RESUMEN
The hypothalamic-pituitary-thyroid axis is governed by hypophysiotropic TRH-synthesizing neurons located in the hypothalamic paraventricular nucleus under control of the negative feedback of thyroid hormones. The mechanisms underlying the ontogeny of this phenomenon are poorly understood. We aimed to determine the onset of thyroid hormone-mediated hypothalamic-negative feedback and studied how local hypothalamic metabolism of thyroid hormones could contribute to this process in developing chicken. In situ hybridization revealed that whereas exogenous T4 did not induce a statistically significant inhibition of TRH expression in the paraventricular nucleus at embryonic day (E)19, T4 treatment was effective at 2 days after hatching (P2). In contrast, TRH expression responded to T3 treatment in both age groups. TSHß mRNA expression in the pituitary responded to T4 in a similar age-dependent manner. Type 2 deiodinase (D2) was expressed from E13 in tanycytes of the mediobasal hypothalamus, and its activity increased between E15 and P2 both in the mediobasal hypothalamus and in tanycyte-lacking hypothalamic regions. Nkx2.1 was coexpressed with D2 in E13 and P2 tanycytes and transcription of the cdio2 gene responded to Nkx2.1 in U87 glioma cells, indicating its potential role in the developmental regulation of D2 activity. The T3-degrading D3 enzyme was also detected in tanycytes, but its level was not markedly changed before and after the period of negative feedback acquisition. These findings suggest that increasing the D2-mediated T3 generation during E18-P2 could provide the sufficient local T3 concentration required for the onset of T3-dependent negative feedback in the developing chicken hypothalamus.
Asunto(s)
Retroalimentación Fisiológica/fisiología , Regulación del Desarrollo de la Expresión Génica/genética , Sistema Hipotálamo-Hipofisario/metabolismo , Yoduro Peroxidasa/metabolismo , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , ARN Mensajero/metabolismo , Glándula Tiroides/metabolismo , Hormona Liberadora de Tirotropina/metabolismo , Tiroxina/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/embriología , Encéfalo/metabolismo , Línea Celular Tumoral , Embrión de Pollo , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Retroalimentación Fisiológica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Sistema Hipotálamo-Hipofisario/embriología , Hipotálamo/efectos de los fármacos , Hipotálamo/embriología , Hipotálamo/metabolismo , Inmunohistoquímica , Hibridación in Situ , Yoduro Peroxidasa/efectos de los fármacos , Neuronas/efectos de los fármacos , Proteínas Nucleares/efectos de los fármacos , Proteínas Nucleares/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/embriología , Hipófisis/efectos de los fármacos , Hipófisis/metabolismo , ARN Mensajero/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor Nuclear Tiroideo 1 , Tirotropina de Subunidad beta/genética , Tiroxina/farmacología , Factores de Transcripción/efectos de los fármacos , Factores de Transcripción/metabolismo , Triyodotironina/efectos de los fármacos , Triyodotironina/metabolismo , Yodotironina Deyodinasa Tipo IIRESUMEN
Sixty male broiler chickens fed a diet supplemented with 130 mg/kg stevioside (S group) or an unsupplemented diet (C group) from day 1 of age onwards. On day 21 of age, ten birds from either the S (SH) or C (CH) group were injected subcutaneously with 100 µg human serum albumin (HSA) and ten others from either S (SP) or C (CP) group injected with 100 µl phosphate-buffered saline (PBS) in the same way. There were no significant effect of supplementation nor interaction with age on average body weights, T(3) and T(4) concentrations of non-injected chickens. After the primary immunization, α(1) -glycoprotein concentrations increased in all treatment groups except the CP group, and were significantly higher in the CH group in relation to the other groups. Fourteen and 18 days after the primary immunization, HSA injected chickens of both dietary treatments had significantly higher anti-HSA immunoglobulin G (IgG) levels than their PBS injected controls. No effect of stevioside supplementation was observed for IgG level. In conclusion, dietary stevioside inclusion can attenuate the pro-inflammatory response after stimulation of the innate immune response in broiler chickens.
Asunto(s)
Pollos/inmunología , Diterpenos de Tipo Kaurano/farmacología , Glucósidos/farmacología , Inmunoglobulina G/sangre , Albúmina Sérica/inmunología , Tiroxina/sangre , Triyodotironina/sangre , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal , Dieta/veterinaria , Suplementos Dietéticos , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/inmunología , Masculino , Albúmina Sérica/clasificación , Edulcorantes/farmacologíaRESUMEN
The ease of in vivo experimental manipulation is one of the main factors that have made the chicken embryo an important animal model in developmental research, including developmental endocrinology. This review focuses on the development of the thyrotropic, corticotropic and somatotropic axes in the chicken, emphasizing the central role of the pituitary gland in these endocrine systems. Functional maturation of the endocrine axes entails the cellular differentiation and acquisition of cell function and responsiveness of the different glands involved, as well as the establishment of top-down and bottom-up anatomical and functional communication between the control levels. Extensive cross-talk between the above-mentioned axes accounts for the marked endocrine changes observed during the last third of embryonic development. In a final paragraph we shortly discuss how genomic resources and new transgenesis techniques can increase the power of the chicken embryo model in developmental endocrinology research.
Asunto(s)
Desarrollo Embrionario , Sistema Endocrino/embriología , Modelos Animales , Animales , Embrión de Pollo , Corticotrofos/fisiología , Retroalimentación Fisiológica , Genómica/métodos , Hipotálamo/embriología , Hipófisis/embriología , Somatotrofos/fisiología , Tirotrofos/fisiologíaRESUMEN
Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corticosterone secretion in chicken. Ghrelin mediates these actions in mammals by binding to the growth hormone secretagogue receptor (GHS-R). In this study, we describe the partial cloning of two chicken GHS-R (cGHS-R) isoforms: cGHS-R1a and cGHS-R1c. cGHS-R1a and cGHS-R1c cDNA show, respectively, 81 and 78% homology with the corresponding parts of the human GHS-R1a cDNA. In contrast to the human GHS-R1b isoform, which is truncated after transmembrane domain 5 (TM-5), the chicken GHS-R1c isoform lacks 16 amino acids in TM-6 suggesting that this isoform is not active in ghrelin signal transduction. The cystein residues, N-linked glycosylation sites and potential phosphorylation sites, found in the human GHS-R1a, were also conserved in both chicken isoforms. RT-PCR analysis demonstrated cGHS-R1a and cGHS-R1c mRNA expression in all tissues tested, except liver and pancreas, with highest levels in the pituitary and the hypothalamus. Intermediate levels of expression were detected, in descending order, in the ovary, telencephalon, heart, adrenal gland, cerebellum, and optic lobes whereas low expression was detected in the brainstem, lung, kidney, proventriculus, duodenum, and colon. Very low expression was found in skin, stomach, and muscle. cGHS-R1c was expressed in lower amounts than cGHS-R1a in all analysed tissues. Administration of 1 microM chicken ghrelin to pituitaries in vitro resulted in a down-regulation of both cGHS-R isoforms within 15 min, whereas after 1h levels returned to control values. Growth hormone and corticosterone down-regulated cGHS-R1a and cGHS-R1c mRNA expression within 60 min of exposure, whereas growth hormone-releasing factor 1-29 (1 microM) only reduced cGHS-R1a mRNA expression after 60min. Thyrotropin-releasing hormone (1 microM) did not alter cGHS-R expression.
Asunto(s)
Pollos/metabolismo , Hipotálamo/metabolismo , Adenohipófisis/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Pollos/genética , Clonación Molecular , ADN Complementario/análisis , Regulación de la Expresión Génica , Datos de Secuencia Molecular , Isoformas de Proteínas/clasificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/análisis , Receptores Acoplados a Proteínas G/clasificación , Receptores de Ghrelina , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Homología de Secuencia de Ácido Nucleico , Distribución TisularRESUMEN
Two rapeseed meals (RM1 and RM2), containing glucosinolates at a concentration of 26 and 40 micromol/g, respectively, were incorporated at increasing levels (10, 20, and 30% for RM1 and 30 and 50% for RM2) in diets of juvenile rainbow trout. Disturbances in the thyroid axis appeared after 14 days of feeding (with a dietary incorporation level of 10%). The dietary supplementation with T(3) or iodine induced an increase in plasma T(3) levels, compared to that in fish fed the RM diets, and reduced the deleterious effect of RM on growth. When trout were reared in seawater, there was also a slight increase in thyroid hormone levels. TSH treatment had no effect on the thyroid hormone plasma levels. The incorporation of 30% of RM1, which induced a lower dietary content of toxic compounds than RM2, led to a rapid decrease of plasma T(4) and T(3) levels, but growth was affected only after 6 months of feeding. During these studies, the deiodinase activities responded in a complex manner to restore plasma and tissue levels of T(3).
Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Brassica rapa/química , Glucosinolatos/farmacología , Oncorhynchus mykiss/fisiología , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Animales , Dieta , Glucosinolatos/administración & dosificación , Yoduro Peroxidasa/metabolismo , Yodo/administración & dosificación , Oncorhynchus mykiss/crecimiento & desarrollo , Agua de Mar , Tirotropina/farmacología , Tiroxina/sangre , Triyodotironina/administración & dosificación , Triyodotironina/sangreRESUMEN
Fasting has severe effects on thyroid metabolism in the chicken: plasma thyroxine (T4) concentrations increase, whereas 3',5,3-triiodothyronine (T3) concentrations decrease. In the present report we studied the effect of fasting at the level of: 1) the pituitary (plasma thyrotropin (TSH) concentrations; the sensitivity of thyrotrophs to corticotropin-releasing hormone (CRH) and TSH-releasing hormone (TRH)); and 2) the hypothalamus (TRH content). A regulatory role of corticosterone is discussed. One day of fasting resulted in a drop in plasma TSH concentrations. Fed and nonfed animals were treated with ovine CRH (oCRH) or TRH. The sensitivity of thyrotrophs to the respective hypothalamic hormones was increased when animals were subjected to a 1-d period of fasting. A 75% (TRH) and 50% (oCRH) increase in plasma TSH was recorded in fasted animals, whereas both secretagogues did not evoke any response in their fed counterparts. The drop in plasma TSH cannot, therefore, be attributed to a loss in sensitivity of thyrotrophs to hypothalamic stimulatory control. In an identical experiment, plasma TSH concentrations decreased, whereas hypothalamic TRH content was higher in fasted animals, suggesting a decreased hypothalamic TRH release toward the pituitary. In both fasting experiments, plasma corticosterone concentrations were increased after 1 d of fasting. Because an i.v. injection of corticosterone-elevated hypothalamic TRH contents and decreased plasma TSH concentrations, a corticosterone-induced TSH decrease during fasting is suggested through an action at the level of the hypothalamus.
Asunto(s)
Pollos/metabolismo , Corticosterona/metabolismo , Hipotálamo/metabolismo , Glándula Tiroides/metabolismo , Tirotropina/metabolismo , Animales , Hormona Liberadora de Corticotropina/metabolismo , Hormona del Crecimiento/sangre , Hipotálamo/química , Masculino , Estado Nutricional/fisiología , Radioinmunoensayo/veterinaria , Tirotropina/análisis , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
The regional distribution of thyrotropin-releasing hormone (TRH) was studied in the chicken brain. The hypothalamus and the brain stem contained the highest concentration of TRH. Lower amounts were present in the telencephalon, the optic lobes and the cerebellum. Within the hypothalamus, TRH was most abundant in the median eminence. Other important TRH sites were the nucleus paraventricularis magnocellularis, nucleus periventricularis hypothalami, nucleus ventromedialis hypothalami, nucleus dorsomedialis hypothalami and nucleus preopticus periventricularis. On the 14th day of embryonic development (E14), TRH was mostly found in the brain stem. Towards hatching, TRH concentrations increased gradually in both the hypothalamic area and the brain stem. TRH concentrations in the telencephalon, optic lobes and cerebellum remained low. Pituitaries from E14 to E16 chickens were characterized by a high TRH concentration, whereas hypophyseal TRH concentrations dropped towards hatching. Our results support the hypothesis that TRH exerts both endocrine and neurocrine actions in the chicken. On the other hand, high pituitary TRH concentrations were present when hypothalamic concentrations were low and vice versa. Therefore, the chicken pituitary may function as an important source of TRH during early in ovo development at least until the moment hypothalamic control develops.
Asunto(s)
Mapeo Encefálico , Encéfalo/metabolismo , Hipófisis/metabolismo , Hormona Liberadora de Tirotropina/metabolismo , Animales , Animales Recién Nacidos , Encéfalo/embriología , Tronco Encefálico/metabolismo , Cerebelo/metabolismo , Embrión de Pollo , Pollos , Hipotálamo/metabolismo , Hipófisis/embriología , Radioinmunoensayo , Sensibilidad y Especificidad , Colículos Superiores/metabolismo , Telencéfalo/metabolismoRESUMEN
Thyrotropin-releasing hormone (TRH) and somatostatin (SRIH) concentrations were determined by RIA during both embryonic development and posthatch growth of the chicken. Both TRH and SRIH were already detectable in hypothalami of 14-day-old embryos (E14). Towards the end of incubation, hypothalamic TRH levels increased progressively, followed by a further increase in newly hatched fowl. SRIH concentrations remained stable from E14 to E17 and doubled between E17 and E18 to a concentration which was observed up to hatching. Plasma GH levels remained low during embryonic development, ending in a steep increase at hatching. Plasma TSH levels on the other hand decreased during the last week of the incubation. During growth, TRH concentrations further increased, whereas SRIH concentrations fell progressively towards those of adult animals. Plasma TSH levels increased threefold up to adulthood; the rise in plasma GH levels during growth was followed by a drop in adults. In conclusion, the present report shows that important changes occur in the hypothalamic TRH and SRIH concentration during both embryonic development and posthatch growth of the chicken. Since TRH and SRIH control GH and TSH release in the chicken, the hypothalamic data are compared with plasma GH and TSH fluctuations.
Asunto(s)
Pollos/metabolismo , Hormona del Crecimiento/sangre , Hipotálamo/química , Somatostatina/análisis , Hormona Liberadora de Tirotropina/análisis , Tirotropina/sangre , Animales , Embrión de Pollo , Pollos/crecimiento & desarrollo , Edad Gestacional , RadioinmunoensayoRESUMEN
Chickens were used as a model to further analyze the efficacy and specificity of L-692,429, a novel nonpeptidyl mimic of growth hormone (GH)-releasing peptide-6 (GHRP-6), which is a specific GH-releasing secretagogue in mammals. Actions at the level of the pituitary and the hypothalamus were studied. Pituitaries isolated from 1-day-old (C1) chicks responded in a dose-dependent manner to L-692,429 (ED50 = 10 nM). Using equimolar concentrations of thyrotropin-releasing hormone (TRH), human GH-releasing hormone (hGHRH1-29), and L-692,429 (10 nM), L-692,429 had 20-25% the in vitro potency of the two endogenous releasing factors. There was an additive effect between hGHRH1-29 (10 nM) and L-692,429 (10 or 100 nM) on GH release from C1 pituitaries but no such additive effect was observed when pituitaries were exposed to both TRH (10 nM) and L-692,429 (100 nM). An acute challenge with 50 microg L-692,429 resulted in increased plasma GH levels within 5 min, which remained elevated for up to 15 min (C1 chickens). This increase in GH was accompanied by a drop in hypothalamic TRH content by 5 min. Hypothalamic somatostatin (SRIH) content did not change. Plasma corticosterone concentrations were increased following L-692,429 treatment, whereas plasma alpha-subunit, T4, and T3 levels were unchanged. To confirm the role of the decreased hypothalamic TRH concentrations in the GH-releasing activity of L-692,429 in the chicken, chickens (C1) were pretreated with normal rabbit serum (NRS) or a TRH antiserum (1/50) 1 h prior to the L-692,429 challenge. Both groups showed an increase in circulating GH but the increase was within 5 min inhibited by the TRH antiserum pretreatment, whereas no differences were noted in plasma corticosterone levels. It is concluded that in the chicken the GH secretagogue L-692,429 has a dual action site: (1) directly at the level of the pituitary and (2) centrally through an increase in hypothalamic TRH release.