PMID- 34428676 OWN - NLM STAT- MEDLINE DCOM- 20210915 LR - 20210915 IS - 1879-3231 (Electronic) IS - 0093-691X (Linking) VI - 174 DP - 2021 Oct 15 TI - Involvement of neurosteroids in the control of hypothalamic-pituitary-adrenal axis activity in pregnant sheep under basal and stressful conditions. PG - 114-120 LID - S0093-691X(21)00299-5 [pii] LID - 10.1016/j.theriogenology.2021.08.026 [doi] AB - 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 mug/240 muL/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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Misztal, Tomasz AU - Misztal T AD - Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St, 05-110, Jablonna, Poland. Electronic address: t.misztal@ifzz.pl. FAU - Mlotkowska, Patrycja AU - Mlotkowska P AD - Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St, 05-110, Jablonna, Poland. FAU - Marciniak, Elzbieta AU - Marciniak E AD - Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St, 05-110, Jablonna, Poland. FAU - Roszkowicz-Ostrowska, Katarzyna AU - Roszkowicz-Ostrowska K AD - Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St, 05-110, Jablonna, Poland. FAU - Misztal, Anna AU - Misztal A AD - Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3 St, 05-110, Jablonna, Poland. LA - eng PT - Journal Article DEP - 20210820 PL - United States TA - Theriogenology JT - Theriogenology JID - 0421510 RN - 0 (Neurosteroids) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Adrenocorticotropic Hormone/metabolism MH - Animals MH - Corticotropin-Releasing Hormone/metabolism MH - Female MH - Hydrocortisone MH - *Hypothalamo-Hypophyseal System/metabolism MH - *Neurosteroids MH - Pituitary-Adrenal System MH - Pregnancy MH - Sheep OTO - NOTNLM OT - Allopregnanolone OT - Finasteride OT - Neurosteroids OT - Pregnancy OT - Sheep OT - Stress response COIS- Declaration of competing interest The authors declare no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. EDAT- 2021/08/25 06:00 MHDA- 2021/09/16 06:00 CRDT- 2021/08/24 20:20 PHST- 2021/04/14 00:00 [received] PHST- 2021/08/17 00:00 [revised] PHST- 2021/08/19 00:00 [accepted] PHST- 2021/08/25 06:00 [pubmed] PHST- 2021/09/16 06:00 [medline] PHST- 2021/08/24 20:20 [entrez] AID - S0093-691X(21)00299-5 [pii] AID - 10.1016/j.theriogenology.2021.08.026 [doi] PST - ppublish SO - Theriogenology. 2021 Oct 15;174:114-120. doi: 10.1016/j.theriogenology.2021.08.026. Epub 2021 Aug 20.