Anxiety disorders are one of the most prevalent mood disorders that can lead to impaired quality of life. Current treatment of anxiety disorders has various adverse effects, safety concerns, or restricted efficacy; therefore, novel therapeutic targets need to be studied. Sex steroid hormones (SSHs) play a crucial role in the formation of brain structures, including regions of the limbic system and prefrontal cortex during perinatal development. In the brain, SSHs have activational and organizational effects mediated by either intracellular or transmembrane G-protein coupled receptors. During perinatal developmental periods, the physiological concentrations of SSHs lead to the normal development of the brain; however, the early hormonal dysregulation could result in various anxiety diorders later in life. Sex differences in the prevalence of anxiety disorders suggest that SSHs might be implicated in their development. In this review, we discuss preclinical and clinical studies regarding the role of dysregulated SSHs signaling during early brain development that modifies the risk for anxiety disorders in a sex-specific manner in adulthood. Moreover, our aim is to summarize potential molecular mechanisms by which the SSHs may affect anxiety disorders in preclinical research. Finally, the potential effects of SSHs in the treatment of anxiety disorders are discussed.

• Klíčová slova
• brain structures, molecular mechanism, mood disorders, sex steroid receptors, testosterone,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Gonadal hormones have been well-known to affect brain regions known to be involved in the modulation of mood and affective-related behavior. Prenatal stress might alter hypothalamic-pituitary-gonadal axis, it could be a target for development of affective-related disorders in male offspring. The present study was designed to examine an anxiety-like behavior in the adult male offspring with low levels of endogenous androgens delivered from pregnant dams exposed to prenatal stress from gestation day 15 to gestation day 19. The non-stressed and prenatally stressed intact, gonadectomized (GDX) and GDX male offspring treated with oil solvent or testosterone propionate (TP, 0.5 mg/kg, s.c., 14 days, once daily) were used in all experiments. Anxiety-like behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT), respectively. Also, testosterone levels in the blood serum were measured in all experimental groups of offspring. Prenatally stressed GDX offspring demonstrated a significant decrease for time spent into the open arms and increase for time spent into the closed arms as compared to the non-stressed offspring. Administration of TP to the prenatally stressed GDX offspring resulted in a more markedly decrease of the time spent into the open arms and significantly raised the time spent into the closed arms as compared to the non-stressed GDX offspring treated with TP, non-stressed/prenatally stressed GDX offspring. Prenatally stressed GDX offspring showed a significant increase of crossing, rearing, grooming and defecation as compared to the prenatally stressed control offspring. On the contrary, administration of TP to the prenatally stressed GDX offspring significantly decreased crossing behavior, frequency of rearing and grooming behavior as compared to the non-stressed GDX offspring treated with TP, non-stressed/prenatally stressed GDX offspring. Prenatally stressed GDX offspring demonstrated a significant decrease of testosterone levels as compared to the non-stressed/prenatally stressed intact offspring, as well as non-stressed GDX offspring. Administration of TP significantly increased testosterone levels when prenatally stressed GDX offspring were compared with the prenatally stressed intact offspring, non-stressed/prenatally stressed GDX offspring. Thus, the results of the study clearly suggest that gonadectomy and TP supplementation profoundly changed an anxiety-related behavior in prenatally stressed male offspring in the EPM. Our current findings suggest that androgen deficiency in the prenatally stressed male offspring produces the high anxiety level and induces a marked anxious-like state. TP supplementation provokes development of profoundly anxious-like state in the prenatally stressed male offspring, Furthermore, this is the first study to show anxiogenic-like effect of TP administration on anxiety-related states in prenatally stressed male offspring with androgen deficiency.

• Klíčová slova
• Prenatal stress, anxiety, behavior, gonadectomy, male offspring, testosterone,
• Publikační typ
• časopisecké články MeSH