activation of NO-cGMP pathway is important for mating behavior. NO-producing system appears particularly sensitive to alterations of endocrine balance during development, as demonstrated by our experiments utilizing perinatal exposure to bisphenol A, an endocrine disrupting chemical. In fact, significant effects were detected in adulthood in the medial preoptic nucleus and in the ventromedial subdivision of the bed nucleus of the stria terminalis. Therefore, alteration of the neuronal NO synthase expression may be one of the causes of the important behavioral alterations observed in bisphenol-exposed animals.

Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice.

BackgroundNitric oxide plays an important role in the regulation of male and female sexual behavior in rodents, and the expression of the nitric oxide synthase (NOS) is influenced by testosterone in the male rat, and by estrogens in the female. We have here quantitatively investigated the distribution of nNOS immunoreactive (ir) neurons in the limbic hypothalamic region of intact female mice sacrificed during different phases of estrous cycle.ResultsChanges were observed in the medial preoptic area (MPA) (significantly higher number in estrus) and in the arcuate nucleus (Arc) (significantly higher number in proestrus). In the ventrolateral part of the ventromedial nucleus (VMHvl) and in the bed nucleus of the stria terminalis (BST) no significant changes have been observed. In addition, by comparing males and females, we observed a stable sex dimorphism (males have a higher number of nNOS-ir cells in comparison to almost all the different phases of the estrous cycle) in the VMHvl and in the BST (when considering only the less intensely stained elements). In the MPA and in the Arc sex differences were detected only comparing some phases of the cycle.ConclusionThese data demonstrate that, in mice, the expression of nNOS in some hypothalamic regions involved in the control of reproduction and characterized by a large number of estrogen receptors is under the control of gonadal hormones and may vary according to the rapid variations of hormonal levels that take place during the estrous cycle.