Histamine inhibits adrenocortical cell proliferation but does not affect steroidogenesis

Abstract

Histamine (HA) is a neurotransmitter synthesized in most mammalian tissues exclusively by histidine decarboxylase enzyme. Among the plethora of actions mediated by HA, the modulatory effects on steroidogenesis and proliferation in Leydig cells (LCs) have been described recently. To determine whether the effects on LCs reported could be extrapolated to all steroidogenic systems, in this study, we assessed the effect of this amine on adrenal proliferation and steroidogenesis, using two adrenocortical cell lines as experimental models, murine Y1 cells and human NCI-H295R cells. Even when steroidogenesis was not modified by HA in adrenocortical cells, the biogenic amine inhibited the proliferation of H295R cells. This action was mediated by the activation of HRH1 subtype and an increase in the production of inositol phosphates as second messengers, causing cell-cycle arrest in the G2/M phase. These results indicate a new role for HA in the proliferation of human adrenocortical cells that could contribute to a better understanding of tumor pathology as well as to the development of new therapeutic agents.

Temporal and spatial distribution of mast cells and steroidogenic enzymes in the human fetal adrenal

“…Hinson et al have reported that histamine, which is one the main mediators released by mast cells, is able to activate steroid secretion in rat by acting directly on adrenocortical cells and indirectly by increasing adrenal blood flow (Hinson et al, 1991). However, previous studies had shown that histamine has no influence on aldosterone and cortisol secretion by human adult adrenal gland (Ors o et al, 1995;Pagotto et al, 2014). Conversely, involvement of 5-HT in the paracrine control of fetal adrenal cells by mast cells appears more probable.…”

H4 histamine receptors inhibit steroidogenesis and proliferation in Leydig cells

“…However, the inhibitory effect of HRH4 activation on gonadotropinstimulated steroid synthesis appears to be steroidogenic tissue-specific, considering the most recent publication of our group, which describes the lack of effect of VUF on steroidogenesis in two adrenocortical cell lines: murine Y1 cells and human NCI-H295R cells (Pagotto et al 2014). Accordingly, in those cells HA did not modify basal or adrenocorticotropic hormone-induced steroid synthesis, although it did inhibit NCI-H295R cell proliferation via HRH1 (Pagotto et al 2014). In view of these facts and previous studies by our group and others, it seems clear that research results regarding histaminergic regulation of Leydig cell function cannot be directly extrapolated to adrenocortical cells.…”

Role of Mast Cells in the Control of Aldosterone Secretion

“…Although expression of histamine type 1 receptor has been detected in the human zona glomerulosa [42], there is no clear evidence for a direct control of histamine on steroidogenesis. Indeed, some contradictory data reported that histamine augment, inhibit or do not affect aldosterone synthesis in rat, bovine or human [25,30,43,44]. The effect of heparin on the mineralocorticoid production is poorly documented in the literature.…”