[en] Psychosocial stress disrupts reproduction and interferes with pulsatile LH secretion. The posterodorsal medial amygdala (MePD) is an upstream modulator of the reproductive axis and stress. Corticotropin-releasing factor type 2 receptors (CRFR2s) are activated in the presence of psychosocial stress together with increased expression of the CRFR2 ligand Urocortin3 (Ucn3) in the MePD of rodents. We investigate whether Ucn3 signalling in the MePD is involved in mediating the suppressive effect of psychosocial stress on LH pulsatility. First, we administered Ucn3 into the MePD and monitored the effect on LH pulses in ovariectomized mice. Next, we delivered Astressin2B, a selective CRFR2 antagonist, intra-MePD in the presence of predator odor, 2,4,5-trimethylthiazole (TMT) and examined the effect on LH pulses. Subsequently, we virally infected Ucn3-cre-tdTomato mice with inhibitory designer receptor exclusively activated by designer drugs (DREADDs) targeting MePD Ucn3 neurons while exposing mice to TMT or restraint stress and examined the effect on LH pulsatility as well as corticosterone release. Administration of Ucn3 into the MePD dose-dependently inhibited LH pulses and administration of Astressin2B blocked the suppressive effect of TMT on LH pulsatility. Additionally, DREADDs inhibition of MePD Ucn3 neurons blocked TMT and restraint stress-induced inhibition of LH pulses and corticosterone release. These results demonstrate for the first time that Ucn3 neurons in the MePD mediate psychosocial stress-induced suppression of the GnRH pulse generator and corticosterone secretion. Ucn3 signalling in the MePD plays a role in modulating the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes, and this brain locus may represent a nodal center in the interaction between the reproductive and stress axes.
Ivanova, Deyana ; Department of Women and Children's Health, Faculty of Life Science and Medicine, King's College, London SE1 1UL, UK
Li, Xiao-Feng; Department of Women and Children's Health, Faculty of Life Science and Medicine, King's College, London SE1 1UL, UK
Mcintyre, Caitlin ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau ; Department of Women and Children's Health, Faculty of Life Science and Medicine, King's College, London SE1 1UL, UK
Liu, Yali; Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People's Republic of China
Kong, Lingsi; Department of Women and Children's Health, Faculty of Life Science and Medicine, King's College, London SE1 1UL, UK
O'Byrne, Kevin T ; Department of Women and Children's Health, Faculty of Life Science and Medicine, King's College, London SE1 1UL, UK
Language :
English
Title :
Urocortin3 in the Posterodorsal Medial Amygdala Mediates Stress-induced Suppression of LH Pulsatility in Female Mice.
BBSRC - Biotechnology and Biological Sciences Research Council MRC - Medical Research Council
Funding text :
The authors gratefully acknowledge the financial support from UKRI: Biotechnology and Biological Sciences Research Council (BBSRC) (BB/S000550/1) and Medical Research Council (MRC) (MR/N022637/1). D.I. is a doctoral student funded by an MRC-DTP studentship at King’s College London.
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