Progesterone regulation of catecholamine secretion from chromaffin cells.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-0622, USA. siobhana@umich.edu

Brain research 2005 May 10

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Stress stimulates the adrenal medulla to rapidly secrete catecholamines (CAs), and the adrenal cortex to release progesterone (PROG), which may locally regulate stress-induced CA release. We used bovine chromaffin cells to investigate the effects of PROG on CA secretion. PROG dose-dependently inhibited CA secretion induced by nicotinic acetylcholine receptor (nAChR) agonist 1,1-dimethyl-4-phenlypiperazinium iodide (DMPP) up to 77%. Pre-incubation with PROG up to 1 h increased this inhibition. 3alpha,5alpha-Tetrahydroprogesterone (3alpha,5alpha-THP) and dexamethasone were less potent inhibitors. Patch-clamp techniques revealed that PROG co-applied with DMPP inhibited peak DMPP-induced current up to 68% and with 3 min pre-incubation inhibited both peak and integrated current up to approximately 95%. Monitoring of FURA-2 showed that PROG similarly inhibited parallel changes in intracellular-free Ca(++) concentration. PROG also inhibited CA secretion elicited by elevated K(+) (38%), and, in single cells, suppressed Ca(++) current evoked by step depolarization, inhibiting amplitude by 15%, and reducing the time constant of current decay during depolarization by 57%. In contrast to the immediate inhibition of nicotinic current, inhibition of Ca(++) current became statistically significant only after 1 min exposure to PROG. PROG did not inhibit secretion stimulated by high Ca(++) perfusion of permeabilized cells. These data suggest that PROG inhibits CA secretion from chromaffin cells predominantly by rapidly inhibiting nAChRs, and by gradually enhancing the inactivation of voltage-dependent Ca(++) channels (VDCCs), but not by affecting secretory processes downstream of Ca(++) influx. This study supports a role for adrenocortical PROG in the regulation of CA secretion during stress.

Citation

Siobhan M Armstrong, Edward L Stuenkel. Progesterone regulation of catecholamine secretion from chromaffin cells. Brain research. 2005 May 10;1043(1-2):76-86