Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Abstract

Abstract.Previous studies have shown that proteasome inhibitors promote the accumulation of steroidogenic acute regulatory protein (StAR) in cultured rat adrenocortical cells. Unexpectedly, this response was associated with a moderate lowering in the corticosterone secretion and proliferation rate of cultured cells. Hence, we studied the effects of proteasome inhibitors MG115 and MG132 on the secretion and proliferative activity of the regenerating adrenal cortex in rats 5 days after surgery. Animals were given two subcutaneous injections of 0.15 or 1.5 nmol/100 g of inhibitors 24 and 12 h before decapitation. Real-time PCR and Western blotting showed that StAR expression, both mRNA and protein, was markedly lower in regenerating adrenals than in the intact gland of sham-operated rats. Neither MG115 nor MG132 affected StAR expression in regenerating gland. Inhibitors induced a slight decrease in the plasma concentrations of aldosterone and corticosterone, but did not significantly alter metaphase index of the regenerating adrenal cortex. Our findings provide the first evidence that down-regulation of StAR occurs during the early stages of adrenal regeneration. Moreover, this suggests that the steroidogenic pathway is more sensitive to proteasome inhibitors than that regulating proliferative activity of regenerating adrenal cortex in the rat.

Expression of selected genes involved in steroidogenesis in the course of enucleation-induced rat adrenal regeneration

“…This protein is responsible for the transport of cholesterol from the outer to the inner mitochondrial membrane. An earlier study revealed notable downregulation of both StAR gene and protein expression levels in regenerating rat adrenals on experimental day 5 (31). The current study confirmed these data and revealed a significant upregulation in gene expression between experimental days 8-15.…”

Sex-related gene expression profiles in the adrenal cortex in the mature rat: Microarray analysis with emphasis on genes involved in steroidogenesis

“…This protein is responsible for the transport of cholesterol from the outer to the inner mitochondrial membrane ( 53 ). Earlier immunohistochemical and immunofluorescence studies have revealed the presence of Star protein in both the ZG and ZF/R of the rat adrenal cortex ( 54 – 57 ). In the mouse adrenal glands, Star mRNA levels (assessed by RT-PCR) have been reported be slightly higher in males than in females, although the differences were not statistically significant ( 58 ).…”

Mitochondrial sirtuins in the rat adrenal gland: location within the glands of males and females, hormonal and developmental regulation of gene expressions

“…QPCR was performed by means of the Lightcycler 2.0 instrument (Roche) with the 4.05 software version. SYBR green detection system was applied as described earlier [30,31,[38][39][40]. Every of 20 µL reaction mixtures contained 2 µL template cDNA (standard or control), 0.5 µM of specific primer and a 3.5 µM MgCl 2 .…”