Photoperiod reverses the effects of estrogens on male aggression via genomic and nongenomic pathways.
Ontology highlight
ABSTRACT:
SUBMITTER: Trainor BC
PROVIDER: S-EPMC1876655 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In three genuses and four species of rodents, housing in winter-like short days (8L:16D) increases male aggressive behavior. In all of these species, males undergo short-day induced regression of the reproductive system. Some studies, however, suggest that the effect of photoperiod on aggression may be independent of reproductive responses. We examined the effects of photoperiod on aggressive behavior in California mice (Peromyscus californicus), which do not display reproductive responsiveness to short days. As expected, short days had no effect on plasma testosterone. Estrogen receptor alpha and estrogen receptor beta immunostaining did not differ in the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, or medial amygdala. However, males housed in short days were significantly more aggressive than males housed in long days. Similar to previous work in beach mice (Peromyscus polionotus), estradiol rapidly increased aggression when male California mice were housed in short days but not when housed in long days. These data suggest that the effects of photoperiod on aggression and estrogen signaling are independent of reproductive responses. The rapid action of estradiol on aggression in short-day mice also suggests that nongenomic mechanisms mediate the effects of estrogens in short days.
| S-EPMC2190085 | biostudies-literature
Project description:BACKGROUND: Sulfation plays an important role both in detoxification and in the control of steroid activity. Studies in rodents have shown that the conversion of dehydroepiandrosterone (DHEA) to DHEA-sulfate is involved in learning and the memory process. METHODS: The effects of a range of plasticizers and related compounds commonly encountered in the environment were evaluated kinetically against human DHEA sulfotransferase (SULT 2A1) and by reverse transcriptase-polymerase chain reaction (RT-PCR) against several enzymes involved in the synthesis of the sulfotransferase cofactor adenosine 3'-phosphate 5'-phosphosulfate (PAPS). RESULTS: We found that several of the chemicals acted as competitive inhibitors of SULT 2A1 (K(i) for 4-tert-octylphenol is 2.8 microM). Additionally, after treatment of TE 671 cells with 0.005-0.5 microM 4-n-octylphenol, bis(2-ethylhexyl)phthalate, and diisodecyl phthalate, real-time RT-PCR showed dose-dependent decreases in the steady-state mRNA levels of cysteine dioxygenase type I, sulfite oxidase, and 3'-phosphate 5'-phosphosulfate synthase I. CONCLUSIONS: These data suggest that environmental contaminants may exert effects on neuronal function both by direct inhibition of sulfotransferase enzymes and by interrupting the supply of PAPS, which has wider implications for endocrine disruption and xenobiotic metabolism.
| S-EPMC2174413 | biostudies-literature
Project description:Vitamin A or retinol is arguably the most multifunctional vitamin in the human body, as it is essential from embryogenesis to adulthood. The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs, and PPAR?/?), polymorphic retinoic acid (RA) response elements, and multiple coregulators. It also involves extranuclear and nontranscriptional effects, such as the activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of several actors of RA signaling. However, vitamin A itself proved recently to be active and RARs to be present in the cytosol to regulate translation and cell plasticity. These new concepts expand the scope of the biologic functions of vitamin A and RA.
| S-EPMC3679380 | biostudies-literature
Project description:Aggressive behavior in our modern, civilized society is often counterproductive and destructive. Identifying specific proteins involved in the disease can serve as therapeutic targets for treating aggression. Here, we found that overexpression of RGS2 in explicitly serotonergic neurons augments male aggression in control mice and rescues male aggression in Rgs2 -/- mice, while anxiety is not affected. The aggressive behavior is directly correlated to the immediate early gene c-fos induction in the dorsal raphe nuclei and ventrolateral part of the ventromedial nucleus hypothalamus, to an increase in spontaneous firing in serotonergic neurons and to a reduction in the modulatory action of Gi/o and Gq/11 coupled 5HT and adrenergic receptors in serotonergic neurons of Rgs2-expressing mice. Collectively, these findings specifically identify that RGS2 expression in serotonergic neurons is sufficient to drive male aggression in mice and as a potential therapeutic target for treating aggression.
| S-EPMC6789038 | biostudies-literature
Project description:Intraspecific male-male aggression, which is important for sexual selection, is regulated by environment, experience and internal states through largely undefined molecular and cellular mechanisms. To understand the basic neural pathway underlying the modulation of this innate behavior, we established a behavioral assay in Drosophila melanogaster and investigated the relationship between sexual experience and aggression. In the presence of mating partners, adult male flies exhibited elevated levels of aggression, which was largely suppressed by prior exposure to females via a sexually dimorphic neural mechanism. The suppression involved the ability of male flies to detect females by contact chemosensation through the pheromone-sensing ion channel ppk29 and was mediated by male-specific GABAergic neurons acting on the GABAA receptor RDL in target cells. Silencing or activating this circuit led to dis-inhibition or elimination of sex-related aggression, respectively. We propose that the GABAergic inhibition represents a critical cellular mechanism that enables prior experience to modulate aggression.
| S-EPMC3995170 | biostudies-literature
Project description:The current study is the first to examine the central nervous processing of aggression chemosignals within men and women by means of chemosensory event-related potential (CSERP) analysis. Axillary sweat was collected from 17 men and 17 women participating in a competitive computer game (aggression condition) and playing a construction game (control condition). Sweat samples were pooled with reference to donor gender and condition, and presented to 23 men and 25 women via a constant flow olfactometer. Ongoing electroencephalogram was recorded from 61 scalp locations, CSERPs (P2, P3-1, P3-2) were analysed and neuronal sources calculated (low-resolution electromagnetic tomography, LORETA). Women, especially, showed larger P3-1 and P3-2 amplitudes in response to male as compared with female aggression signals (all p values < 0.01). The peak activation of this effect was related to activity within the dorsomedial prefrontal cortex (Brodmann area 8). As male aggression commonly targets physical harm, the competence of the human brain to sensitively detect male aggression signals is considered to be highly adaptive. The detection of male aggression signals seems to be of higher importance for women than for men. It is suggested that the processing of male aggression signals in women induces an immediate response selection. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.
| S-EPMC7209929 | biostudies-literature
Project description:How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression.
| S-EPMC5648542 | biostudies-literature
Project description:In many vertebrate species, certain individuals will seek out opportunities for aggression, even in the absence of threat-provoking cues. Although several brain areas have been implicated in the generation of attack in response to social threat, little is known about the neural mechanisms that promote self-initiated or 'voluntary' aggression-seeking when no threat is present. To explore this directly, we utilized an aggression-seeking task in which male mice self-initiated aggression trials to gain brief and repeated access to a weaker male that they could attack. In males that exhibited rapid task learning, we found that the ventrolateral part of the ventromedial hypothalamus (VMHvl), an area with a known role in attack, was essential for aggression-seeking. Using both single-unit electrophysiology and population optical recording, we found that VMHvl neurons became active during aggression-seeking and that their activity tracked changes in task learning and extinction. Inactivation of the VMHvl reduced aggression-seeking behavior, whereas optogenetic stimulation of the VMHvl accelerated moment-to-moment aggression-seeking and intensified future attack. These data demonstrate that the VMHvl can mediate both acute attack and flexible seeking actions that precede attack.
| S-EPMC4853470 | biostudies-literature
Project description:Thyroid hormone (TH) levels increase rapidly during the prepubertal growth period in mice, and this change is necessary for endochondral ossification of the epiphyses. This effect of TH on epiphyseal chondrocyte hypertrophy is mediated via TR?1. In addition to its traditional genomic signaling role as a transcription factor, TR?1 can also exert nongenomic effects by interacting with other signaling molecules such as PI3K. To investigate the role of nongenomic TR?1 signaling in endochondral ossification, we evaluated the skeletal phenotype of TR?147F mutant mice which exhibit a normal genomic response of TR?1 to TH, but the nongenomic response through the PI3K pathway is impaired. Using microCT, we found that 13-week-old TR?147F mice had significantly less trabecular bone mass at three sites. Histomorphometric analyses revealed that mineralizing surface to bone surface and BFR/BS were reduced in the mutant mice. Mechanistically, we found that activation of TR? increased Alp and Osx expression in control but not TR?147F osteoblasts. Since canonical ?-catenin signaling has been implicated in mediating nongenomic TR?-PI3K signaling, we evaluated the effect of TR?1 activation on ?-catenin target gene expression in MC3T3-E1 pre-osteoblasts. We found that ?-catenin target genes were increased, suggesting that nongenomic TR?1-PI3K pathway modulation of ?-catenin signaling may mediate TR?1 effects on osteoblast differentiation. Together, these results suggest that TH acting through TR?1 regulates endochondral ossification in part via nongenomic signaling in mice. Further investigation of this nongenomic mechanism of TR?1 signaling could lead to novel therapeutic targets for treatment and prevention of osteoporosis.
| S-EPMC6685746 | biostudies-literature
Project description:Background: Estrogens are a prime risk factor for breast cancer, yet their causal relation to tumor formation remains uncertain. A recent study of 560 breast cancers identified 82 genes with 916 point mutations as drivers in the genesis of this malignancy. Because estrogens play a major role in breast cancer development and are also known to regulate the expression of numerous genes, we hypothesize that the 82 driver genes are likely to be influenced by estrogens, such as 17ß-estradiol (E2), and the estrogen receptor ESR1 (ER?). Because different types of tumors are characterized by unique sets of cancer driver genes, we also argue that the fraction of driver genes regulated by E2-ESR1 is lower in malignancies not associated with estrogens, e.g., acute myeloid leukemia (AML).Methods: We performed a literature search of each driver gene to determine its E2-ESR1 regulation.Results: Fifty-three of the 82 driver genes (64.6%) identified in breast cancers showed evidence of E2-ESR1 regulation. In contrast, only 19 of 54 mutated driver genes (35.2%) identified in AML were linked to E2-ESR1. Among the 916 driver mutations found in breast cancers, 813 (88.8%) were linked to E2-ESR1 compared with 2,046 of 3,833 in AML (53.4%).Conclusions: Risk assessment revealed that mutations in estrogen-regulated genes are much more likely to be associated with elevated breast cancer risk, while mutations in unregulated genes are more likely to be associated with AML.Impact: These results increase the plausibility that estrogens promote breast cancer development. Cancer Epidemiol Biomarkers Prev; 27(8); 899-907. ©2018 AACR.
| S-EPMC6072561 | biostudies-literature