Regulation of HSP90 and corticosteroid receptor mRNA by corticosterone levels in vivo.
The non-activated 9S forms of several steroid hormone receptors are heterooligomeric complexes consisting of the aporeceptor and three heat shock proteins, hsp90, hsp70 and hsp56. Hsp90 appears to play a facilitatory role in high-affinity steroid binding and to promote the efficacy of steroid actions on target tissues. Circulating glucocorticoid levels have a major regulatory impact on the binding capacity of hippocampal and hypothalamic corticosteroid receptors, a phenomenon that affects the activity of the hypothalamic-pituitary-adrenal axis and neuronal excitability in general. This study demonstrates that hsp90 mRNA is present in substantial amounts in hippocampal and hypothalamic areas characterized by high densities of corticosteroid receptors, and in the thymus. Steady-state levels of hsp90 mRNA in these regions were altered by chronic changes of circulating glucocorticoid concentrations in a site-specific fashion. In the hippocampus, mRNAs coding for hsp90 and both types of corticosteroid receptors (type I, MR and type II, GR) displayed a coordinate increase following adrenalectomy and castration (ADX/GX); in the hypothalamus only hsp90 mRNA levels were elevated, and none of the parameters studied was affected in the thymus by steroid hormone deprivation. Supplementation of ADX/GX rats with various doses of corticosterone in vivo elicited differential responses. Moderate elevation of circulating corticosterone levels normalized ADX/GX-increased hsp90 mRNA concentrations in the hippocampus and the hypothalamic paraventricular nucleus (PVN); this was associated with similar changes in GR and MR mRNA levels in the hippocampus, while GR mRNA concentrations in the PVN were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Patchev
V K
VK
Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, MD 20892.
Brady
L S
LS
Karl
M
M
Chrousos
G P
GP
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009919:Orchiectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000235:genetics*; D013950:Thymus Gland / Q000378:metabolism
D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D011987:Receptors, Steroid; D003345:Corticosterone