Contrôle génique par l’estradiol, application à l’angiœdème

The usual types I and II of hereditary angioedema (HAE) are related to mutations on the complement C1 inhibitor gene (SERPING1). These remain rare diseases and, in a certain number of cases, are worsened by estrogens. Another type has been described more recently and called “estrogen-dependent inherited form of angioedema” or type III. The clinical symptoms and the physiopathology are polymorphic. Deregulated bradykinin production is the common feature of HAE. Estrogens bind to specific receptors. The hormone–receptor complexes can activate the transcription of genes through binding to specific sequences of the DNA. Most of the steps are involved in bradykinin metabolism. Its production, the B2 receptor expression and its degradation can be controlled by estrogens at the molecular level. It was indeed shown that C1 inhibitor, the Hageman factor, kininogen, plasma and tissue kallikreins, B2 receptors and some enzymes involved in their catabolism are targets for the estrogens. These observations have some direct implications for contraception in the women with HAE. Estrogen containing pills are contra-indicated, whereas the various contraceptive progestins or IUD can be used. Concerning postmenopausal symptomatic women, estrogens are contra-indicated, whereas progestins and tibolone can help to alleviate the climacteric symptoms.