[The therapy of endometriosis. New prospects]. / La terapia dell'endometriosi. Nuove prospettive.

Surgery is still the first line of therapy for endometriosis. At present, medical therapy is mostly indicated for treatment and prevention of recurrences. Current pharmacological regimens induce a hypoestrogenic state; this effect tends, on one hand, to inhibit the growth of endometriotic implants while, on the other hand, it significantly interferes with the integrity of the hypothalamus-pituitary-ovarian axis. The aim of this study is to review current knowledge on the new experimental therapeutic approaches to the disease. English articles on this topic have been searched by Medline. A particular attention has been paid to experimental therapeutic interventions supported by in vivo results. Three different novel strategies have been identified: 1) To act on estrogenic dependence of endometriosis using new drugs such as aromatase inhibitors and raloxifene. These drugs may have the advantage to act more specifically on the disease. 2) To treat the disease with immuno-modulators and anti-inflammatory drugs. These compounds may be helpful in both limiting the growth of endometriotic implants and in controlling the symptoms of the disease. 3) To prevent adhesion reformation after surgical lysis. Adhesions are an important hallmark of endometriosis which cannot be adequately eliminated by surgery. The use of barrier and fluid agents after surgical lysis seems to be effective in this regard. Results from studies aimed to investigate the effectiveness of these approaches are appealing. However, controlled clinical trials are now required to appropriately determine their real benefits and their specific indications.

Galanin receptor antagonists decrease fat preference in Brattleboro rat.

The Brattleboro rat eats spontaneously 46% of its diet per day in fat when given a choice of carbohydrate, protein and fat. An overexpression of galanin (GAL) has been also observed in the hypothalamic paraventricular nuclei (PVN). This associative correlation has led to a hypothesis of a functional relation between central galanin expression and the preference for a lipid diet. In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated. Both antagonists were injected into either the cerebral ventricles or directly above the PVN, and the diet consumption followed for the subsequent 24h. C7 decreased significantly fat consumption when injected into the ventricles or directly above the PVN. In contrast, galantide must be injected above the PVN to show the same effect. However, the two antagonists did not modify GAL mRNA expression in the PVN when they were injected 2h before sacrifice. These experiments confirm a functional link between the preferential consumption of fat and hypothalamic Galanin; different subtypes of the GAL receptor are probably involved, since both Galanin antagonists were differently efficient in decreasing spontaneous fat selection of the Brattleboro rat.

Dietary preferences of Brattleboro rats correlated with an overexpression of galanin in the hypothalamus.

Galanin (GAL) is a neuropeptide cosynthesized with vasopressin (AVP) in neurons of the hypothalamo-neurohypophysial system. It increases food intake when injected into the brain and elicits an overconsumption of fat. The Brattleboro rat (DI) is genetically unable to produce AVP; the AVP-deficient-producing neurons of the hypothalamo-neurohypophysial system of DI rats are chronically stimulated and DI rats suffer from diabetes insipidus. We studied the central expression of GAL and the dietary preferences in the DI rat. GAL was overexpressed in the hypothalamus of the DI rat. GAL mRNA was higher by 1.8-fold in the supraoptic (P < 0.05) and by four-fold in the paraventricular nuclei (P < 0.001) of male and female DI rats compared with those of control Long Evans (LE) rats. However, GAL mRNA was lower in the arcuate nuclei of DI rats and equal to that of LE rats in the dorsomedian nuclei. We also measured a high preference for a lipid diet (45% of the daily consumption) when DI rats ate from a choice of the three macronutrients. Chronic infusion with deamino-8D-AVP (agonist of AVP V2 receptors) prevented the diabetes insipidus and the chronic stimulation of the hypothalamo-neurohypophysial system of the DI rats. However, the treatment did not suppress the overexpression of GAL, nor did it affect the rats' preference for a lipid diet. We conclude that the DI rat provides a novel animal model in which a spontaneous dietary preference correlates with the overexpression of one of the hypothalamic peptides, GAL.