RESUMEN
Maternal diets can have dramatic effects on the physiology, metabolism, and behaviour of offspring that persist into adulthood. However, the effects of maternal sucrose consumption on offspring remain unclear. Here, female rats were fed either a sucrose diet with a human-relevant level of sucrose (25% of kcal) or a macronutrient-matched, isocaloric control diet before, during, and after pregnancy. After weaning, all offspring were fed a standard low-sucrose rodent chow. We measured indicators of metabolism (weight, adipose, glucose tolerance, and liver lipids) during development and adulthood (16-24 weeks). We also measured food preference and motivation for sugar rewards in adulthood. Finally, in brain regions regulating these behaviours, we measured steroids and transcripts for steroidogenic enzymes, steroid receptors, and dopamine receptors. In male offspring, maternal sucrose intake decreased body mass and visceral adipose tissue, increased preference for high-sucrose and high-fat diets, increased motivation for sugar rewards, and decreased mRNA levels of Cyp17a1 (an androgenic enzyme) in the nucleus accumbens. In female offspring, maternal sucrose intake increased basal corticosterone levels. These data demonstrate the enduring, diverse, and sex-specific effects of maternal sucrose consumption on offspring phenotype.
Asunto(s)
Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Fenómenos Fisiologicos de la Nutrición Prenatal , Esteroides/metabolismo , Sacarosa/administración & dosificación , Alimentación Animal , Animales , Biomarcadores , Conducta de Elección/efectos de los fármacos , Dieta , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/fisiología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismoRESUMEN
Sucrose consumption is associated with type 2 diabetes, cardiovascular disease, and cognitive deficits. Sucrose intake during pregnancy might have particularly prominent effects on metabolic, endocrine, and neural physiology. It remains unclear how consumption of sucrose affects parous females, especially in brain circuits that mediate food consumption and reward processing. Here, we examine whether a human-relevant level of sucrose before, during, and after pregnancy (17-18 weeks total) influences metabolic and neuroendocrine physiology in female rats. Females were fed either a control diet or a macronutrient-matched, isocaloric sucrose diet (25% of kcal from sucrose). Metabolically, sucrose impairs glucose tolerance, increases liver lipids, and increases a marker of adipose inflammation, but has no effect on body weight or overall visceral adiposity. Sucrose also decreases corticosterone levels in serum but not in the brain. Sucrose increases progesterone levels in serum and in the brain and increases the brain:serum ratio of progesterone in the mesocorticolimbic system and hypothalamus. These data suggest a dysregulation of systemic and local steroid signalling. Moreover, sucrose decreases tyrosine hydroxylase (TH), a catecholamine-synthetic enzyme, in the medial prefrontal cortex. Finally, sucrose consumption alters the expression pattern of FOSB, a marker of phasic dopamine signalling, in the nucleus accumbens. Overall, chronic consumption of sucrose at a human-relevant level alters metabolism, steroid levels, and brain dopamine signalling in a female rat model.
Asunto(s)
Encéfalo/metabolismo , Corticosterona/metabolismo , Sacarosa en la Dieta/farmacología , Dopamina/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Ingestión de Alimentos/fisiología , Femenino , Modelos Animales , Embarazo , RatasRESUMEN
Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11ß-hydroxysteroid dehydrogenase (11ß-HSD) type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11ß-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS) diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11ß-HSD1 or 11ß-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.
Asunto(s)
Dieta Alta en Grasa , Sacarosa en la Dieta/administración & dosificación , Feto/metabolismo , Glucocorticoides/metabolismo , Actividad Motora , Factores Sexuales , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , EmbarazoRESUMEN
Glucocorticoids are important for production of functional lymphocytes and immunity. In altricial neonates, adrenal glands are unresponsive and local glucocorticoid synthesis in lymphoid organs may be necessary to support lymphocyte development. Precocial neonates, in contrast, have fully responsive adrenal glucocorticoid production, and lymphoid glucocorticoid synthesis may not be necessary. Here, we found that in altricial zebra finch hatchlings, lymphoid organs had dramatically elevated endogenous glucocorticoid (and precursor) levels compared to levels in circulating blood. Furthermore, while avian adrenals produce corticosterone, finch lymphoid organs had much higher levels of cortisol, an unexpected glucocorticoid in birds. In contrast, precocial Japanese quail and chicken offspring did not have locally elevated lymphoid glucocorticoid levels, nor did their lymphoid organs contain high proportions of cortisol. These results show that lymphoid glucocorticoids differ in identity, concentration, and possibly source, in hatchlings of three different bird species. Locally-regulated glucocorticoids might have species-specific roles in immune development.
Asunto(s)
Pollos/inmunología , Coturnix/inmunología , Pinzones/inmunología , Hidrocortisona/biosíntesis , Tejido Linfoide/metabolismo , Animales , Animales Recién Nacidos , Pollos/crecimiento & desarrollo , Cromatografía Líquida de Alta Presión , Coturnix/crecimiento & desarrollo , Pinzones/crecimiento & desarrollo , Hidrocortisona/análisis , Inmunoensayo , Tejido Linfoide/inmunología , Especificidad de la EspecieRESUMEN
Multiple components of the immune system are modulated by environmental factors, including exposure to stressors. In particular, chronic stressors can impair development of the immune system, leading to alterations in immune function in adulthood. While these effects have been well established in mammals, less is known about how developmental stress modulates immunity in nonmammalian species. We determined the long-term effects of exposure to early-life stressors on immunity in song sparrows including the swelling response to phytohemagglutinin (PHA) and several measures of constitutive innate immunity. Song sparrows were reared in captivity from 3 d of age and exposed to control conditions, food restriction, or corticosterone (CORT) treatment. Males exposed to food restriction or CORT treatment had less swelling of the wing web in response to PHA than control males; however, neither treatment affected the swelling response to PHA in females. The treatments also had sex-specific effects on constitutive innate immune function. Specifically, CORT-treated males had lower antimicrobial capacity toward a strain of the bacterium E. coli but higher antimicrobial activity toward a strain of the fungus Candida albicans compared to food-restricted or control males. In contrast, neither treatment affected constitutive innate immunity in females. These results suggest that male and female song sparrows may differ in how they allocate resources to development of the immune system when reared in stressful or food-limited conditions.
Asunto(s)
Gorriones/inmunología , Animales , Candida albicans , Corticosterona/farmacología , Escherichia coli , Femenino , Privación de Alimentos , Inmunidad Innata , Masculino , Fitohemaglutininas/inmunología , Factores Sexuales , Gorriones/microbiología , Estrés FisiológicoRESUMEN
Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the complexity of a male's songs, a permanent trait, reflects the size of a song-control region of his brain (HVC), and is correlated with body size and several parameters of immunity, specifically investment in protective proteins. However, the performance of a male's songs, a dynamic trait, is not correlated to immune investment. Complexity of song is correlated with the glucocorticoid stress-response, and in some years response to stress predicts overwinter survival. Experimental manipulations have revealed that stressors in early life impair development of HVC, but that HVC recovers in size by adulthood. These manipulations result in impaired song-complexity and song-learning, but not song-performance. Experimental developmental stressors also affect growth, endocrine physiology, metabolism, and immune-function, often in a sex-specific manner. Combined, these studies suggest that song-complexity provides reliable information about early developmental experience, and about other traits that have critical developmental periods. Birdsong thus provides a multi-faceted sexually selected trait that may be an indicator both of developmental and recent conditions.
Asunto(s)
Gorriones/crecimiento & desarrollo , Gorriones/fisiología , Estrés Fisiológico/fisiología , Vocalización Animal/fisiología , Animales , MasculinoRESUMEN
Variation in early environmental conditions can have long-term effects on physiology and behavior, a process referred to as developmental programming. In particular, exposure to early-life stressors can have long-term effects on regulation of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Although these effects have been well documented in mammals, less is known about how early-life stress affects regulation of these endocrine systems in non-mammalian species. In the current study, we determined the long-term effects of early-life food restriction or corticosterone (CORT) treatment on the HPA axis of song sparrows (Melospiza melodia), including the responses to restraint stress, dexamethasone challenge, and ACTH challenge. In addition, we assessed long-term effects on the HPG axis by measuring sex steroid levels (testosterone in males and 17ß-estradiol in females) before and after a gonadotropin-releasing hormone (GnRH) challenge. Subjects treated with CORT during development had larger increases in CORT in response to ACTH challenge than food-restricted or control subjects. Neither treatment affected the responses of CORT to restraint or dexamethasone. CORT-treated males also had higher initial testosterone levels, but neither treatment affected testosterone levels post-GnRH. Lastly, although GnRH challenge failed to increase circulating estradiol levels in females, females exposed to food restriction or CORT treatment had lower estradiol levels than control females. These results show that exposure to stress can developmentally program the endocrine system of songbirds and illustrate the importance of considering developmental conditions when determining the factors responsible for inter-individual variation in endocrine regulation.
Asunto(s)
Corticosterona/farmacología , Privación de Alimentos , Sistema Hipotálamo-Hipofisario/fisiología , Sistema Hipófiso-Suprarrenal/fisiología , Gorriones/fisiología , Estrés Fisiológico , Estrés Psicológico , Andrógenos/farmacología , Animales , Antiinflamatorios/farmacología , Dexametasona/farmacología , Estradiol/sangre , Femenino , Hormona Liberadora de Gonadotropina/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Testosterona/farmacologíaRESUMEN
A growing body of theoretical and empirical work has addressed the relationship between hypothalamus-pituitary-adrenal (HPA) function and fitness. For example, the corticosterone (CORT)-fitness and CORT-condition hypotheses predict that baseline and/or stress-induced levels of glucocorticoids should relate to fitness, and recent empirical studies have reported relationships between HPA function and fitness-related sexually selected traits. Here we introduce a framework for evaluating whether such relationships reflect functional relationships or developmental correlations. We then address this framework using data from a free-living population of song sparrows (Melospiza melodia). In two independent studies we have found that song complexity (a sexually selected trait) is correlated with stress reactivity: males with more complex vocal repertoires show reduced CORT response to standardized restraint stress. This pattern likely results from the early life environment concurrently affecting development of both song and the HPA axis. Suppression of CORT by dexamethasone was also correlated to measures of body condition and immune function, and females paired to males with higher stress-induced levels of CORT initiated egg-laying later. Finally, stress reactivity predicted overwinter survival in one year, although not in another. Thus, the relationship between HPA axis function and fitness likely varies temporally and by context. Some fitness-related traits may be functionally related to HPA regulation, but many others may be related through developmental correlation.
Asunto(s)
Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Gorriones/metabolismo , Animales , Corticosterona/metabolismo , Femenino , Glucocorticoides/metabolismo , MasculinoRESUMEN
Variation in the prenatal and postnatal environments can have long-term effects on adult phenotype. In humans and other animals, exposure to stressors can lead to long-term changes in physiology. These changes may predispose individuals to disease, especially disorders involving energy metabolism. In addition, by permanently altering metabolic rates and energy requirements, such effects could have important fitness consequences. We determined the effects of early-life food restriction and corticosterone (CORT) treatment on growth and adult body size, body composition (assessed via quantitative magnetic resonance) and metabolic rates in the song sparrow, Melospiza melodia. Nestlings were hand-raised in captivity from 3 days of age. Treatments (ad libitum food, food restriction or CORT treatment) lasted from day 7 to day 60. Both experimental treatments had sex-specific effects on growth. In the nestling period, CORT-treated males weighed more than controls, whereas CORT-treated females weighed less than controls. Food-restricted males weighed the same as controls, whereas food-restricted females weighed less than controls. Both experimental treatments also had sex-specific effects on standard metabolic rate (SMR). Females exposed to food restriction or CORT treatment during development had higher SMRs in adulthood than control females, but neither stressor affected SMR in males. There were no effects of either treatment on adult body size, body composition (lean or fat mass) or peak metabolic rate. Therefore, early-life stress may have sex-specific programming effects on metabolic rates and energy expenditure in song sparrows. In addition, both treatments affected nestling growth in a manner that exaggerated the typical sex difference in nestling mass, which could provide male nestlings with a competitive advantage over their sisters when developing in a poor-quality environment.
Asunto(s)
Metabolismo Basal/fisiología , Composición Corporal , Tamaño Corporal , Privación de Alimentos/fisiología , Caracteres Sexuales , Gorriones/anatomía & histología , Gorriones/crecimiento & desarrollo , Estrés Fisiológico , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Metabolismo Basal/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Tamaño Corporal/efectos de los fármacos , Peso Corporal , Cortisona/sangre , Cortisona/farmacología , Conducta Alimentaria/fisiología , Femenino , Modelos Lineales , Masculino , Comportamiento de Nidificación/efectos de los fármacos , Comportamiento de Nidificación/fisiología , Análisis de Componente Principal , Gorriones/sangre , Gorriones/metabolismo , Estrés Fisiológico/efectos de los fármacos , Vocalización AnimalRESUMEN
Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is a key component of the vertebrate stress response. Prior studies have found that variation in HPA responses were correlated to measures of fitness and physiological condition. In addition, sexually-selected traits have also been found to correlate to measures of condition. The proximate mechanisms responsible for such covariation between sexually selected traits and measures of quality are unclear, but could involve variation in HPA regulation. We investigated whether HPA activity is related to song complexity, body size/condition and leukocyte profiles in wild male song sparrows (Melospiza melodia). We characterized three aspects of HPA activity: 1) response to restraint stress; 2) negative feedback, assessed by the ability of exogenous dexamethasone to suppress corticosterone levels; and 3) adrenal sensitivity to exogenous adrenocorticotropic hormone (ACTH). Birds with lower responses to restraint stress had more complex song and more heterophils and higher heterophil to lymphocyte (H:L) ratios. Birds with more effective negative feedback were larger and had fewer heterophils and lower H:L ratios, suggesting lower levels of physiological stress or infection. We observed no relationship between adrenal sensitivity to exogenous ACTH and any of the factors. These findings illustrate important relationships between HPA activity, song complexity, and morphological and physiological traits. Song complexity may thus provide receivers with information about the ability of the singer to cope with stressors.
Asunto(s)
Comunicación Animal , Sistema Hipotálamo-Hipofisario/fisiología , Gorriones/fisiología , Vocalización Animal/fisiología , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/fisiología , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/farmacología , Animales , Tamaño Corporal , Peso Corporal/fisiología , Hormona Liberadora de Corticotropina/sangre , Dexametasona , Retroalimentación Fisiológica/efectos de los fármacos , Glucocorticoides/sangre , Estado de Salud , Hidrocortisona/sangre , Inmunoensayo , Recuento de Leucocitos , Masculino , Fenotipo , Aptitud Física , Restricción Física , Estrés Psicológico/sangreRESUMEN
Traditionally, sexual differentiation of the brain was thought to be driven by gonadal hormones, particularly testosterone (T). However, recent studies in songbirds suggest that other steroids may also be important. For example, dehydroepiandrosterone (DHEA) can be synthesized by the gonads, adrenal glands, and/or brain and locally metabolized into T and 17ß-estradiol (E(2)). Here, we examined DHEA and E(2) levels in the brain, peripheral tissues, and plasma of wild European starlings (Sturnus vulgaris). In Study 1, samples were collected from males and females at P0 (day of hatch), P6, and P8. In Study 2, samples were collected at P4. At P0, DHEA levels in the diencephalon were higher in males than females. DHEA levels were generally high in the gonads and adrenals, and they were higher in testes than ovaries at P8. Further, E(2) levels were non-detectable in most brain samples, suggesting that DHEA was not metabolized to E(2) or that locally produced E(2) was rapidly inactivated. At P4, DHEA levels in telencephalic regions were lower in males than females. Taken together, these data suggest that sex differences in peripheral DHEA secretion and neural DHEA metabolism at specific ages during development might play a role in sexual differentiation of the songbird brain.
Asunto(s)
Glándulas Suprarrenales/metabolismo , Envejecimiento/metabolismo , Encéfalo/metabolismo , Deshidroepiandrosterona/metabolismo , Estradiol/metabolismo , Gónadas/metabolismo , Diferenciación Sexual , Estorninos/metabolismo , Glándulas Suprarrenales/crecimiento & desarrollo , Factores de Edad , Animales , Encéfalo/crecimiento & desarrollo , Deshidroepiandrosterona/sangre , Estradiol/sangre , Femenino , Gónadas/crecimiento & desarrollo , Masculino , Factores Sexuales , Estorninos/sangre , Estorninos/crecimiento & desarrolloRESUMEN
Predator-induced changes in the glucocorticoid responses of prey have been proposed to mediate indirect predator effects on prey demography. Ambiguities exist, however, as to whether differences in predation threat in the environment at large affect the mean glucocorticoid response in wild birds and mammals, and whether this is likely to affect reproduction. Most studies to date that have examined glucocorticoid responses to environmental variation in predation threat have evaluated just one of the several potential measures of the glucocorticoid response, and this may be the source of many ambiguities. We evaluated multiple measures of the glucocorticoid response [plasma total CORTicosterone, corticosteroid binding globulin (CBG) and free CORT] in male and female song sparrows (Melospiza melodia) sampled at locations differing in predation threat in the environment at large, where we have previously reported reproductive differences suggestive of indirect predator effects. Total CORT varied markedly with predation threat in males but not females whereas the opposite was true for CBG, and both sexes demonstrated the same moderately significant free CORT response. Considering all three indices, a glucocorticoid response to environmental variation in predation threat was evident in both sexes, whereas there were ambiguities considering each index singly. We conclude that collecting multiple physiological measures and conducting multivariate analyses may provide a preferable means of assessing glucocorticoid responses to environmental variation in predation threat, and so help clarify whether such glucocorticoid changes affect reproduction in wild birds and mammals.
Asunto(s)
Corticosterona/sangre , Cadena Alimentaria , Pájaros Cantores/fisiología , Transcortina/análisis , Animales , Colombia Británica , Corticosterona/metabolismo , Ambiente , Femenino , Masculino , Distribución por Sexo , Pájaros Cantores/sangre , Transcortina/metabolismoRESUMEN
The enzyme 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3ß-HSD) catalyzes the conversion of dehydroepiandrosterone to androstenedione, thereby playing a key role in sex steroid synthesis. In peripheral tissues, 3ß-HSD is membrane-bound, is present in both mitochondria and microsomes, and is regulated differentially in these two subcellular compartments. In the brain, 3ß-HSD is present, but its subcellular compartmentalization is unknown. Here, in Study 1, we examined the subcellular localization of 3ß-HSD in the brain of a songbird, the zebra finch. In Study 2, in males and females, we determined whether 3ß-HSD activity in different subcellular compartments is rapidly regulated by in vitro treatment with estradiol (E(2) ), which has many rapid effects on the brain. Brain 3ß-HSD was enriched primarily in microsomes and secondarily in mitochondria and synaptosomes. In both males and females, E(2) treatment rapidly (within 5 min) inhibited 3ß-HSD activity in both mitochondria/synaptosomes and microsomes, with greater inhibition in microsomes. We also assessed the activity of 5ß-reductase, which acts on androstenedione. E(2) rapidly inhibited 5ß-reductase activity in microsomes only. This is the first study to examine the subcellular localization of 3ß-HSD in the brain, and the data demonstrate the importance of subcellular localization for the regulation of steroidogenic enzymes in the brain.
Asunto(s)
3-Hidroxiesteroide Deshidrogenasas/metabolismo , Encéfalo/enzimología , Estradiol/farmacología , Pinzones/fisiología , Fracciones Subcelulares/metabolismo , Animales , Encéfalo/efectos de los fármacos , Química Encefálica/fisiología , Deshidroepiandrosterona/metabolismo , Femenino , Masculino , Microsomas/enzimología , Microsomas/metabolismo , Mitocondrias/enzimología , Mitocondrias/metabolismo , Oxidorreductasas/metabolismo , Caracteres Sexuales , Fracciones Subcelulares/efectos de los fármacos , Sinaptosomas/enzimología , Sinaptosomas/metabolismoRESUMEN
Early influences such as maternal stress affect the developmental outcome of the offspring. We created an animal model of postpartum depression/stress based on giving high levels of corticosterone (CORT) to the rat dam, which resulted in behavioral and neural changes in the offspring. This study investigated whether highly elevated levels of maternal CORT during pregnancy or the postpartum result in higher levels of CORT in the stomach milk, serum, and brain of offspring. Dams received daily injections of CORT (40 mg/kg) or oil (control) either during pregnancy (gestational days 10-20) or the postpartum (Days 2-21). Pups that were exposed to high gestational maternal CORT had higher CORT levels in serum, but not in stomach milk or brain, on postnatal day (PND) 1. However, on PND7, pups that were exposed to high postpartum maternal CORT had higher CORT levels in stomach milk and brain, but not in serum. Conversely on PND18, pups that were exposed to high postpartum maternal CORT had higher CORT levels in serum, but not in brain (prefrontal cortex, hypothalamus, or hippocampus). Moreover, 24 h after weaning, there were no significant differences in serum CORT levels between the groups. Thus, CORT given to the dam during pregnancy or the postpartum results in elevated levels of CORT in the offspring, but in an age- and tissue-dependent manner. Developmental exposure to high CORT could reprogram the HPA axis and contribute to the behavioral and neural changes seen in adult offspring.
Asunto(s)
Encéfalo/metabolismo , Corticosterona/sangre , Depresión Posparto/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Estrés Psicológico/metabolismo , Animales , Encéfalo/crecimiento & desarrollo , Corticosterona/metabolismo , Corticosterona/farmacología , Modelos Animales de Enfermedad , Femenino , Sistema Hipotálamo-Hipofisario/crecimiento & desarrollo , Lactancia/metabolismo , Masculino , Intercambio Materno-Fetal/efectos de los fármacos , Intercambio Materno-Fetal/fisiología , Leche/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
Glucocorticoids (GCs) affect the development of both the immune and nervous systems. To do so, GCs bind to intracellular receptors, mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). In addition, GCs bind to membrane-associated corticosteroid receptors (mCR). Two well-known GCs are corticosterone and cortisol. Whereas corticosterone is the primary GC in zebra finch plasma, cortisol is the primary GC in zebra finch lymphoid organs and is also present in the brain and plasma during development. Here, we characterized binding sites for corticosterone and cortisol in plasma, liver, lymphoid organs, and brain of developing zebra finches. In tissues, we examined both intracellular and membrane-associated binding sites. For intracellular receptors, there were MR-like sites and GR-like sites, which differentially bound corticosterone and cortisol in a tissue-specific manner. For mCR, we found little evidence for membrane-associated receptors in immune organs, but this could be due to the small size of immune organs. Interestingly, cortisol, but not corticosterone, showed a low amount of specific binding to bursa of Fabricius membranes. For neural membranes, corticosterone bound to one site with low affinity but a relatively high B(max), and in contrast, cortisol bound to one site with high affinity but a lower B(max). Our results indicate that intracellular and membrane-associated receptors differentially bind corticosterone and cortisol suggesting that corticosterone and cortisol might have different roles in immune and nervous system development.
Asunto(s)
Química Encefálica/fisiología , Encéfalo/crecimiento & desarrollo , Pinzones/fisiología , Sistema Inmunológico/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Esteroides/metabolismo , Animales , Bolsa de Fabricio/metabolismo , Corticosterona/metabolismo , Citosol/metabolismo , Femenino , Globulinas/metabolismo , Hidrocortisona/metabolismo , Hígado/metabolismo , Sistema Linfático/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Membranas/metabolismo , Músculo Esquelético/metabolismo , Ensayo de Unión Radioligante , Receptores de Glucocorticoides/sangre , Receptores de Esteroides/sangre , Timo/metabolismoRESUMEN
The brain and other organs locally synthesize steroids. Local synthesis is suggested when steroid levels are higher in tissue than in the circulation. However, measurement of both circulating and tissue steroid levels are subject to methodological considerations. For example, plasma samples are commonly used to estimate circulating steroid levels in whole blood, but steroid levels in plasma and whole blood could differ. In addition, tissue steroid measurements might be affected by blood contamination, which can be addressed experimentally by using saline perfusion to remove blood. In Study 1, we measured corticosterone and testosterone (T) levels in zebra finch (Taeniopygia guttata) plasma, whole blood, and red blood cells (RBC). We also compared corticosterone in plasma, whole blood, and RBC at baseline and after 60 min restraint stress. In Study 2, we quantified corticosterone, dehydroepiandrosterone (DHEA), T, and 17ß-estradiol (E2) levels in the brains of sham-perfused or saline-perfused subjects. In Study 1, corticosterone and T concentrations were highest in plasma, significantly lower in whole blood, and lowest in RBC. In Study 2, saline perfusion unexpectedly increased corticosterone levels in the rostral telencephalon but not other regions. In contrast, saline perfusion decreased DHEA levels in caudal telencephalon and diencephalon. Saline perfusion also increased E2 levels in caudal telencephalon. In summary, when comparing local and systemic steroid levels, the inclusion of whole blood samples should prove useful. Moreover, blood contamination has little or no effect on measurement of brain steroid levels, suggesting that saline perfusion is not necessary prior to brain collection. Indeed, saline perfusion itself may elevate and lower steroid concentrations in a rapid, region-specific manner.
Asunto(s)
Encéfalo/patología , Corticosterona/sangre , Cloruro de Sodio/metabolismo , Esteroides/metabolismo , Testosterona/sangre , Animales , Encéfalo/metabolismo , Deshidroepiandrosterona/sangre , Eritrocitos/metabolismo , Estrógenos/sangre , Pinzones , Isquemia , Masculino , Modelos Biológicos , Perfusión , Radioinmunoensayo , Distribución TisularRESUMEN
The gonadal hormone testosterone (T) regulates aggression across a wide range of vertebrate species. Recent evidence suggests that the adrenal prohormone dehydroepiandrosterone (DHEA) may also play an important role in regulating aggression. DHEA can be converted into active sex steroids, such as T and estradiol (E(2)), within the brain. Previous studies show that circulating DHEA levels display diurnal rhythms and that melatonin increases adrenal DHEA secretion in vitro. Here we examined serum DHEA and T levels in long-day housed Siberian hamsters (Phodopus sungorus), a nocturnal species in which melatonin treatment increases aggression. In Experiment 1, serum DHEA and T levels were measured in adult male hamsters during the day (1200 h, noon) and night (2400 h, midnight). In Experiment 2, aggression was elicited using 5-min resident-intruder trials during the day (1800 h) and night (2000 h) (lights-off at 2000 h). Serum DHEA and T levels were measured 24 h before and immediately after aggressive encounters. In Experiment 1, there was no significant difference in serum DHEA or T levels between noon and midnight, although DHEA levels showed a trend to be lower at midnight. In Experiment 2, territorial aggression was greater during the night than the day. Moreover, at night, aggressive interactions rapidly decreased serum DHEA levels but increased serum T levels. In contrast, aggressive interactions during the day did not affect serum DHEA or T levels. These data suggest that nocturnal aggressive encounters rapidly increase conversion of DHEA to T and that melatonin may play a permissive role in this process.
Asunto(s)
Agresión/fisiología , Deshidroepiandrosterona/sangre , Phodopus/fisiología , Fotoperiodo , Testosterona/sangre , Animales , Cricetinae , Masculino , Territorialidad , Factores de TiempoRESUMEN
Glucocorticoids (GCs) are produced in the adrenal glands and also in extra-adrenal sites, including immune organs and brain. Here, we examined regulation of systemic GC levels in plasma and local GC levels in immune organs and brain during development. We conducted two studies and examined a total of 462 samples from 70 subjects. In study 1, we determined corticosterone and cortisol levels in the plasma, immune organs, and brain of wild European starlings on posthatch day 0 (P0) and P10 (at baseline and after 45 min of restraint). Baseline corticosterone and cortisol levels were low in the immune organs and brain at P0 and P10, providing little evidence for local GC synthesis in starlings. At P0, restraint had no significant effects on corticosterone or cortisol levels in the plasma or tissues; however, there was a trend for restraint to increase both corticosterone and cortisol in the immune organs. At P10, restraint increased corticosterone levels in the plasma and all tissues, but restraint increased cortisol levels in the plasma, thymus, and diencephalon only. In study 2, we directly compared GC levels in European starlings and zebra finches at P4. In zebra finches but not starlings, cortisol levels were higher in the immune organs than in plasma. This difference in immune GC levels might be due to evolutionary lineage, life history strategy, or experiential factors, such as parasite exposure. This is the first study to measure immune GC levels in wild animals and one of the first studies to measure local GC levels after restraint stress.
Asunto(s)
Encéfalo/metabolismo , Corticosterona/sangre , Pinzones/metabolismo , Hidrocortisona/sangre , Tejido Linfoide/metabolismo , Restricción Física , Estorninos/metabolismo , Estrés Psicológico/sangre , Factores de Edad , Animales , Encéfalo/crecimiento & desarrollo , Bolsa de Fabricio/metabolismo , Femenino , Pinzones/crecimiento & desarrollo , Tejido Linfoide/crecimiento & desarrollo , Masculino , Especificidad de la Especie , Bazo/metabolismo , Estorninos/crecimiento & desarrollo , Estrés Psicológico/etiología , Timo/metabolismoRESUMEN
Traditionally, the production and regulation of steroid hormones has been viewed as a multi-organ process involving the hypothalamic-pituitary-gonadal (HPG) axis for sex steroids and the hypothalamic-pituitary-adrenal (HPA) axis for glucocorticoids. However, active steroids can also be synthesized locally in target tissues, either from circulating inactive precursors or de novo from cholesterol. Here, we review recent work demonstrating local steroid synthesis, with an emphasis on steroids synthesized in the brain (neurosteroids) and steroids synthesized in the immune system (immunosteroids). Furthermore, recent evidence suggests that other components of the HPG axis (luteinizing hormone and gonadotropin-releasing hormone) and HPA axis (adrenocorticotropic hormone and corticotropin-releasing hormone) are expressed locally in target tissues, potentially providing a mechanism for local regulation of neurosteroid and immunosteroid synthesis. The balance between systemic and local steroid signals depends critically on life history stage, species adaptations, and the costs of systemic signals. During particular life history stages, there can be a shift from systemic to local steroid signals. We propose that the shift to local synthesis and regulation of steroids within target tissues represents a "Balkanization" of the endocrine system, whereby individual tissues and organs may become capable of autonomously synthesizing and modulating local steroid signals, perhaps independently of the HPG and HPA axes.
Asunto(s)
Encéfalo/metabolismo , Sistema Inmunológico/metabolismo , Esteroides/biosíntesis , Animales , Aves/fisiología , Hormonas Gonadales/biosíntesisRESUMEN
Sexual differentiation of the brain has traditionally been thought to be driven by gonadal hormones, particularly testosterone (T). Recent studies in songbirds and other species have indicated that non-gonadal sex steroids may also be important. For example, dehydroepiandrosterone (DHEA)--a sex steroid precursor that can be synthesized in the adrenal glands and/or brain--can be converted into active sex steroids, such as 17beta-estradiol (E(2)), within the brain. Here, we examine plasma DHEA and E(2) levels in wild developing European starlings (Sturnus vulgaris), from hatch (P0) to fledging (P20). Blood samples were collected from either the brachial vein (n=143) or the jugular vein (n=129). In songbirds, jugular plasma is enriched with neurally-synthesized steroids and, therefore, jugular plasma is an indirect measure of the neural steroidal milieu. Interestingly, brachial DHEA levels were higher in males than females at P4. In contrast, jugular DHEA levels were higher in females than males at P0 and P10. Brachial E(2) levels were higher in males than females at P6. Surprisingly, jugular E(2) levels were not high and showed no sex differences. Also, we calculated the difference between brachial and jugular steroid levels. At several ages, jugular steroid levels were lower than brachial levels, particularly in males, suggesting greater neural metabolism of circulating DHEA and E(2) in males than females. At a few ages, jugular steroid levels were higher than brachial levels, suggesting neural secretion of DHEA or E(2) into the general circulation. Taken together, these data suggest that DHEA may play a role in brain sexual differentiation in songbirds.