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1.
J Endocrinol Invest ; 44(4): 661-677, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32767280

RESUMEN

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) or autoimmune polyglandular syndrome type 1 (APS-1) is a rare autosomal recessive genetic disease due to mutations in the AIRE (AutoImmune REgulator) gene. The clinical diagnosis is classically based on the presence of at least two of the three main components: chronic mucocutaneous candidiasis, hypoparathyroidism and primary adrenal insufficiency. Patients often suffer from other endocrine or non-endocrine autoimmune conditions throughout life. APECED etiopathogenesis is mediated by T lymphocytes. Autoantibodies against proteins of the affected organs are found in the serum of APECED patients as well as neutralizing antibodies against cytokines. We report here the clinical and genetic characteristics of 45 Indian APECED patients in comparison to Finnish, Sardinian, Turkish and North/South American cohorts from their published results. We also report a new case of APECED of Indian origin, a 2-year old child suffering from chronic mucocutaneous candidiasis since the age of 8 months, with confirmatory AIRE homozygous mutation c.274C > T (p.R92W). CONCLUSION: With the inherent limitations of a retrospective study, analysis of Indian APECED patients suggested that compared to classic criteria, application of Ferre/Lionakis criteria validated in North/South American patients could help in earlier diagnosis in 3 of 8 (37.5%) patients for whom adequate information for evaluation was available.


Asunto(s)
Enfermedad de Addison , Candidiasis Mucocutánea Crónica , Hipoparatiroidismo , Poliendocrinopatías Autoinmunes , Factores de Transcripción/genética , Enfermedad de Addison/diagnóstico , Enfermedad de Addison/etiología , Candidiasis Mucocutánea Crónica/diagnóstico , Candidiasis Mucocutánea Crónica/etiología , Preescolar , Diagnóstico Diferencial , Diagnóstico Precoz , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Humanos , Hipoparatiroidismo/diagnóstico , Hipoparatiroidismo/etiología , India/epidemiología , Masculino , Mutación , Poliendocrinopatías Autoinmunes/diagnóstico , Poliendocrinopatías Autoinmunes/epidemiología , Poliendocrinopatías Autoinmunes/genética , Poliendocrinopatías Autoinmunes/fisiopatología , Proteína AIRE
2.
Ann Dermatol Venereol ; 147(1): 41-45, 2020 Jan.
Artículo en Francés | MEDLINE | ID: mdl-31677808

RESUMEN

INTRODUCTION: Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to chronic or recurrent infections with yeasts of the genus Candida affecting the skin, nails and mucous membranes. We describe a Moroccan patient presenting CMC with heterozygous STAT1 gain-of-function (GOF) mutation. PATIENTS AND METHODS: A 5-year-old boy with no consanguinity presented recurrent episodes of oral thrush, chronic nail candidiasis and herpetic gingivostomatitis from the age of 8 months. He also had mycobacterial adenitis secondary to BCG vaccination and atypical rosacea. Genetic analysis revealed GOF mutation of the STAT1 gene. DISCUSSION: CMC was diagnosed in our patient despite poor clinical features. Sequencing of the genome revealed STAT1GOF mutation. This mutation affects production of IL-17, an important cytokine in mucocutaneous defense against Candida. The association with mycobacterial adenitis is rare and continues to be poorly understood. The presence of atypical rosacea in this setting is suggestive of this entity. Antifungal therapy and prevention of complications are necessary to reduce the morbidity and mortality associated with this condition. CONCLUSION: CMC due to STAT1GOF mutation is characterized by a broad clinical spectrum and should be considered in all cases of chronic or recurrent fungal infection, whether or not associated with other infections.


Asunto(s)
Candidiasis Mucocutánea Crónica/genética , Mutación con Ganancia de Función , Factor de Transcripción STAT1/genética , Adyuvantes Inmunológicos/efectos adversos , Vacuna BCG/efectos adversos , Candidiasis Mucocutánea Crónica/complicaciones , Candidiasis Bucal/complicaciones , Chalazión/complicaciones , Preescolar , Enfermedad Crónica , Enfermedades de las Encías/virología , Humanos , Linfadenitis/microbiología , Masculino , Infecciones por Mycobacterium/complicaciones , Onicomicosis/complicaciones , Estomatitis Herpética/complicaciones
3.
Org Biomol Chem ; 17(38): 8716-8720, 2019 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-31538639

RESUMEN

Nicotinamide adenine dinucleotide, NAD+, is an essential cofactor and substrate for many cellular enzymes. Its sustained intracellular levels have been linked to improved physiological end points in a range of metabolic diseases. Biosynthetic precursors to NAD+ include nicotinic acid, nicotinamide, the ribosylated parents and the phosphorylated form of the ribosylated parents. By combining solvent-assisted mechanochemistry and sealed reaction conditions, access to the ribosylated NAD+ precursors and to the isotopologues of NAD+ precursors was achieved in high yields and levels of purity. The latter is critical as it offers means to better trace biosynthetic pathways to NAD+, investigate the multifaceted roles of the intracellular NAD+ pools, and better exploit NAD+ biology.


Asunto(s)
NAD/síntesis química , Estructura Molecular , NAD/química
5.
R Soc Open Sci ; 8(3): 201703, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-34035937

RESUMEN

Liquid-assisted mechanochemistry as a versatile approach for the coupling of a nucleoside phosphoramidite with a 5'-OH partially protected nucleoside has been investigated. Noted advantages over reported methods were a simplified reaction protocol, a drastic reduction in the use of toxic solvents, the facilitation of mechanochemical reactions through the improved mixing of solid reagents, and low hydrolytic product formation.

6.
Reprod Domest Anim ; 45 Suppl 3: 42-9, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24417198

RESUMEN

Goats and sheep generally express seasonal variations in their sexual behaviour, spermatogenic activity (from moderate decrease to very low sperm production), gamete quality (variations in fertilization rates and embryo survival), ovulation frequency (presence or absence of ovulation), and ovulation rate (number of eggs shed per ovulation period). This induces seasonal availability of derived, fresh animal products (meat, milk and cheese) because of a more or less marked seasonal distribution of births. A complex combination of an endogenous circannual rhythm driven and synchronized by light and melatonin, which controls the pulsatile activity of GnRH neurons in the preoptic-mediobasal hypothalamus, is responsible for these changes. Dramatic and long-term neuroendocrine changes, involving different neuromediator systems and neuronal plasticity, have been shown to play a role in these processes. A strong variability between breeds exists in both species regarding the dates of onset and end of the breeding season, with a gradient of seasonality from southern to northern latitudes. Within a breed, seasonal traits are heritable; thus, genetic selection could be one way to decrease seasonality in sheep and goats in the future.


Asunto(s)
Cabras/fisiología , Sistemas Neurosecretores/fisiología , Reproducción , Estaciones del Año , Ovinos/fisiología , Animales , Cruzamiento , Femenino , Variación Genética , Hormona Liberadora de Gonadotropina , Lactancia , Masculino , Melatonina/metabolismo , Ovario/fisiología , Fotoperiodo , Embarazo , Reproducción/genética , Especificidad de la Especie , Espermatogénesis
7.
Int J Androl ; 32(2): 156-65, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17971162

RESUMEN

Contrary to the traditional view, recent studies suggest that diabetes mellitus has an adverse influence on male reproductive function. Our aim was to determine the effect of diabetes on the testicular environment by identifying and then assessing perturbations in small molecule metabolites. Testes were obtained from control and streptozotocin-induced diabetic C57BL/6 mice, 2, 4 and 8 weeks post-treatment. Diabetic status was confirmed by glycated haemoglobin, non-fasting blood glucose, physiological condition and body weight. A novel extraction procedure was utilized to obtain protein free, low-molecular weight, water soluble extracts which were then assessed using (1)H nuclear magnetic resonance spectroscopy. Principal component analysis of the derived profiles was used to classify any variations, and specific metabolites were identified based on their spectral pattern. Characteristic metabolite profiles were identified for control and type 1 diabetic animals with the most distinctive being from mice with the largest physical deterioration and loss of body weight. Eight streptozotocin-treated animals did not develop diabetes and displayed profiles similar to controls. Diabetic mice had decreases in creatine, choline and carnitine and increases in lactate, alanine and myo-inositol. Betaine levels were found to be increased in the majority of diabetic mice but decreased in a few animals with severe loss of body weight and physical condition. The association between perturbations in a number of small molecule metabolites known to be influential in sperm function, with diabetic status and physiological condition, adds further impetus to the proposal that diabetes influences important spermatogenic pathways and mechanisms in a subtle and previously unrecognized manner.


Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Testículo/metabolismo , Animales , Betaína/metabolismo , Carnitina/metabolismo , Colina/metabolismo , Creatina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/fisiopatología , Fertilidad , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Análisis de Componente Principal , Espermatogénesis
8.
J Enzyme Inhib Med Chem ; 24(6): 1291-318, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19912064

RESUMEN

In drug discovery, different methods exist to create new inhibitors possessing satisfactory biological activity. The multisubstrate adduct inhibitor (MAI) approach is one of these methods, which consists of a covalent combination between analogs of the substrate and the cofactor or of the multiple substrates used by the target enzyme. Adopted as the first line of investigation for many enzymes, this method has brought insights into the enzymatic mechanism, structure, and inhibitory requirements. In this review, the MAI approach, applied to different classes of enzyme, is reported from the point of view of biological activity.


Asunto(s)
Biología/métodos , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Enzimas/farmacología , Sitios de Unión , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Enzimas/química , Enzimas/clasificación , Enzimas/metabolismo , Concentración 50 Inhibidora , Cinética , Relación Estructura-Actividad , Especificidad por Sustrato
9.
Neurosci Lett ; 713: 134520, 2019 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-31562884

RESUMEN

New neurons are continuously added in the dentate gyrus of the hippocampus, the olfactory bulb and the hypothalamus of mammalian brain. In sheep, while the control of adult neurogenesis by the social environment or the photoperiod has been the subject of several studies, its regulation by intrinsic factors, like hormones or neurotransmitters is less documented. We addressed this question by investigating the effects of central oxytocin administration on hippocampal, olfactory and hypothalamic neurogenesis. Endogenous markers, Ki67, Sox2 and DCX were used to assess cell proliferation, progenitor cells density and cell survival respectively in non-gestant ewes receiving a steroid treatment followed by intracerebroventricular injections of either oxytocin or saline. The results showed that oxytocin treatment significantly decreases the density of neuroblasts in the olfactory bulb, increases the density of neuroblasts in the ventromedian nucleus of the hypothalamus while no change is observed in both ventral and dorsal dentate gyrus. In addition, no change in the density of progenitor cells is found in the three neurogenic niches. These findings show for the first time that in females, oxytocin can regulate adult neurogenesis by acting on neuroblasts but not on progenitor cells and that this regulation is region specific.


Asunto(s)
Giro Dentado/fisiología , Células-Madre Neurales/fisiología , Neurogénesis/efectos de los fármacos , Bulbo Olfatorio/fisiología , Oxitocina/farmacología , Núcleo Hipotalámico Ventromedial/fisiología , Animales , Recuento de Células/estadística & datos numéricos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Femenino , Infusiones Intraventriculares , Neurogénesis/fisiología , Ovinos
10.
Reprod Domest Anim ; 43 Suppl 2: 40-7, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18638103

RESUMEN

Farm mammals generally express seasonal variations in their production traits, thus inducing changing availability of fresh derived animal products (meat, milk and cheese) or performances (horses). This is due to a more or less marked seasonal birth distribution in sheep and goats, in horses but not cattle. Birth peak occurs at the end of winter-early spring, the most favourable period for the progeny to survive. Most species show seasonal variations in their ovulation frequency (presence or absence of ovulation), spermatogenic activity (from moderate decrease to complete absence of sperm production), gamete quality (variations in fertilization rates and embryo survival), and also sexual behaviour. The intimate mechanism involved is a complex combination of endogenous circannual rhythm driven and synchronized by light and melatonin. Profound and long-term neuroendocrine changes involving different neuromediator systems were described to play a role in these processes. In most species artificial photoperiodic treatments consisting of extra-light during natural short days (in sheep and goats and mares) or melatonin during long days (in sheep and goats) are extensively used to either adjust the breeding season to animal producer needs and/or to completely overcome seasonal variations of sperm production in artificial insemination centres. Pure light treatments (without melatonin), especially when applied in open barns, could be considered as non-invasive ones which fully respect animal welfare. Genetic selection could be one of the future ways to decrease seasonality in sheep and goats.


Asunto(s)
Estro/fisiología , Melatonina/fisiología , Reproducción/fisiología , Conducta Sexual Animal/fisiología , Espermatogénesis/fisiología , Luz Solar , Animales , Bovinos/fisiología , Femenino , Cabras/fisiología , Caballos/fisiología , Masculino , Periodicidad , Estaciones del Año , Ovinos/fisiología , Especificidad de la Especie
11.
Beilstein J Org Chem ; 2: 14, 2006 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-16859550

RESUMEN

Standard reaction conditions for the desilylation of acetylated furanoside (riboside, arabinoside and xyloside) derivatives facilitate acyl migration. Conditions which favour intramolecular and intermolecular mechanisms have been identified with intermolecular transesterifications taking place under mild basic conditions when intramolecular orthoester formations are disfavoured. In acetyl ribosides, acyl migration could be prevented when desilylation was catalysed by cerium ammonium nitrate.

12.
J Mol Biol ; 307(1): 107-17, 2001 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-11243807

RESUMEN

Dystrobrevins are protein components of the dystrophin complex, whose disruption leads to Duchenne muscular dystrophy and related diseases. The Caenorhabditis elegans dystrobrevin gene (dyb-1) encodes a protein 38 % identical with its mammalian counterparts. The C. elegans dystrobrevin is expressed in muscles and neurons. We characterised C. elegans dyb-1 mutants and showed that: (1) their behavioural phenotype resembles that of dystrophin (dys-1) mutants; (2) the phenotype of dyb-1 dys-1 double mutants is not different from the single ones; (3) dyb-1 mutants are more sensitive than wild-type animals to reductions of acetylcholinesterase levels and have an increased response to acetylcholine; (4) dyb-1 mutations alone do not lead to muscle degeneration, but synergistically produce a progressive myopathy when combined with a mild MyoD/hlh-1 mutation. All together, these findings further substantiate the role of dystrobrevins in cholinergic transmission and as functional partners of dystrophin.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/genética , Proteínas del Helminto/genética , Proteínas del Tejido Nervioso , Neuropéptidos/genética , Acetilcolina/fisiología , Acetilcolinesterasa/metabolismo , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/fisiología , Clonación Molecular , Modelos Animales de Enfermedad , Electrofisiología , Fluoresceínas , Expresión Génica , Proteínas del Helminto/fisiología , Datos de Secuencia Molecular , Proteínas Musculares , Enfermedades Musculares/genética , Enfermedades Musculares/fisiopatología , Mutación , Factores Reguladores Miogénicos , Neuropéptidos/fisiología , Proteínas Nucleares , Ouabaína/análogos & derivados , Fenotipo , Homología de Secuencia de Aminoácido , Factores de Transcripción/genética , Factores de Transcripción/fisiología
13.
J Biol Rhythms ; 16(4): 336-47, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11506379

RESUMEN

In mammals, photoperiodic information is transformed into a melatonin secretory rhythm in the pineal gland (high levels at night, low levels during the day). Melatonin exerts its effects in discrete hypothalamic areas, most likely through MT1 melatonin receptors. Whether melatonin is brought to the hypothalamus from the cerebrospinal fluid or the blood is still unclear. The final action of this indoleamine at the level of the central nervous system is a modulation of GnRH secretion but it does not act directly on GnRH neurones; rather, its action involves a complex neural circuit of interneurones that includes at least dopaminergic, serotoninergic and aminoacidergic neurones. In addition, this network appears to undergo morphological changes between seasons.


Asunto(s)
Fenómenos Cronobiológicos/fisiología , Mamíferos/fisiología , Melatonina/fisiología , Fotoperiodo , Glándula Pineal/fisiología , Animales , Hormona Liberadora de Gonadotropina/fisiología , Humanos , Estaciones del Año
14.
Neuropharmacology ; 33(6): 737-43, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7936111

RESUMEN

In rat hippocampal slices, BC 264 (0.1-1 microM), a highly potent and selective CCK-B agonist, was found to increase basal release of endogenous glutamate and aspartate but not that of GABA. The natural peptide cholecystokinin octapeptide (CCK8) at 1 microM, induced the same effect. The selective CCK-B receptor antagonist, L-365,260, completely reversed these responses, confirming that they are related to CCK-B receptor activation. In the absence of extracellular Ca2+, the increase in excitatory amino acid release was completely abolished. In contrast to the basal release, the potassium evoked release of aspartate and glutamate was not modified by BC 264.


Asunto(s)
Ácido Aspártico/metabolismo , Colecistoquinina/análogos & derivados , Ácido Glutámico/metabolismo , Hipocampo/metabolismo , Fragmentos de Péptidos/farmacología , Compuestos de Fenilurea , Receptores de Colecistoquinina/agonistas , Sincalida/farmacología , Secuencia de Aminoácidos , Animales , Benzodiazepinonas/farmacología , Calcio/fisiología , Colecistoquinina/farmacología , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Masculino , Datos de Secuencia Molecular , Cloruro de Potasio/farmacología , Ratas , Ratas Sprague-Dawley
15.
Thromb Haemost ; 56(3): 250-5, 1986 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-2436328

RESUMEN

A new solid phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of human Factor VII antigen (F VII Ag), using a monospecific rabbit anti-F VII antiserum. Anti-F VII F(ab')2 fragments were adsorbed to polystyrene plates. The binding of serial dilutions of control or test plasma, containing F VII, was detected by incubation with peroxidase-labeled anti- FV II IgG followed by the addition of hydrogen peroxyde and O-phenylenediamine. This ELISA is specific, sensitive (detection limit: 0.05%) and accurate (coefficient of variation: 1.5-4% for within- and 1.6-9% for between-assays). F VII coagulant activity (F VII C) and F VII C) and F VII Ag were determined in large populations of controls and patients. In normal plasma (n = 38), F VII Ag ranged from 83 to 117% and the correlation coefficient between F VII Ag and F VII C was 0.94. In patients with severe (F VII C inf. 1%) congenital F VII deficiency (n = 5), F VII Ag was undetectable in two cases (inf. 0.05%) and markedly reduced (0.35 to 5.6%) in the three other cases. In patients with liver cirrhosis (n = 15), F VII Ag ranged from 21% to 59% and was in good correlation with F VII C (r = 0.84). In dicoumarol treated patients (n = 15), the levels of F VII Ag ranged from 51% to 79% and a poor correlation (r = 0.52) with F VII C was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Factor VII/análisis , Especificidad de Anticuerpos , Antígenos/análisis , Dicumarol/uso terapéutico , Coagulación Intravascular Diseminada/sangre , Epítopos/análisis , Factor VII/inmunología , Factor VII/metabolismo , Deficiencia del Factor VII/sangre , Humanos , Cirrosis Hepática/sangre , Trombosis/sangre
16.
Peptides ; 17(4): 601-7, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8804068

RESUMEN

The role of aminopeptidase A (APA) in inactivating cholecystokinin (CCK-8) was investigated in in vitro and in vivo experiments. EC 33 (3-amino-4-thio-butyl sulfonate), a selective APA inhibitor, decreased the formation of CCK7 after incubation of CCK-8 with rat brain synaptic membranes. The Km of purified APA for CCK-8, determined by quantifying CCK-7 production, was 144 microM and the Kcat 1400 s-1 . EC 33 protected endogenous CCK-like immunoreactivity (CCK-LI) released from brain slices by evoked depolarizations. The serine/thiol protease inhibitor Ala-Ala-Pro-Val-COCH2Cl (AAPV), alone or in combination with EC 33, did not modify significantly the level of CCK-LI released from the hippocampus, whereas it weakly protected the CCK-LI released from the cortex. Intracerebroventricular coadministration of CCK-8 and EC 33 in mouse brain led to a significant increase in the apparent affinity of CCK-8 as determined by the inhibition of the selective CCKB receptor agonist binding [3H]pBC 264 (ID50 = 88 pmol vs. 8250 pmol for CCK-8 alone); AAPV was less potent (ID50 = 445 pmol). In the same experiment the ID50 of pCCK-8, protected from aminopeptidases by a propionyl group was 86 pmol. These results strongly suggest that APA plays a major role in the inactivating pathway of CCK-8.


Asunto(s)
Aminopeptidasas/metabolismo , Encéfalo/metabolismo , Sincalida/metabolismo , Sincalida/farmacología , Membranas Sinápticas/metabolismo , Aminopeptidasas/antagonistas & inhibidores , Animales , Corteza Cerebral/metabolismo , Ventrículos Cerebrales/efectos de los fármacos , Ventrículos Cerebrales/fisiología , Glutamil Aminopeptidasa , Hipocampo/metabolismo , Técnicas In Vitro , Inyecciones Intraventriculares , Cinética , Masculino , Ratones , Inhibidores de Proteasas/farmacología , Ratas , Ratas Sprague-Dawley , Sincalida/administración & dosificación , Ácidos Sulfónicos/farmacología
17.
Mutat Res ; 246(1): 159-68, 1991 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1986260

RESUMEN

Rats fed with either a sufficient-vitamin A or a vitamin A-free diet were pretreated with 750 mg/kg body weight of retinyl palmitate, alpha-tocopherol acetate, ascorbic acid or glutathione. Benzo[a]pyrene (BaP) metabolism and BaP-induced mutagenesis in Salmonella typhimurium TA98 were investigated and related to lipid peroxidation activities in postmitochondrial (S9) liver fraction. The microsomal mixed-function oxidase activities were decreased by vitamin A deficiency and weakly affected by scavenger treatment. The rate of lipid peroxidation of microsomal membranes was unaffected by vitamin A deficiency because of decreased polyunsaturated fatty acids and increased vitamin E contents. However, lipid peroxidation was decreased by pretreatment with fat-soluble vitamins (chiefly vitamin E) and increased by ascorbic acid. Within each experimental group both BaP metabolism and BaP mutagenic activity were closely correlated with the rate of lipid peroxidation. In vitamin A deficiency, the increased BaP metabolism and mutagenicity could be related to a decrease in cytosolic contents of scavengers (vitamin A and glutathione). In Ames test conditions, the free radical pathway became a route for BaP metabolism and thus the BaP activation to mutagenic metabolites is related to the cellular status in free radical scavengers.


Asunto(s)
Ácido Ascórbico/farmacología , Glutatión/farmacología , Peroxidación de Lípido/efectos de los fármacos , Deficiencia de Vitamina A/metabolismo , Vitamina A/farmacología , Vitamina E/farmacología , Animales , Benzo(a)pireno/efectos adversos , Benzo(a)pireno/metabolismo , Sistema Enzimático del Citocromo P-450/análisis , Ácidos Grasos/análisis , Glutatión Transferasa/biosíntesis , Crecimiento/efectos de los fármacos , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Microsomas/química , Microsomas/efectos de los fármacos , Pruebas de Mutagenicidad , Tamaño de los Órganos , Ratas , Ratas Endogámicas
18.
Domest Anim Endocrinol ; 23(1-2): 87-100, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12142229

RESUMEN

Sheep in temperate latitudes are seasonal breeders. Of the different seasonal cues, photoperiod is the most reliable parameter and is used by animals as an indication of the time of the year to synchronize endogenous annual rhythms of reproduction and physiology. The photoperiodic information is transduced into neuroendocrine changes through variations in melatonin secretion from the pineal gland. Melatonin triggers variations in the secretion of luteinizing hormone-releasing hormone, luteinizing hormone and follicle stimulating hormone (LHRH/LH/FSH) responsible for seasonal changes in reproductive activity. In female sheep, the seasonal changes in the hormonal LH pattern mainly reflect an increase in the negative feedback exerted by estradiol under long days on the frequency of pulsatile LH secretion. The resulting seasonal inhibition of LH secretion involves the activation of monoaminergic and especially dopaminergic systems by estradiol. Other types of physiological regulation subject to seasonal changes such as voluntary food intake (VFI), fat metabolism, body mass and pelage growth also occur in sheep, goats or related wild species. Several neuroendocrine intermediates seem to be shared by these different systems and may participate in their synchronization, providing the advantage that this helps mammalian species to adapt to their environment.


Asunto(s)
Sistemas Neurosecretores/fisiología , Estaciones del Año , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dopamina/farmacología , Estradiol/farmacología , Hormona Liberadora de Gonadotropina/fisiología , Melatonina/fisiología , Fotoperiodo , Prolactina/fisiología , Reproducción
19.
J Neuroendocrinol ; 24(5): 798-808, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22512326

RESUMEN

GPR50, formerly known as melatonin-related receptor, is one of three subtypes of the melatonin receptor subfamily, together with the MT(1) and MT(2) receptors. By contrast to these two high-affinity receptor subtypes and despite its high identity with the melatonin receptor family, GPR50 does not bind melatonin or any other known ligand. Specific and reliable immunological tools are therefore needed to be able to elucidate the physiological functions of this orphan receptor that are still largely unknown. We have generated and validated a new specific GPR50 antibody against the ovine GPR50 and used it to analyse the neuroanatomical distribution of the GPR50 in sheep, rat and mouse whole brain. We demonstrated that GPR50-positive cells are widely distributed in various regions, including the hypothalamus and the pars tuberalis of the pituitary, in all the three species studied. GPR50 expressing cells are abundant in the dorsomedial nucleus of the hypothalamus, the periventricular nucleus and the median eminence. In rodents, immunohistochemical studies revealed a broader distribution pattern for the GPR50 protein. GPR50 immunoreactivity is found in the medial preoptic area (MPA), the lateral septum, the lateral hypothalamic area, the bed nucleus of the stria terminalis, the vascular organ of the laminae terminalis and several regions of the amygdala, including the medial nuclei of amygdala. Additionally, in the rat brain, GPR50 protein was localised in the CA1 pyramidal cell layer of the dorsal hippocampus. In mice, moderate to high numbers of GPR50-positive cells were also found in the subfornical organ. Taken together, these results provide an enlarged distribution of GPR50 protein, give further insight into the organisation of the melatoninergic system, and may lay the framework for future studies on the role of the GPR50 in the brain.


Asunto(s)
Encéfalo/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Roedores/metabolismo , Ovinos/metabolismo , Factores de Edad , Animales , Encéfalo/anatomía & histología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/fisiología , Conejos , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/fisiología , Roedores/anatomía & histología , Roedores/genética , Ovinos/anatomía & histología , Ovinos/genética , Distribución Tisular
20.
Animal ; 5(3): 329-36, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22445399

RESUMEN

Spontaneous ovulatory activity (SOA) in spring has been used to study the out-of-season breeding ability of Merinos d'Arles (MA) ewes. Within this breed, an association was found between more intense seasonality and genotype -/- at a MnlI restriction site (allele - for its absence v. + for its presence) in Exon II of the MT1 receptor gene. This study was designed to ascertain whether this association results in a direct effect of the MT1 genotype on the expression of seasonality in MA ewes. In the first year of the study, genotyping of 314 MA ewes at locus MnlI was carried out and resulted in frequencies of 43.0%, 44.9% and 12.1% for genotypes +/+, +/- and -/-, respectively. The SOA of these ewes was determined in early April of two consecutive years by assaying plasma progesterone concentrations in two blood samples taken 9 days apart. Groups of 30 ewes of each homozygous genotype (+/+ and -/-) were identified from this population and their SOA was followed by taking blood samples at regular intervals between January and mid-April of the second and third year of the study. In the second year, groups of ewes were managed together on rangelands, whereas in the third year each group was split into two subgroups given differential feed levels. The results clearly showed that genotype had no significant effect on SOA during the 2- to 3-month period preceding the introduction of rams for spring mating. In the second year of the study, in which the experimental procedure allowed a fair comparison of the fertility of ewes in spring mating, fertility was similar for both genotypes. The reciprocity of the association was not demonstrated and the MnlI polymorphic site could not be used as a genetic marker of selection for out-of-season breeding ability, at least not in the MA breed. The percentage of cycling ewes significantly decreased between January and April, and older ewes (5 or 6 years old depending on the year of the study) were more cyclic than younger ones (2 and 3 years old, respectively). The differential feeding level of ewes from early February did not significantly affect their SOA during the time period studied in the third year of the study.

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