Modelo experimental de terapia hormonal e modeulação sexual na puberdade: hipogonadismo e hiperestrogenismo em ratos machos

Resumo (EN)

Imbalances in sexual hormone levels during puberty often have significant impacts on both human and animal health. Nevertheless, there remains a limited understanding of hormonal therapy in the context of feminization. In veterinary medicine, a consensus is yet to be reached regarding the optimal age for castration and its implications for the overall well-being of animals. To address these gaps, the current study introduced two rat models: one depicting hypogonadism during puberty through castration and another representing hyperestrogenism achieved through castration and estrogen administrations.

The primary objectives were to assess the pathophysiological and neurobiological mechanisms associated with hypogonadism and hyperestrogenism, and to establish a rat model specifically focused on hyperestrogenism. Pubertal rats were categorized into two groups: the hypogonadism group, subjected to castration, and the hyperestrogenism group, consisting of castrated rats treated weekly with estrogen. These rats were then evaluated for body weight gain and nasoanal length growth. Upon reaching adulthood, they underwent assessments in the sexual preference test, the light-dark test (anxiety study), and the forced swim test (depressive study). Various parameters such as tibial muscle weight, penis weight and length, expression of central glial fibrillary acidic protein (assessed through immunohistochemistry as a marker of astrocytic neuroinflammation), and retroperitoneal adipose tissue (measured through histometry) were also examined.

The hypogonadism model resulted in reduced nasoanal growth and penile weight and length, diminished social interaction with the opposite sex, induction of depressive-like behavior, increased adipose tissue, and heightened astrocytic expression in the frontal cortex. On the other hand, the hyperestrogenism model arrested weight gain and nasoanal growth, decreased tibial muscle and penis weight and length, reduced opposite-sex social interaction, increased same-sex social interaction, lowered self-grooming, induced antidepressant behavior, prevented hypogonadism-induced fat gain, and decreased astrocytic expression in the hypothalamus.

In conclusion, the hypogonadism model during puberty impaired physical development, increased fat accumulation, inhibited social/sexual interactions, and induced depressive-like behavior in rats, all of which were associated with neuroinflammation in the frontal cortex. The hyperestrogenism model further impaired physical development, albeit without affecting fat levels. It influenced behavior and modulated the social preference of the opposite sex towards the same sex, processes associated with reduced astrocytic expression in the hypothalamus. The hyperestrogenism model has proven to be a valuable tool for investigating hormonal therapy and feminization.