RESUMEN

The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3'-hydroxy-3'-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression.

Asunto(s)

Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Ácido Mevalónico/metabolismo , Proteína p53 Supresora de Tumor/fisiología , Línea Celular Tumoral , Colesterol/biosíntesis , Regulación Neoplásica de la Expresión Génica , Humanos , Redes y Vías Metabólicas , Regiones Promotoras Genéticas , Transcripción Genética

RESUMEN

Here we show that replicative senescence in normal human diploid IMR90 fibroblasts is accompanied by altered expression of a set of microRNAs (miRNAs) (senescence-associated miRNAs), with 14 and 10 miRNAs being either up or downregulated (>2-fold), respectively, in senescent with respect to young cells. The expression of most of these miRNAs was also deregulated upon senescence induced by DNA damage (etoposide) or mild oxidative stress (diethylmaleate). Four downregulated miRNAs were part of miRNA family-17, recently associated to human cell and tissue aging. Moreover, eight upregulated and six downregulated miRNAs mapped in specific chromosomal clusters, suggesting common transcriptional regulation. Upon adoptive overexpression, seven upregulated miRNAs induced the formation of senescence-associated heterochromatin foci and senescence-associated ß-galactosidase staining (P<0.05), which was accompanied, in the case of five of them, by reduced cell proliferation. Finally, miR-210, miR-376a(*), miR-486-5p, miR-494, and miR-542-5p induced double-strand DNA breaks and reactive oxygen species accumulation in transfected cells. In conclusion, we have identified a set of human miRNAs induced during replicative and chemically induced senescence that are able to foster the senescent phenotype by prompting DNA damage.

Asunto(s)

Senescencia Celular/fisiología , Fibroblastos/metabolismo , Regulación de la Expresión Génica/fisiología , MicroARNs/biosíntesis , Transcripción Genética/fisiología , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Células Cultivadas , Senescencia Celular/efectos de los fármacos , Roturas del ADN de Doble Cadena , Diploidia , Etopósido/farmacología , Fibroblastos/citología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Maleatos/farmacología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Transcripción Genética/efectos de los fármacos

Asunto(s)

Envejecimiento/genética , Técnicas de Cultivo de Célula/métodos , Células Cultivadas/metabolismo , Senescencia Celular/genética , Fibroblastos/metabolismo , Regulación de la Expresión Génica/genética , ARN Mensajero/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Ciclo Celular/genética , Células Cultivadas/citología , Niño , Regulación hacia Abajo/genética , Feto , Fibroblastos/citología , Humanos , Oxidantes , Fenotipo , ARN Mensajero/genética

RESUMEN

In this study we addressed the question of the intracellular localization of Fe65, an adaptor protein interacting with the beta-amyloid precursor protein (APP) and with the transcription factor CP2/LSF/LBP1. By using tagged Fe65 expression vectors, we observed that a significant fraction of Fe65 is localized in the nucleus of transfected COS7 cells. Furthermore, the isolation of nuclei from untransfected PC12 cells allowed us to observe that a part of the endogenous Fe65 is present in the nuclear extract. The analysis of Fe65 mutant constructs demonstrated that the region of the protein required for its nuclear translocation includes the WW domain, and that, on the other hand, a small fragment of 100 residues, including this WW domain, contains enough structural information to target a reporter protein (green fluorescent protein (GFP)-GFP) to the nucleus. To evaluate whether the Fe65-APP interaction could affect Fe65 intracellular trafficking, COS7 cells were cotransfected with APP(695) or APP(751) and with GFP-Fe65 expression vectors. These experiments demonstrated that Fe65 is no longer translocated to the nucleus when the cells overexpress APP, whereas the nuclear targeting of GFP-Fe65 mutants, unable to interact with APP, is unaffected by the coexpression of APP, thus suggesting that the interaction with APP anchors Fe65 in the cytosol.

Asunto(s)

Precursor de Proteína beta-Amiloide/fisiología , Citosol/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/metabolismo , Transporte Activo de Núcleo Celular , Animales , Transporte Biológico , Células COS , Membrana Celular/metabolismo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Células PC12 , Ratas , Proteínas Recombinantes de Fusión/metabolismo

RESUMEN

The metallothionein (MT)3 gene is expressed predominantly in the brain and the organs of the reproductive system, and fails to respond to metal ions in vivo. A CTG repeat was proposed to function as a potential repressor element in nonpermissive cells, and a sequence similar to the JC virus silencer element was found to function as a negative element in permissive primary astrocytes. The objective of this study was to characterize further the mechanisms governing cell-type specific MT-3 gene transcription. We searched for a suitable cell line expressing the MT-3 gene to be used for determination of MT-3 promoter tissue specificity, and showed that MT-3 expression is activated during neuroectodermal differentiation of P19 cells induced by retinoic acid to levels similar to those found in whole brain. Deletion of the CTG repeat or of the JC virus silencer did not promote MT-3 promoter activity in nonpermissive cells, or enhance expression in permissive cells. We identified MT-3 promoter sequences interacting with liver and brain nuclear proteins, as assayed by DNase I footprinting analyses and electrophoretic mobility shift assay, and assessed the role of these sequences in the regulation of MT-3 expression by cotransfection experiments. We generated stable transfectants in permissive C6 and nonpermissive NIH-3T3 cells, and analysed the methylation status of the MT-3 gene. These studies show that regulation of tissue-specific MT-3 gene expression does not appear to involve a repressor, and suggest that other mechanisms such as chromatin organization and epigenetic modifications could account for the absence of MT-3 gene transcription in nonpermissive cells.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Metalotioneína/genética , Ratones/genética , Neuronas/citología , Regiones Promotoras Genéticas/genética , Teratocarcinoma/patología , Células 3T3 , Animales , Secuencia de Bases , Células COS , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Chlorocebus aethiops , ADN/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metalotioneína/biosíntesis , Metalotioneína 3 , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Neoplasias/patología , Neoplasias Experimentales/patología , Neuroglía/citología , ARN Mensajero/biosíntesis , ARN Neoplásico/biosíntesis , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/biosíntesis , Especificidad de la Especie , Teratocarcinoma/genética , Activación Transcripcional , Transfección , Tretinoina/farmacología , Células Tumorales Cultivadas/efectos de los fármacos

RESUMEN

A distinctive tract of all the forms of Alzheimer's disease is the extracellular deposition of a 40-42/43 amino acid-long peptide derived from the so-called beta-amyloid precursor protein (APP). This is a membrane protein of unknown function, whose short cytosolic domain has been recently demonstrated to interact with several proteins. One of these proteins, named Fe65, has the characteristics of an adaptor protein; in fact, it possesses three protein-protein interaction domains: a WW domain and two PID/PTB domains. The interaction with APP requires the most C-terminal PID/PTB domain, whereas the WW domain is responsible for the interaction with various proteins, one of which was demonstrated to be the mammalian homolog of the Drosophila enabled protein (Mena), which in turn interacts with the cytoskeleton. The second PID/PTB domain of Fe65 binds to the CP2/LSF/LBP1 protein, which is an already known transcription factor. The other proteins interacting with the cytosolic domain of APP are the G(o) heterotrimeric protein, APP-BP1 and X11. The latter interacts with APP through a PID/PTB domain and possesses two other protein-protein interaction domains. The small size of the APP cytodomain and the overlapping of its regions involved in the binding of Fe65 and X11 suggest the existence of competitive mechanisms regulating the binding of the various ligands to this cytosolic domain. In this short review the possible functional roles of this complex protein network and its involvement in the generation of Alzheimer's phenotype are discussed.

Asunto(s)

Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/química , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas del Tejido Nervioso/química , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Animales , Citosol/metabolismo , Drosophila , Humanos , Unión Proteica

RESUMEN

We previously demonstrated that Fe65 protein is one of the ligands of the cytoplasmic domain of beta-amyloid precursor protein (APP). Another ligand of this molecule was recently identified; it is similar to Fe65, so it was named Fe65-like (Fe65L1). Herein we describe the cloning of another Fe65-like cDNA (Fe65L2), similar to Fe65 and to Fe65L1, which encodes a protein of approx. 50 kDa. Its cognate mRNA is expressed in various rat tissues, particularly in brain and testis. The three members of the Fe65 protein family share several structural and functional characteristics. The primary structures of the three proteins can be aligned in three regions corresponding to the protein-protein interaction domains of Fe65 [the protein-protein interaction domain containing two conserved tryptophan residues and the two phosphotyrosine interaction domain/phosphotyrosine binding (PID/PTB) domains], whereas the remaining sequences are poorly related. Like Fe65, Fe65L1 and Fe65L2 genes encode two different protein isoforms, derived from the alternative splicing of a very small exon of only six nucleotides, which results, within the N-terminal PID/PTB domain, in the presence or absence of two acidic/basic amino acids. Fe65L2 is able to interact, both in vitro and in vivo, with the intracellular domain of APP. Also, in the case of APP, another two closely related proteins exist, named beta-amyloid precursor-like protein (APLP)1 and APLP2: by using the interaction trap procedure we observed that both Fe65 and Fe65L2 interact with APP, APLP1 or APLP2, although with different efficiencies.

Asunto(s)

Precursor de Proteína beta-Amiloide/metabolismo , Proteínas Portadoras/metabolismo , Proteínas del Tejido Nervioso/fisiología , Proteínas Nucleares/fisiología , Fosfoproteínas/metabolismo , Empalme Alternativo , Secuencia de Aminoácidos , Precursor de Proteína beta-Amiloide/química , Animales , Proteínas Portadoras/aislamiento & purificación , Citoplasma/metabolismo , Ligandos , Datos de Secuencia Molecular , Peso Molecular , Fosfoproteínas/aislamiento & purificación , Unión Proteica , Ratas , Ratas Sprague-Dawley , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Distribución Tisular

RESUMEN

The two tandem phosphotyrosine interaction/phosphotyrosine binding (PID/PTB) domains of the Fe65 protein interact with the intracellular region of the Alzheimer's beta-amyloid precursor protein (APP). This interaction, previously demonstrated in vitro and in the yeast two hybrid system, also takes place in vivo in mammalian cells, as demonstrated here by anti-Fe65 co-immunoprecipitation experiments. This interaction differs from that occurring between other PID/PTB domain-containing proteins, such as Shc and insulin receptor substrate 1, and activated growth factor receptors as follows: (i) the Fe65-APP interaction is phosphorylation-independent; (ii) the region of the APP intracellular domain involved in the binding is larger than that of the growth factor receptor necessary for the formation of the complex with Shc; and (iii) despite a significant similarity the carboxyl-terminal regions of PID/PTB of Fe65 and of Shc are not functionally interchangeable in terms of binding cognate ligands. A role for Fe65 in the pathogenesis of familial Alzheimer's disease is suggested by the finding that mutant APP, responsible for some cases of familial Alzheimer's disease, shows an altered in vivo interaction with Fe65.

Asunto(s)

Enfermedad de Alzheimer/genética , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/metabolismo , Fosfotirosina/metabolismo , Secuencia de Aminoácidos , Precursor de Proteína beta-Amiloide/genética , Animales , Sitios de Unión , Células COS , Humanos , Datos de Secuencia Molecular , Células PC12 , Fosforilación , Mutación Puntual , Pruebas de Precipitina , Unión Proteica , Proteínas/metabolismo , Ratas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Relación Estructura-Actividad

RESUMEN

Fe65 is an adaptor protein that interacts with the Alzheimer beta-amyloid precursor protein and is expressed mainly in the neurons of several regions of the nervous system. The FE65 gene has a TATA-less promoter that drives an efficient transcription in cells showing a neuronal phenotype, whereas its efficiency is poor in non-neuronal cells. A short sequence encompassing the transcription start site contains sufficient information to drive the transcription in neuronal cells but not in non-neural cells. Electrophoretic mobility-shift assays performed with rat brain nuclear extracts showed that three major DNA-protein complexes, named BI, BII and BIII, are formed by the FE65 minimal promoter. The proteins present in complexes BI and BII were purified from bovine brain; internal microsequencing of the purified proteins demonstrated that they corresponded to the previously isolated single-stranded-DNA-binding protein Pur alpha, abundantly expressed in the brain. In Chinese hamster ovary (CHO) cells, where the efficiency of FE65 promoter is very low, transient expression of Pur alpha increased the transcription efficiency of the FE65 minimal promoter. By using oligonucleotide competition and a specific antibody we demonstrated that the transcription factor YY1 is responsible for the formation of complex BIII. Also in this case, the transient expression of the YY1 cDNA in CHO cells resulted in an increased transcription from the FE65 minimal promoter. The absence of any co-operative effect when CHO cells were co-transfected with both YY1 and Pur alpha cDNA species suggests that two different transcription regulatory mechanisms could have a role in the regulation of the FE65 gene.

Asunto(s)

Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Proteínas de Unión al ADN/fisiología , Proteínas del Tejido Nervioso/genética , Neuronas/metabolismo , Proteínas Nucleares/genética , Regiones Promotoras Genéticas/fisiología , Transactivadores/fisiología , Factores de Transcripción/fisiología , Animales , Células CHO , Bovinos , Cricetinae , Proteínas de Unión al ADN/metabolismo , Sinergismo Farmacológico , Factores de Unión al ADN Específico de las Células Eritroides , Unión Proteica/genética , Ratas , Factores de Transcripción/metabolismo , Factor de Transcripción YY1

RESUMEN

The FE65 gene encodes a nuclear protein of unknown function that is expressed in several areas of the rat nervous system during development and in the adult animal, particularly in somatic and visceral ganglia. FE65 mRNA is abundant in neuronal cell lines, whereas it is barely detectable in non-neuronal cells. We identified the two transcription start sites of the FE65 gene and we isolated the rat genomic fragment containing one of these two transcriptional start sites. We demonstrate that this fragment contains a promoter able to direct an efficient transcription of a reporter gene in PC12 cells and in NTERA2 cells upon their differentiation with retinoic acid, whereas it functions poorly in non-neuronal cells, such as Rat2 fibroblasts and BRL hepatocytes. This promoter is composed of two regions. The first includes a cis-element whose removal greatly decreases the transcriptional efficiency in all cells examined and which forms similar complexes with proteins from PC12 and Rat2 cells. This cis-element binds Sp1 or another GC-binding factor. The second cis-element encompasses the transcription start site and is still able to direct transcription only in neuronal cells. The DNA-protein complexes formed by this cis-element in neuronal cells differ from those formed in non-neuronal cells. The analysis of point mutations in this region indicates that the proteins that bind to this cis-element interact with both overlapping and distinct nucleotide sequences.

Asunto(s)

Proteínas del Tejido Nervioso/genética , Neuronas/fisiología , Proteínas Nucleares/genética , Regiones Promotoras Genéticas/genética , Transcripción Genética/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular , Clonación Molecular , Regulación de la Expresión Génica , Biblioteca Genómica , Datos de Secuencia Molecular , Mutación/fisiología , Proteínas del Tejido Nervioso/fisiología , Proteínas Nucleares/fisiología , Regiones Promotoras Genéticas/fisiología , Ratas , Proteínas Recombinantes de Fusión/biosíntesis , Especificidad de la Especie , Transactivadores/fisiología

RESUMEN

The major transcript of the FE65 gene is a neuron-specific mRNA that encodes a nuclear protein whose aminoterminal domain strongly activates the transcription of a reporter gene when fused to a heterologous DNA-binding domain. FE65 gene expression is regulated during neuronal differentiation of the NTERA-2 cell line, and it is temporally and spatially restricted during mouse embryo development. It is first detected around day 10 of gestation in the basal plate of the neural tube, and then, at the subsequent stages of development and in the newborn animals, it is found solely in neural structures. Its expression is most abundant in the neural crest derivatives (e.g. spinal and encephalic ganglia), ganglionic structures of sense organs (ganglionic layer of the retina and olfactory epithelium), as well as the ganglionic structures of the autonomic nervous system. Thus FE65 gene expression can be considered a marker of the development of embryo ganglionic derivatives.

Asunto(s)

Sistema Nervioso Autónomo/metabolismo , Encéfalo/metabolismo , Nervios Craneales/metabolismo , Desarrollo Embrionario y Fetal , Expresión Génica , Proteínas del Tejido Nervioso/biosíntesis , Neuronas/metabolismo , Proteínas Nucleares/biosíntesis , Médula Espinal/metabolismo , Animales , Sistema Nervioso Autónomo/embriología , Biomarcadores/análisis , Nervios Craneales/embriología , Femenino , Regulación de la Expresión Génica , Humanos , Hibridación in Situ , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/análisis , Neuronas/fisiología , Proteínas Nucleares/análisis , Embarazo , Ratas , Médula Espinal/embriología

RESUMEN

The levels of the mRNA corresponding to the intracellular binding proteins for retinoic acid and retinol (CRABP1 and CRBP1, respectively) were studied in primary cultures of somatic and germ cells of the rat seminiferous tubules. We show that the CRABP1 mRNA is expressed in Sertoli and germ cells and a single molecular species of mRNA is detected. CRBP1 mRNA is detected in Sertoli and peritubular cells. The regulation of the expression of both genes by retinoids was studied in Sertoli cells. CRABP1 mRNA levels are not affected by either retinoic acid or retinol, whereas both compounds positively regulate CRBP1 mRNA synthesis in a dose-dependent manner. A fivefold increase in CRBP1 mRNA levels was observed 32-48 h after addition of either agent. These results demonstrate that in Sertoli cells the expression of CRABP1 is not affected by retinoids, similar to the situation observed in vivo and in other in-vitro cultures. CRBP1-gene expression is, instead, induced and the variations in CRBP1-mRNA levels may regulate the intracellular concentrations of retinoids, as a response to changes in the vitamin-A nutritional status.

Asunto(s)

Proteínas Portadoras/genética , Regulación de la Expresión Génica/efectos de los fármacos , ARN Mensajero/metabolismo , Retinoides/farmacología , Proteínas de Unión al Retinol/genética , Túbulos Seminíferos/metabolismo , Animales , Células Cultivadas , Masculino , Ratas , Ratas Wistar , Receptores de Ácido Retinoico , Proteínas Celulares de Unión al Retinol , Túbulos Seminíferos/efectos de los fármacos , Células de Sertoli/metabolismo , Espermatozoides/metabolismo , Tretinoina/farmacología , Vitamina A/farmacología

Asunto(s)

Factor I del Crecimiento Similar a la Insulina/biosíntesis , Northern Blotting , Humanos , Células Híbridas , Transcripción Genética/genética

RESUMEN

The Retinol-Binding Protein (RBP) is expressed primarily in the liver. The regulatory elements involved in its tissue-specific expression have been identified and mapped to the 5' flanking region of the RBP gene. In this paper heterokaryons and somatic cell-hybrids have been produced and analysed in order to demonstrate that the RBP gene is subject to extinction and to identify the target sequences of this phenomenon. We show here that the gene is extinguished in fusions of hepatoma with a variety of cells of different species and embryonic lineages. The repression is not due to loss of the gene and occurs also when chromosome 10, where the gene is located, is inherited from the expressing parental cell-type. Hybrid clones were transfected with constructs carrying DNA segments of different lengths from the 5' flanking region of the RBP gene fused to a reporter gene. We demonstrate that extinction takes place also on an exogenous RBP-CAT gene, mimicking the phenomenon observed with the endogenous gene in its chromosomal location. Moreover, we identify and map the target sequences of the putative extinguishing function. Our data thus show that extinction of RBP is mediated through the DNA segment that is involved in its tissue-specific expression.

Asunto(s)

Regulación de la Expresión Génica , Proteínas de Unión al Retinol/genética , Animales , Secuencia de Bases , Northern Blotting , Southern Blotting , Línea Celular , Clonación Molecular , Genes , Células HeLa , Células Híbridas , Hígado/metabolismo , Especificidad de Órganos , Ratas , Transfección

RESUMEN

Protein deficiency leads to a decreased concentration of plasma proteins, although it is not clear whether this response is caused by alterations in gene transcription or in post-transcriptional events. The aim of this study was to investigate the expression of some liver-specific genes coding for plasma proteins in rats kept on a protein-free diet for 30 days. Cloned cDNA probes for the albumin, transthyretin, retinol-binding protein and prothrombin genes were used in Northern hybridizations to total liver RNA to compare their transcript levels in protein-deficient and control animals. Liver polysomes were also isolated and fractionated from the two groups of animals to examine the possible effects of protein deficiency on translation of the mRNAs. The results indicate that the albumin and transthyretin mRNAs are present in lower amounts in protein deficiency. The distribution profile along sucrose gradients shows that all mRNAs are undergoing translation, but in protein-deficient animals a small but consistent fraction of each mRNA is also present in the non-polysomal, low molecular weight fractions.

Asunto(s)

Proteínas Sanguíneas/genética , Hígado/fisiología , Desnutrición Proteico-Calórica/genética , Actinas/genética , Animales , Ferritinas/genética , Regulación de la Expresión Génica , Masculino , Polirribosomas/metabolismo , Prealbúmina/genética , Protrombina/genética , ARN Mensajero/genética , Ratas , Ratas Endogámicas , Proteínas de Unión al Retinol/genética , Proteínas Plasmáticas de Unión al Retinol , Albúmina Sérica/genética , Transcripción Genética

RESUMEN

The human gene coding for RBP4 has been assigned to 10q23----24 using a panel of somatic cell hybrids and in situ hybridization experiments. The mapping of the human RBP1, previously assigned by our group to chromosome 3 using a panel of somatic cell hybrids, was restricted to the region 3q21----22 using in situ experiments and Southern blots of genomic DNA from a hybrid retaining a portion of chromosome 3.

Asunto(s)

Cromosomas Humanos Par 3 , Proteínas de Unión al Retinol/genética , Southern Blotting , Mapeo Cromosómico , Humanos , Células Híbridas , Hibridación de Ácido Nucleico

Asunto(s)

Cromosomas Humanos Par 3 , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Proteínas de Unión al Retinol/genética , Mapeo Cromosómico , ADN/genética , Humanos , Proteínas Celulares de Unión al Retinol

RESUMEN

A cDNA clone coding for Cellular Retinol-Binding Protein (CRBP) was used as a probe to study the expression of the gene in the somatic cells of the seminiferous tubules (Sertoli and peritubular cells). In this paper we demonstrate that these cells are actively involved in the synthesis of the specific mRNA. In Sertoli cells the gene is modulated by the hormones effective in spermatogenesis, such as FSH and testosterone. Moreover, peritubular cells revealed an approximately two times higher concentration of CRBP steady-state mRNA levels when compared with Sertoli cells.

Asunto(s)

ARN Mensajero/genética , Proteínas de Unión al Retinol/genética , Túbulos Seminíferos/metabolismo , Células de Sertoli/metabolismo , Testículo/metabolismo , Animales , Células Cultivadas , Clonación Molecular , ADN/genética , Masculino , ARN Mensajero/aislamiento & purificación , Ratas , Ratas Endogámicas , Proteínas Celulares de Unión al Retinol