TY - JOUR
T1 - Differential glucocorticoid effects on stress-induced gene expression in the paraventricular nucleus of the hypothalamus and ACTH secretion in the rat
AU - Pace, Thaddeus W.W.
AU - Gaylord, Reginald I.
AU - Jarvis, Erin
AU - Girotti, Milena
AU - Spencer, Robert L.
N1 - Funding Information:
We are grateful to Serge Campeau and Heidi Day for their generous assistance with the in situ hybridization procedures used for these studies. These studies were supported by NIH Grants MH-62456, MH-75968 and F31-13011.
PY - 2009
Y1 - 2009
N2 - Although previous studies have examined the extent to which adrenocorticotropic hormone (ACTH) secretion depends on endogenous glucocorticoid levels, few have examined the parallel glucocorticoid dependency of gene expression within the corticotropin releasing hormone (CRH) neuron containing subregion of the hypothalamic paraventricular nucleus (PVN). This study examined resting and stress-induced expression of three immediate early genes (c-fos, zif268, and NGFI-B mRNAs) and two phenotypic restricted immediate early genes that code for ACTH secretagogues (CRH and arginine vasopressin [AVP] hnRNAs) in the PVN of adrenalectomized (ADX) rats given either 0.9% saline to drink for 5 days or saline with corticosterone (CORT; 25 μg/ml). CORT-containing saline was replaced with saline 18 h before testing to ensure clearance of CORT at the time of testing. Dependent measures were examined 0, 15, 30, 60, or 120 min after 30 min restraint. Compared to sham surgery, ADX produced a large upregulation of basal ACTH secretion but only a trend for an increase in basal PVN CRH and parvocellular (mp) PVN AVP hnRNA expression, and a marked augmentation of restraint-induced ACTH secretion and the expression of all five genes examined. CORT containing saline partially normalized basal and restraint-induced ACTH secretion and restraint-induced AVP hnRNA, c-fos mRNA, and zif268 mRNA in the PVN in ADX rats. In contrast, expression patterns of restraint-induced PVN CRH hnRNA and NGFI-B mRNA were not different between ADX rats with or without CORT replacement. Given that there was no circulating CORT present at the time of restraint challenge in either group of ADX rats, the differential impact of CORT replacement on restraint-induced PVN gene expression must reflect differential dependency of the expression of these genes in the PVN on the prior presence of CORT.
AB - Although previous studies have examined the extent to which adrenocorticotropic hormone (ACTH) secretion depends on endogenous glucocorticoid levels, few have examined the parallel glucocorticoid dependency of gene expression within the corticotropin releasing hormone (CRH) neuron containing subregion of the hypothalamic paraventricular nucleus (PVN). This study examined resting and stress-induced expression of three immediate early genes (c-fos, zif268, and NGFI-B mRNAs) and two phenotypic restricted immediate early genes that code for ACTH secretagogues (CRH and arginine vasopressin [AVP] hnRNAs) in the PVN of adrenalectomized (ADX) rats given either 0.9% saline to drink for 5 days or saline with corticosterone (CORT; 25 μg/ml). CORT-containing saline was replaced with saline 18 h before testing to ensure clearance of CORT at the time of testing. Dependent measures were examined 0, 15, 30, 60, or 120 min after 30 min restraint. Compared to sham surgery, ADX produced a large upregulation of basal ACTH secretion but only a trend for an increase in basal PVN CRH and parvocellular (mp) PVN AVP hnRNA expression, and a marked augmentation of restraint-induced ACTH secretion and the expression of all five genes examined. CORT containing saline partially normalized basal and restraint-induced ACTH secretion and restraint-induced AVP hnRNA, c-fos mRNA, and zif268 mRNA in the PVN in ADX rats. In contrast, expression patterns of restraint-induced PVN CRH hnRNA and NGFI-B mRNA were not different between ADX rats with or without CORT replacement. Given that there was no circulating CORT present at the time of restraint challenge in either group of ADX rats, the differential impact of CORT replacement on restraint-induced PVN gene expression must reflect differential dependency of the expression of these genes in the PVN on the prior presence of CORT.
KW - AVP
KW - CRH
KW - Glucocorticoid negative feedback
KW - HPA axis
KW - Immediate early gene
KW - PVN
UR - http://www.scopus.com/inward/record.url?scp=70549102501&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70549102501&partnerID=8YFLogxK
U2 - 10.1080/10253890802530730
DO - 10.1080/10253890802530730
M3 - Article
C2 - 19065454
AN - SCOPUS:70549102501
SN - 1025-3890
VL - 12
SP - 400
EP - 411
JO - Stress
JF - Stress
IS - 5
ER -