Short-Term Adrenalectomy Increases Glucocorticoid and Mineralocorticoid Receptor mRNA in Selective Areas of the Developing Hippocampus

Abstract

In the central nervous system, adrenal steroids bind to two different types of corticosteroid receptors: glucocorticoid (GR) or mineralocorticoid (MR). In vitro biochemical and autoradiographic techniques have been used to infer GR and MR protein abundance in the hippocampus. Adrenalectomy (ADX) is routinely performed to measure the normal receptor number in absence of corticosterone (B), which would otherwise interfere with the binding reaction, The developing rodent has low basal B levels until the third week of life. We were interested in whether removal of circulating B may have a greater impact in the developing hippocampus than in the adult animal. In this study we examined the effect of a 14-h ADX on hippocampal GR and MR binding capacity (Bmax) by standard binding techniques and on gene expression by in situ hybridization. ADX was performed on Day 6, 10, 14, 18, 22, 28, 35, and 45 and on adult animals. GR Bmax increased from Day 6 to adult levels by Day 22 (d6 = 159.0 +/- 27; d22 = 369.1 +/- 43; A = 344.8 +/- 23, fmol/mg protein +/- SE). In contrast, MR Bmax had adult levels on Day 6 and increased above these until Day 45, when it decreased and approached adult concentrations (d6 = 83.2 +/- 22; d45 = 123 +/- 23; A = 76.9 +/- 13, fmol/mg protein +/- SE). The greatest absolute increase for both receptors occurred between Days 22 and 45 and correlated with increases in GR and MR gene expression. Moreover, age- and region-specific changes were evident in the developing hippocampus. In addition, the adult animal also exhibited an MR mRNA upregulation after 14 h of adrenalectomy. We propose extreme caution when interpreting GR and MR Bmax values obtained after short-term adrenalectomy in both adult and developing animals since upregulation of these genes is evident in this short time frame.