Glucocorticoid sensitizers Bag1 and Ppid are regulated by adolescent stress in a sex-dependent manner.
Early life stress precipitates dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and this effect is most pronounced in females. The mechanisms that mediate female sensitivity to stress-induced HPA axis dysregulation are unknown. The purpose of this study was to determine whether sex moderates the effects of chronic adolescent stress on glucocorticoid receptor (GR) translocation and moderators of the GR system. Female adolescent rats with a history of chronic stress exposure demonstrated a delayed resolution of the plasma corticosterone response to an acute stressor and this delay was accompanied by attenuated GR translocation compared to control adolescent females. The chronic stress-induced phenotype in females was similar to the baseline phenotype in male adolescent rats. Conversely, the expression patterns of GR moderators/co-chaperones became more sexually dimorphic following chronic stress, suggesting divergent function of the GR system between male and female adolescent rats. Gene expression of Ppid, a positive regulator of the GR, was predicted by plasma estradiol and 34% lower in control adolescent females than males, indicating that sex steroids may play a role in the sexually dimorphic response. After chronic adolescent stress, females displayed elevated hippocampal expression of Bag1 and Ppid genes that was not observed in males. Overall, the GR output to an acute stressor, illustrated by transcription of Nr3c1 (encoding the GR), Bag1, Fkbp5, Ppid, and Src1, was significantly upregulated and differed in a sex-specific and chronic stress-dependent manner. This study provides new evidence for sex differences during development and adaptation of the glucocorticoid receptor chaperone system.
Department of Psychiatry and Behavioral Sciences, Emory University, 101 Woodruff Circle, Suite 4000, Atlanta, GA 30322, United States.
Chase H
CH
Bourke
Madiha Q
MQ
Raees
Sanjana
S
Malviya
Cory A
CA
Bradburn
Elisabeth B
EB
Binder
Gretchen N
GN
Neigh
D000818:Animals; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D021983:Cyclophilins / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004291:Dominance-Subordination; D005260:Female; D018507:Gene Expression Regulation, Developmental; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012149:Restraint, Physical / Q000502:physiology; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D022021:Tacrolimus Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D000099159:Tacrolimus Binding Protein 5; D000097322:Peptidyl-Prolyl Isomerase D
D003345:Corticosterone; D021983:Cyclophilins; D004268:DNA-Binding Proteins; D012739:Gonadal Steroid Hormones; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099159:Tacrolimus Binding Protein 5; C091732:BCL2-associated athanogene 1 protein; C542344:NR3C1 protein, rat; C581109:Ppid protein, rat; D000097322:Peptidyl-Prolyl Isomerase D