Effects of aggressive encounters on plasma corticosteroid-binding globulin and its ligands in white-crowned sparrows.

in Hormones & Behavior (2009), 56(3), 339-47

In birds, corticosteroid-binding globulin (CBG) binds corticosterone, progesterone and testosterone. The concentration of each ligand can alter the binding of the other ligands through competitive ... [more ▼]

In birds, corticosteroid-binding globulin (CBG) binds corticosterone, progesterone and testosterone. The concentration of each ligand can alter the binding of the other ligands through competitive interactions. Thus, an increase in corticosterone or progesterone may displace testosterone bound to CBG, leading to an increase in bioactive free testosterone levels without affecting total testosterone levels in the circulation. Aggressive interactions increase plasma total testosterone levels in some birds but not in others. Here, we tested the hypothesis that aggressive encounters in the late breeding season would not increase total testosterone levels in plasma, but would alter CBG, total corticosterone or total progesterone levels in such a way as to modify the number of available binding sites and therefore occupancy by testosterone. A marked decrease in CBG occupancy by testosterone would indirectly suggest an increase in free testosterone levels in plasma. Wild male white-crowned sparrows were exposed to a simulated territorial intrusion (STI) or control for 30 min. Subjects were then caught and bled. We measured CBG using a ligand-binding assay and corticosterone, progesterone and testosterone using highly sensitive radioimmunoassays. STI significantly increased aggressive behaviors but did not affect plasma total testosterone levels. STI significantly increased plasma CBG and total corticosterone levels and decreased plasma total progesterone levels. We predict that CBG occupancy by corticosterone will increase slightly following an aggressive encounter. However, this small change is unlikely to increase free testosterone levels, because of the large number of seemingly unoccupied CBG binding sites in these subjects. [less ▲]

Estradiol, a key endocrine signal in the sexual differentiation and activation of reproductive behavior in quail.

in Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology (2009), 311(5), 323-45

In Japanese quail, estrogen's effects on sexual behavior can be divided into three classes based on the underlying mechanisms and time-course of action and release. During embryonic life, the embryonic ... [more ▼]

In Japanese quail, estrogen's effects on sexual behavior can be divided into three classes based on the underlying mechanisms and time-course of action and release. During embryonic life, the embryonic ovary secretes large amounts of estrogens. In contrast to what is observed in mammals where sexual differentiation essentially proceeds via masculinization of the males, in quail, females are demasculinized by their endogenous ovarian estrogens, an effect that can be blocked by injection of an aromatase inhibitor and mimicked in male embryos by an injection of estradiol. In adulthood, testosterone secreted by the testes is converted into estrogens by the preoptic aromatase. Locally produced estrogens activate male sexual behavior largely through the activation of estrogen receptors resulting in the transcription of a variety of genes, including brain aromatase (genomic effect). Both changes in estrogen production and action are observed within latencies ranging from a few hours to a few days, and are completely reversible. Additionally, brain aromatase activity can be modulated within minutes by calcium-dependent phosphorylations, triggered by variations in glutamatergic neurotransmission. These rapid changes in aromatase activity affect with relatively short latencies (10-15 min) the expression of male sexual behavior in quail and also in mice. Overall, the effects of estrogens on sexual behavior can thus be categorized into three classes: organizational (irreversible genomic action during ontogeny), activational (reversible genomic action during adulthood) and rapid nongenomic effects. Rapid and slower changes in brain aromatase activity match well with the two modes of estrogen action on behavior and provide temporal variations in the estrogens' bioavailability that should be able to support the entire range of established effects for this steroid. [less ▲]

Modulation of steroid action: Importance of steroid binding globulins

Scientific conference (2008)

Modulation of endocrine environment during aggression: It's not all about testosterone

Scientific conference (2008)

Development of a technique to measure 17β-estradiol in discrete brain regions in zebra finch

Poster (2008)

Effect of aggressive interactions on aromatase activity in discrete brain regions in wild male white-crowned sparrows

Poster (2008)

Testosterone (T) is a critical endocrine factor involved in the activation of aggressive behaviors. In many vertebrate species, circulating T levels rapidly increase after aggressive encounters during the ... [more ▼]

Testosterone (T) is a critical endocrine factor involved in the activation of aggressive behaviors. In many vertebrate species, circulating T levels rapidly increase after aggressive encounters during the breeding season. In contrast, we recently showed that circulating T concentrations did not change in white-crowned sparrows in the late breeding season after simulated territorial intrusions. We suggested that changes in local metabolism of T might be more important than changes in systemic T levels. Neural aromatization of T into 17􀀁-estradiol (E2) often mediates the physiological and behavioral actions of T. In vertebrates, aromatase is expressed in several discrete brain regions. We hypothesized that in the late breeding season, brain aromatase is rapidly modulated after aggressive interaction, leading to changes in local concentrations of E2. Wild male white-crowned sparrows were exposed to simulated territorial intrusion with song playback and decoy (STI) or control (CON) for 30 min. STI significantly increased aggressive behaviors. Birds were then caught, rapidly bled and sacrificed. Brains were collected and rapidly frozen on dry ice. We used 0.9 mm diameter punches from 300 μm coronal sections to isolate 13 different brain nuclei. Aromatase activity was analyzed in punches from the left side of the brain, while E2 was analyzed in punches from the right side of the brain. Aromatase activity was quantified by measuring the release of tritiated water during aromatization of [1􀀁-3H]-androstenedione. As expected, aromatase activity was high in the medial preoptic area, ventromedial nucleus of the hypothalamus, hippocampus, bed nucleus of the stria terminalis, nucleus taeniae of the amygdala, and caudomedial nidopallium. Aromatase activity was low in the medial magnocellular nucleus of anterior nidopallium, HVC, Area X, nucleus robustus of the arcopallium, optic lobes, periaqueductal gray and cerebellum. Aromatase activity was not different between the STI and CON groups in any region. There were no significant correlations between aromatase activity and aggressive behaviors or endocrine measures (plasma T, progesterone, corticosterone and corticosteroid binding globulin). These data provide no evidence for rapid modulation of brain aromatase activity following aggressive interactions. It is however possible that aromatase activity is more rapidly modulated (e.g. within 5 min) and these changes were not observed in our 30 min paradigm. We are currently investigating whether local E2 is affected by aggressive interactions. [less ▲]

Novel mechanisms for neuroendocrine regulation of aggression.

in Frontiers in Neuroendocrinology (2008), 29(4), 476-89

In 1849, Berthold demonstrated that testicular secretions are necessary for aggressive behavior in roosters. Since then, research on the neuroendocrinology of aggression has been dominated by the paradigm ... [more ▼]

In 1849, Berthold demonstrated that testicular secretions are necessary for aggressive behavior in roosters. Since then, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives gonadal hormones, primarily testosterone, which modulate relevant neural circuits. While this paradigm has been extremely useful, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when gonads are regressed and circulating testosterone levels are typically low. Studies in birds and mammals suggest that an adrenal androgen precursor-dehydroepiandrosterone (DHEA)-may be important for the expression of aggression when gonadal testosterone synthesis is low. Circulating DHEA can be metabolized into active sex steroids within the brain. Another possibility is that the brain can autonomously synthesize sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels from circulating steroid levels. These alternative neuroendocrine mechanisms to provide sex steroids to specific neural circuits may have evolved to avoid the "costs" of high circulating testosterone during particular seasons. Physiological indicators of season (e.g., melatonin) may allow animals to switch from one neuroendocrine mechanism to another across the year. Such mechanisms may be important for the control of aggression in many vertebrate species, including humans. [less ▲]

Effect of aggressive encounters on plasma progesterone, corticosterone and corticosteroid binding capacity

Poster (2007)

Role of coactivators SRC-1 and CARM1 in estrogen receptor-alpha and beta-dependent cell proliferation in the dentate gyrus of adult female rats

Poster (2007)

Nuclear receptors such as the estrogen receptors (ER) require the presence of coactivator proteins, such as the steroid receptor coactivator (SRC-1) and coactivator-associated arginine methyltransferase ... [more ▼]

Nuclear receptors such as the estrogen receptors (ER) require the presence of coactivator proteins, such as the steroid receptor coactivator (SRC-1) and coactivator-associated arginine methyltransferase (CARM1) to enhance the transcription of target genes. Importantly, in vitro work suggests that ER􀀁 and ER􀀂 differ in the ability to recruit coactivators such as SRC-1. For example, SRC-1 has a strong affinity for ER􀀁 and a weaker affinity for ER􀀂. Interestingly, both ER􀀁 and ER􀀂 are individually involved in estradiol-enhanced cell proliferation in the dentate gyrus of adult female rats. In addition, previous work suggests a role for CARM1 in cell proliferation and for SRC-1 in cell differentiation, therefore the present study aimed to determine whether proliferating cells in the dentate gyrus of the hippocampus co-express the coactivators SRC-1 and CARM1. We also aimed to determine whether ER􀀁 and ER􀀂 agonists would result in altered expression of SRC-1 and CARM1 in new proliferating cells in the dentate gyrus. To investigate this, adult female rats were ovariectomized and treated with either the ER􀀁 agonist Propyl-pyrazole triol (PPT), the ER􀀂 agonist diarylpropionitrile (DPN), estradiol benzoate (EB), or vehicle (CTRL). Rats were then injected with BrdU (200 mg/kg) and sacrificed 24 hours later. Preliminary data suggests that DPN, PPT and EB increase cell proliferation in the dentate gyrus compared to the vehicle-injected group. Interestingly, the number of proliferating cell expressing SRC-1 is similar in all groups, suggesting that neither of the ER agonists nor EB treatment affects the co-expression of BrdU+ cells with SRC-1. However, additional measurements are currently being done to investigate whether CARM-1 is differentially expressed in proliferating cells in the hippocampus following selective ER agonist treatment. [less ▲]

Rapid testosterone-induced apparent diffusion coefficient (ADC) changes in the sexually dimorphic medial preoptic nucleus of male Japanese quail.

Poster (2006)

Testosterone (T) influences the volume and cellular characteristics of a variety of steroid-dependent brain nuclei in many vertebrates. In castrated quail, the volume of the sexually dimorphic (males ... [more ▼]

Testosterone (T) influences the volume and cellular characteristics of a variety of steroid-dependent brain nuclei in many vertebrates. In castrated quail, the volume of the sexually dimorphic (males > females) medial preoptic nucleus (POM), a key area in the control of male sexual behavior, is markedly increased by T but previous studies always assessed this effect after a period of 8-14 days and its specific time-course was unknown. We recently found that following treatment with T, the POM volume increases in a time-dependent fashion: a significant increase was already detected after only one day and the response reached it maximum (volume doubling) after 14 days of treatment. This however raised the question of the cellular mechanism underlying such a rapid brain plasticity (increase in cell size, neuropil volume, dendritic branching, extracellular space?). To research whether a change in extra- vs. intra-cellular space could be responsible for the rapid T-induced increase in POM volume, we repeatedly analyzed by in vivo diffusion-weighted magnetic resonance imaging (DW-MRI) the brain of castrated male quail before as well as after 1, 2, 7 and 14 days of T implantation. MRI was performed on a 7T-system (Bruker) using a multislice diffusion weighted-spin echo sequence. Coronal slices with an image resolution of 100*100*500µm³ were obtained covering the whole telencephalon. Images were accurately coregistered allowing voxel-wise paired comparisons of the ADC data between the different time periods. The ADC significantly increased after one day of T treatment (696±16 vs 758±30 µm²/s, p=0.011, N=5) in POM and this effect apparently persisted during the whole experiment. By contrast, T insensitive regions like the nucleus rotundus (586±170 vs 511±26 µm²/s, p-value=0.24) and nucleus mesencephalicus lateralis, pars dorsalis (934±107 vs 911±64 µm²/s, p=0.68) were not affected after the first day nor later in the experiment. These data indicate that T increases the extracellular water volume in POM specifically, either as a result of cell shrinkage or of an increase in the space between cells, and that changes in the ratio of extra- to intra-cellular water mediate, at least in part, the fast plasticity of the POM volume observed after exposure to T. [less ▲]