Tensión arterial y masa corporal en mujeres infértiles con síndrome de ovario poliquístico y su relación con el perfil hormonal / Blood pressure and body mass in infertile women polycystic ovary syndrome and its relation to the profile hormone

Objetivo: Evaluar perfil hormonal, índice de masa corporal y tensión arterial en 40 mujeres infértiles con ovario poliquístico. Métodos: En la consulta del Centro de Atención Integral de la Universidad de Los Andes se valoró talla, peso y tensión arterial. Durante la fase folicular del ciclo menstrual en ellas se midió en sangre las hormonas sexuales e insulina (basal y 2 horas poscarga glucosada) por electroquimioluminiscencia. Resultados: El índice de masa corporal se correlacionó directamente con el valor de tensión arterial sistólica, la relación LH/FSH y la testosterona sérica; e inversamente con las hormonas FSH y PRL. Los datos clínicos y de laboratorio se observaron dentro de los límites de referencia; sin embargo, la testosterona guardó relación directa con LH/FSH, índice de masa corporal y tensión arterial sistólica. Al compararse dos grupos de paciente con base al valor de la mediana poblacional, los grupos masa corporal > 24 kg/m2 y tensión arterial sistólica >120 mmHg mostraron niveles de DHEA-S e insulina (basal y 2 h) más elevados que en mujeres con índice de masa corporal y tensión arterial sistólica más bajos. Conclusiones: Existe correlación entre niveles séricos de andrógenos con sobrepeso e hipertensión arterial por mecanismos etiológicos interrelacionados. Síndrome de ovario poliquístico es de origen multicausal eventualmente con hiperandrogenemia. La falla metabólica debe controlarse en estas pacientes, lo que permitiría bajar el efecto de los andrógenos y favorecer el estado de fertilidad, pero sobre evita a largo plazo complicaciones como obesidad, diabetes mellitus tipo 2 e hipertensión arterial.

Objective: To evaluate hormonal profile, body mass index and blood pressure in 40 infertile women with polycystic ovary. Methods: In the out patien clinic of the Centro de Atencion Integral de la Universidad de Los Andes, height, weight and blood pressure were assessed. During follicular phase of the menstrual cycle in blood of them sex hormones and insulin (basal, 2 hours post glucose load) were measured by electrochemiluminescence. Results: The body mass index was directly correlated with the value of systolic blood pressure, ratio LH/ FSH and testosterone in serum, and it was inversely correlated with the hormones FSH and PRL. Clinical and laboratory data were observed within the reference limits, but kept directly related to testosterone LH / FSH, BMI and systolic blood pressure. When comparing two patient groups based on the value of the population median, body mass groups > 24 kg/m2 and systolic blood pressure > 120 mmHg, they showed levels of DHEA- S and insulin (basal and 2 h) higher than those women with lower values of BMI and systolic blood pressure. Conclusions: There is a correlation between serum androgen levels with overweight and hypertension by aetiological mechanisms interrelated. Polycystic ovary syndrome is multicausal origin eventually with hyperandrogenemia. Metabolic failure should be monitored in these patients, which would lower the effect of androgens and promote fertility status, but prevents long-term complications such as obesity, type 2 diabetes mellitus and high blood pressure.

Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors.

Ras signaling elicits diverse outputs, yet how Ras specificity is generated remains incompletely understood. We demonstrate that Wingless (Wg) and Decapentaplegic (Dpp) confer competence for receptor tyrosine kinase-mediated induction of a subset of Drosophila muscle and cardiac progenitors by acting both upstream of and in parallel to Ras. In addition to regulating the expression of proximal Ras pathway components, Wg and Dpp coordinate the direct effects of three signal-activated (dTCF, Mad, and Pointed-functioning in the Wg, Dpp, and Ras/MAPK pathways, respectively) and two tissue-restricted (Twist and Tinman) transcription factors on a progenitor identity gene enhancer. The integration of Pointed with the combinatorial effects of dTCF, Mad, Twist, and Tinman determines inductive Ras signaling specificity in muscle and heart development.

Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm.

Mesodermal progenitors arise in the Drosophila embryo from discrete clusters of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-function and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of unique combinations of intercellular signals. Initially, the intersection between the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two receptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor receptor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By monitoring the expression of the diphosphorylated form of mitogen-associated protein kinase (MAPK), we found that these RTKs are activated in small clusters of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localized RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreover, DER and Htl are differentially involved in the specification of particular progenitors. We conclude that distinct cellular identity codes are generated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in the progressive determination of embryonic mesodermal cells.

Signalling by the Drosophila epidermal growth factor receptor is required for the specification and diversification of embryonic muscle progenitors.

Muscle development initiates in the Drosophila embryo with the segregation of single progenitor cells, from which a complete set of myofibres arises. Each progenitor is assigned a unique fate, characterized by the expression of particular identity genes. We now demonstrate that the Drosophila epidermal growth factor receptor provides an inductive signal for the specification of a large subset of muscle progenitors. In the absence of the receptor or its ligand, SPITZ, specific progenitors fail to segregate. The resulting unspecified mesodermal cells undergo programmed cell death. In contrast, receptor hyperactivation generates supernumerary progenitors, as well as the duplication of at least one SPITZ-dependent myofibre. The development of individual muscles is differentially sensitive to variations in the level of signalling by the epidermal growth factor receptor. Such graded myogenic effects can be influenced by alterations in the functions of Star and rhomboid. In addition, muscle patterning is dependent on the generation of a spatially restricted, activating SPITZ signal, a process that may rely on the localized mesodermal expression of RHOMBOID. Thus, the epidermal growth factor receptor contributes both to muscle progenitor specification and to the diversification of muscle identities.

Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila.

We have isolated and characterized mutations in Drosophila neurotactin, a gene that encodes a cell adhesion protein widely expressed during neural development. Analysis of both loss and gain of gene function conditions during embryonic and postembryonic development revealed specific requirements for neurotactin during axon outgrowth, fasciculation, and guidance. Furthermore, embryos of some double mutant combinations of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy. This result provides evidence for functional cooperativity in vivo between the adhesion and signaling pathways controlled by neurotactin and the other three genes.

Inscuteable and numb mediate asymmetric muscle progenitor cell divisions during Drosophila myogenesis.

Each larval hemisegment comprises approximately 30 uniquely specified somatic muscles. These derive from muscle founders that arise as distinct sibling pairs from the division of muscle progenitor cells. We have analyzed the progenitor cell divisions of three mesodermal lineages that generate muscle (and pericardial cell) founders. Our results show that Inscuteable and Numb proteins are localized as cortical crescents on opposite sides of dividing progenitor cells. Asymmetric segregation of Numb into one of the sibling myoblasts depends on inscuteable and is essential for the specification of distinct sibling cell fates. Loss of numb or inscuteable results in opposite cell fate transformations-both prevent sibling myoblasts from adopting distinct identities, resulting in duplicated or deleted mesodermal structures. Our results indicate that the muscle progenitor cell divisions are intrinsically asymmetric; moreover, the involvement of both inscuteable and numb/N suggests that the specification of the distinct cell fates of sibling myoblasts requires intrinsic and extrinsic cues.

Lethal of scute, a proneural gene, participates in the specification of muscle progenitors during Drosophila embryogenesis.

The mechanisms that underlie the segregation of muscle founder cells in the Drosophila embryo are undefined. We show that the proneural gene lethal of scute (l'sc) is expressed in clusters of cells in the somatic mesoderm, from which individual muscle progenitors are singled out by progressive restriction of l'sc expression. Coexpression of l'sc and S59 (a putative muscle identity gene) in a subset of muscle progenitors shows that muscle founders are produced by division of muscle progenitors. In neurogenic mutant embryos the restriction of l'sc expression fails and all cells in a cluster coexpress l'sc and S59. Loss-of-function and overexpression phenotypes indicate a role for l'sc in the segregation of muscle progenitors and the formation of the muscle pattern.

Neurogenic genes control gene expression at the transcriptional level in early neurogenesis and in mesectoderm specification.

The development of the central nervous system in the Drosophila embryo is initiated by the acquisition of neural potential by clusters of ectodermal cells, promoted by the activity of proneural genes. Proneural gene function is antagonized by neurogenic genes, resulting in the realization of the neural potential in a single cell per cluster. To analyse the relationship between proneural and neurogenic genes, we have studied, in specific proneural clusters and neuroblasts of wild-type and neurogenic mutants embryos, the expression at the RNA and protein levels of lethal of scute, the most important known proneural gene in central neurogenesis. We find that the restriction of lethal of scute expression that accompanies the restriction of the neural potential to the delaminating neuroblast is regulated at the transcriptional level by neurogenic genes. These genes, however, do not control the size of proneural clusters. Moreover, available antibodies do not provide evidence for an hypothetical posttranscriptional regulation of proneural proteins by neurogenic genes. We also find that neurogenic genes are required for the specification of the mesectoderm. This has been shown for neuralized and Notch, and could also be the case for Delta and for the Enhancer of split gene complex. Neurogenic genes would control at the transcriptional level the repression of proneural genes and the activation of single-minded in the anlage of the mesectoderm.