Cerebellin and des-cerebellin exert ACTH-like effects on corticosterone secretion and the intracellular signaling pathway gene expression in cultured rat adrenocortical cells - DNA microarray and QPCR studies

Abstract

Abstract. Precerebellins (Cbln) belong to the C1q/TNF superfamily of secreted proteins which have diverse functions. They are abundantly expressed in the cerebellum, however, three of them are also expressed in the rat adrenal gland. All members of the Cbln family form homomeric and heteromeric complexes with each other in vitro and it was suggested that such complexes play a crucial role in normal development of the cerebellum. The aim of our study was to investigate whether Cbln1-derived peptides, cerebellin (CER) and des-Ser 1 -cerebellin (desCER) are involved in regulating biological functions of rat adrenocortical cells. In the primary culture of rat adrenocortical cells, 24 h exposure to CER or desCER notably stimulated corticosterone output and inhibited proliferative activity and similar effects were evoked by ACTH. To study gene transcript regulation by CER, desCER and ACTH, we applied Oligo GEArray ® DNA Microarray: Rat Signal Transduction Pathway Finder™. In relation to the control culture, 13 of the 113 transcripts present on the array were differentially expressed. These transcripts were either up-or down-regulated by ACTH and/or CER or desCER treatment. Validation of DNA Microarray data by QPCR revealed that only 5 of 13 genes studied were differentially expressed. Of those genes, Fos and Icam1 were up-regulated and Egr1 was down-regulated by ACTH, CER and desCER. The remaining two genes, Fasn (insulin signaling pathway) and Hspb1 (HSP27) (stress signaling pathway), were regulated only by CER and desCER, but not by ACTH. Thus, both CER and desCER have effects similar to and different from corticotrophin on the intracellular signaling pathway gene expression in cultured rat adrenocortical cells.

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

“…Rat primary adrenocortical cell culture. Method of culturing rat adrenocortical cells was described earlier [34][35][36]. Briefly, adrenals were obtained from 40, 20-22-day-old male rats.…”

Serum amphiregulin and cerebellin 1 levels in primary hypertension patients

“…Investigations about the effects of cerebellin on circulation are very limited. Rucinski et al demonstrated that cerebellin-derived peptides have adrenocorticotropic hormone (ACTH)-like effects on corticosterone output and proliferative activity of cultured rat adrenocortical cells [28]. Previous studies showed that cerebellin is a potent stimulator of direct norepinephrine release by rat adrenal medulla and enhances adrenocortical steroid secretion.…”