Temporal changes in the cerebrospinal fluid allopregnanolone concentration and hypothalamic-pituitary-adrenal axis activity in sheep during pregnancy and early lactation

Abstract

Research on pregnant mice and rats indicated that a neurosteroid allopregnanolone (AP) might have a stress-protective effect, decreasing the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Using a sheep model in the present research, we tested a hypothesis that the cerebrospinal fluid (CSF) AP concentration changes during pregnancy and early lactation, keeping in check the secretory activity of the HPA axis. Four-hour-long CSF collections (20 μL/min, from 10:00 to 14:00) from the third brain ventricle were conducted in 8 sheep, every 4 weeks, starting from the 28th day of pregnancy until the 28th day after delivery, to determine AP and corticotropin-releasing hormone (CRH) concentrations. A maximum of 8 samples (every 30 min) were gathered from individual sheep. Each series of CSF collections was accompanied by blood sampling every 10 min, to examine the distribution of mean plasma adrenocorticotropin (ACTH) and cortisol concentrations. Six luteal-phase sheep were used as a control during the period corresponding to the first month of pregnancy. The highest AP concentration was noted in the 5th month of pregnancy compared to these in the 1st and 2nd months (P < 0.01–P < 0.001). A decrease in the CSF AP level occurred in the 1st month of lactation compared to the concentration noted before delivery (P < 0.05). The CSF CRH concentration reached the highest level in the 4th month of pregnancy compared to these in the 1st and 2nd months (P < 0.001). A decrease in the CRH concentration was observed in the 5th month (P < 0.001, vs 4th month) and then in the 1st month of lactation (P < 0.01–P < 0.001, vs other months of pregnancy). A correlation between the CSF AP and CRH concentrations during four months of pregnancy indicated a very strong relationship (r = =0.9946), but it weakened in the 5th month (r = =0.7079). Both plasma ACTH and cortisol concentrations increased from the 1st to the 4th month of pregnancy (P < 0.01–P < 0.001) and then decreased in the 5th month (P < 0.001). The concentrations of these two hormones remained at lowered levels during early lactation. The CSF CRH, as well as plasma ACTH and cortisol levels in control non-pregnant sheep were generally lower (P < 0.001) than the ones noted in mid-pregnancy. In conclusion, the increasing secretory activity of the HPA axis in pregnant sheep is accompanied by an increase in the CSF AP concentration. The protective effect of AP from excess glucocorticoids may be seen during late pregnancy and early lactation.