ABSTRACT
PURPOSE: To evaluate genes differentially expressed in ovaries from lean (wild type) and obese (ob/ob) female mice and cyclic AMP production in both groups. METHODS: The expression on messenger RNA levels of 84 genes concerning obesity was analyzed through the PCR array, and cyclic AMP was quantified by the enzyme immunoassay method. RESULTS: The most downregulated genes in the Obesity Group included adenylate cyclase-activating polypeptide type 1, somatostatin, apolipoprotein A4, pancreatic colipase, and interleukin-1 beta. The mean decrease in expression levels of these genes was around 96, 40, 9, 4.2 and 3.6-fold, respectively. On the other hand, the most upregulated genes in the Obesity Group were receptor (calcitonin) activity-modifying protein 3, peroxisome proliferator activated receptor alpha, calcitonin receptor, and corticotropin-releasing hormone receptor 1. The increase means in the expression levels of such genes were 2.3, 2.7, 4.8 and 6.3-fold, respectively. The ovarian cyclic AMP production was significantly higher in ob/ob female mice (2,229±52 fMol) compared to the Control Group (1,814±45 fMol). CONCLUSIONS: Obese and anovulatory female mice have reduced reproductive hormone levels and altered ovogenesis. Several genes have their expression levels altered when leptin is absent, especially adenylate cyclase-activating polypeptide type 1. .
OBJETIVO: Avaliar os genes diferencialmente expressos em ovários de camundongos fêmeas magras (tipo selvagem) e obesas (ob/ob) e a produção de AMP cíclico em ambos os grupos. MÉTODOS: A expressão nos níveis de RNA mensageiro de 84 genes relacionados à obesidade foi analisada por PCR Array, e o AMP cíclico foi quantificado por método imunoenzimático. RESULTADOS: Os genes que mais sofreram diminuição da expressão no Grupo Obesidade incluíram o tipo 1 de polipeptídeo ativador da adenilato ciclase, o da somatostatina, da apolipoproteína A4, da colipase pancreática e da beta interleucina 1. A média de redução na expressão desses genes foi de aproximadamente 96, 40, 9, 4,2 e 3,6 vezes, respectivamente. Por outro lado, os genes que mais tiveram aumento na expressão no Grupo Obesidade foram o gene da proteína modificadora da atividade do receptor de calcitonina 3, do proliferador de peroxissomos ativados por proteína alfa, do receptor de calcitonina e do receptor para hormônio liberador de corticotropinas 1. As médias de acréscimo nos níveis de expressão de tais genes foram de 2,3, 2,7, 4,8 e 6,3 vezes, respectivamente. A produção de AMP cíclico ovariana foi significantemente aumentada em camundongos fêmeas ob/ob (2.229±52 fMol) quando comparada ao Grupo Controle (1.814±45 fMol). CONCLUSÕES: Camundongos fêmeas obesas e anovuladoras possuem níveis de hormônio reprodutivo reduzidos e ovulogênese alterada. Vários genes mostram níveis de expressão alterados quando a leptina está ausente, principalmente o tipo 1 de polipeptídeo ativador da adenilato ciclase. .
Subject(s)
Animals , Female , Mice , Anovulation/genetics , Anovulation/metabolism , Cyclic AMP/biosynthesis , Obesity/genetics , Obesity/metabolism , Mice, Inbred C57BL , Mice, ObeseABSTRACT
Dopamine receptor type 3 (DRD3) expressed in the limbic system sites involved in the regulation of GnRH seems to play a role in neuroendocrine control. We hypothesized that women with chronic anovulation should show exacerbated secretion of prolactin (PRL) after thyrotropin-releasing hormone (TRH) stimulation test, having more chances for dopamine inhibitory dysfunction due to alterations in the structure of DRD3. The DRD3-coding region was evaluated in 60 women with chronic anovulation (35 without and 25 with hyperresponse of PRL after TRH stimulation), and in 34 controls. Statistically similar frequencies of homozygous AGC polymorphism (43.4 and 33.4%) and heterozygous polymorphism (33.4 and 47.9%) at position 9 were found in controls and patients, respectively. Homozygous GCG polymorphism at position 17 was identified in 3.4% Type 3 dopaminergic receptor in chronic anovulationof the patients, while heterozygosis occurred in 20.8% of the patients and in 6.6% of the controls. The novel 41563_41567delTAAGT polymorphismof DRD3 was identified in 14.7% of the controls and 8.6% of the women with chronic anovulation displaying hyperresponse of PRL after TRH stimulation. Alteration 41563_41567delTAAGT of DRD3 was not found in patients who did not show hyperresponse of PRL after TRH stimulation. Normal baseline and peak levels of PRL and thyroid-stimulating hormone were similar for women with and without 41563_41567delTAAGT in the DRD3 gene. It is concluded that the novel polymorphism in DRD3 identified in this study is not associated with the response of PRL to TRH stimulation in women with chronic anovulation.