Influence of 17-α-Estradiol On Catecholamine Secretion from the Perfused Rat Adrenal Gland

Abstract

Objectives:It has been known that adrenal corticosteroids influence the expression of adrenomedullary catecholamine-synthetizing enzymes and also suppress the emission of axonal-like processes in cultured chromaffin cells. In the present study, it was attempted to investigate the effect of 17-α-estradiol on catecholamine (CA) secretion evoked by acetylcholine(ACh), DMPP, McN-A-343. excess K+ and Bay-K-8644 from the isolated perfused rat adrenal gland.Methods:Mature male Sprague-Dawley rats were anesthetized with ether. The adrenal gland was isolated by the method of WaKade. A cannula used for perfusion of the adrenal gland was inserted Into the distal end of the renal vein. The adrenal gland, along with ligated blood vessels and the cannula, was carefully removed from the animal and placed on a platform of a leucite chamber.Results:The perfusion of 17-α-estradiol (1–100 uM) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.32 mM). DMPP (100 uM for 2 min). McN-A-343 (100 uM for 2 min) and Bay-K-8644 (10 uM for 4 min). while it did not affect the CA secretory effect of high K+ (56 mM), Also, in the presence of 17-β-estradiol, CA secretion of ACh, DMPP and McN-A-343, without any effect on excess K+-evoked CA sectretion was depressed. However, in adrenal glands pre-loaded with 17-α-estradiol (10 uM) plus tamoxifen (2 uM). which is known to be a selective antagonist of estrogen receptors (for 20 min), CA secretory responses evoked by ACh, DMPP and McN-A-343 were considerably recovered as compared to that of 17-α-estradiol only, but excess K+-induced CA secretion was not affected. However, pre-treatment with 17-α-estradiol in the presence of meclopramide(dopaminergic antagonist) did not affect the secretory effect of CA evoked by ACh, DMPP, McN-A-343 and high potassium.Conclusions:These results suggest that 17-α-estradiol causes the marked inhibition of CA secretion evoked by cholinergic receptor stimulation, but not that by excess K+, indicating strongly that this effect may be mediated by inhibiting the influx of extracellular calcium into the rat adrenomedullary chromaffin cells through the activation of inhibitory estrogen receptors, and it also plays a modulatory role in regulating CA secretion.

Nongenomic Regulation of the Kinetics of Exocytosis by Estrogens

“…Our results on perfused rat adrenal gland confirm and extend previous results, which showed that acute application of estrogens caused the inhibition of secretory responses in chromaffin tissues when they were applied at micromolar concentrations (López et al, 1991;Park et al, 1996;Dar and Zinder, 1997). Although the current study was not conducted to examine the target of estrogens to inhibit secretion, it seems that they affected the electrical properties of cell membrane.…”

“…The naturally occurring steroid 17␤-estradiol, its ␣-isomer, and other molecules with estrogen activity have been widely studied in a variety of tissues including chromaffin cells (López et al, 1991;Park et al, 1996;Dar and Zinder, 1997) and PC-12 cells (Chen et al, 1998;Kim et al, 2000; for a recent review, see Falkenstein et al, 2000b).…”

Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases

“…In 1991, Lopez et al [ 149 ] reported the potential role of Es in decreasing the secretion of catecholamines from the adrenal chromaffin cells, which represent an essential source of total plasma catecholamines [ 21 ]. These data were also corroborated by Park et al [ 150 ], who showed how Es administration to the rats’ adrenal glands caused a marked inhibition of catecholamine secretion evoked by cholinergic receptor stimulation. In line with these reports, Gomes and colleagues [ 151 ] observed that, consequent to ovariectomy (OVX), female rats displayed increased plasma catecholamine levels than male rats following gonadectomy.…”

Modulation of hypoglycemia‐induced increases in plasma epinephrine by estrogen in the female rat

“…Several in vitro studies have demonstrated that relatively high concentrations of estrogen can acutely and therefore presumably nongenomically modulate adrenal medullary function. For example, nicotinic agonist‐induced catecholamine secretion is suppressed within minutes of exposure to estradiol in the isolated perfused rat and feline adrenal gland (Lopez et al,1991; Park et al,1996). In addition, Kim et al (2000) have demonstrated that short‐term exposure to 17β‐estradiol suppresses KCl‐induced [ 3 H] norepinephrine secretion and agonist‐induced intracellular Ca 2+ transients in the PC‐12 cell line, an established model of the medullary chromaffin cell.…”