title: 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.
authors.affiliation: Laboratory of Molecular Endocrinology and Signal Transduction, Institute of Biology and Experimental Medicine, National Research Council (IByME-CONICET), Vuelta de Obligado 2490, CP 1428 Buenos Aires, Argentina Department of Biological Chemistry, School of Sciences, University of Buenos Aires (UBA), CP 1428 Buenos Aires, Argentina.
authors.forename: Romina Maria
authors.initials: RM
authors.lastname: Pagotto
authors.forename: Elba Nora
authors.initials: EN
authors.lastname: Pereyra
authors.forename: Casandra
authors.initials: C
authors.lastname: Monzón
authors.forename: Carolina
authors.initials: C
authors.lastname: Mondillo
authors.forename: Omar Pedro
authors.initials: OP
authors.lastname: Pignataro
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D059565:G2 Phase Cell Cycle Checkpoints; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D051379:Mice; D013256:Steroids / Q000378:metabolism*
chemical_list: D013256:Steroids; D006632:Histamine
keywords: adrenocortical cells; histamine; proliferation; steroidogenesis