Involvement of neurosteroids in the control of hypothalamic-pituitary-adrenal axis activity in pregnant sheep under basal and stressful conditions.

Neurosteroids are synthesized locally in the brain, where they can modify neuronal functionality depending on the physiological state. A high correlation was demonstrated between the increasing activity of the hypothalamic-pituitary-adrenal (HPA) axis and allopregnanolone (AL) concentration in the cerebrospinal fluid in sheep during pregnancy. Therefore, the present study tested the hypothesis that blocking neurosteroid synthesis in the brain of a pregnant sheep would affect HPA axis activity under both basal and stressful conditions. Two groups of sheep in the fourth month of gestation (n = 7 each) were subjected to the following treatments: 1) intracerebroventricular (icv) infusion of vehicle for three days (C) and then icv infusion of finasteride (a total of 100 µg/240 µL/day) for three days (F), one week apart, and 2) icv infusion of vehicle for three days and application of stressful stimuli (isolation and partial movement restriction) on the third day (S), and subsequently icv infusion of finasteride for three days and application of stressful stimuli on the third day (SF), one week apart. On the third days of the experiment, a 4-h push-pull perfusion of the infundibular nucleus/median eminence and blood sampling were performed. Mean perfusate corticotropin-releasing hormone (CRH), plasma adrenocorticotropin (ACTH) and cortisol concentrations were significantly higher in sheep treated with finasteride, stress and finasteride in combination with stress compared to controls. The highest hormone concentrations in Groups F, S and SF, were recorded during the first 60 min; however, significant increases in CRH and ACTH levels were observed in Group SF towards the end of the experiment. It can be concluded that neurosteroids may be an essential component of the mechanism controlling HPA axis activity in pregnant sheep, not only under stress-free conditions, but more importantly, also by inhibiting the neuroendocrine response to stressors.