The Effect of Swelling on TRH and Oxytocin Secretion From Hypothalamic Structures

Abstract

1. Cell swelling induces exocytosis of material stored in secretory vesicles resulting in a secretory burst of peptidic hormones or enzymes from various types of cells including endocrine cells and neurons. We have previously shown that swelling-induced exocytosis possesses limited selectivity; hypotonic medium evokes TRH but not oxytocin release from hypothalamic paraventricular nucleus (PVN) and neurohypophysis (NH). 2. It is the aim of this study to ascertain whether the swelling-induced oxytocin secretion could be unmasked by the inhibition of specific osmotic response using Ca(2+)-free medium and GdCl(3), an inhibitor of stretch activated channels. 3. Oxytocin release from the PVN was stimulated by the hypotonic medium only in the presence of 50 or 100 microM GdCl(3.) Oxytocin release from supraoptic nucleus (SON) was also stimulated by the Ca(2+)-free hypotonic medium in the presence of GdCl(3). Oxytocin secretion from the NH was not stimulated even in the presence of GdCl(3), both in Ca(2+) containing and Ca(2+)-free medium. TRH response to swelling-inducing stimulus was not affected by the presence of GdCl(3). 4. An intranuclear oxytocin secretion to hyposmotic stimulation within the PVN and the SON could be unmasked by the inhibiting specific response by GdCl(3). At these conditions general secretory response to swelling-inducing stimuli emerged. Secretion of oxytocin from the NH was not affected by any of these treatments. 5. Peptides and proteins released after cell swelling can play an important role in the pathophysiology of ischemia and could be mediators of local or remote preconditioning. Disruption of mechanosensitive gating in magnocellular neurosecretory cells could result in an inadequate secretory response (e.g. stimulation instead of inhibition and vice versa) of hormones engaged in water and salt metabolism regulation.

Cell Swelling-induced Peptide Hormone Secretion

“…Under our experimental conditions, both neuropeptides are secreted into medium from the same tissue explants, though most likely from different neurons: parvocellular and magnocellular for TRH and oxytocin respectively. As expected TRH secretion was stimulated by cell swelling [29,[36][37][38]61], while oxytocin, neurohormone engaged in water and salt regulation, was not released after cell swelling-inducing stimuli; hypotonicity or ethanol in isosmotic medium [38]. This is in good agreement with observations that ethanol inhibits the release of oxytocin from the posterior pituitary induced by high K + [71] or suckling [72] and that hypotonic stimuli hyperpolarize magnocellular neurosecretory cells via stretch-inactivated channels [73].…”

“…The trivalent lanthanide GdCl 3 blocks mechanogated channels [44] and also voltage sensitive Ca 2+ channels [reviewed 45]. GdCl 3 in the culture medium does not negatively modify hyposmolarity-or ethanol-induced TRH release from isolated pancreatic islets, hypothalamic PVN or posterior pituitaries [37,38], or prolactin release from acutely dispersed anterior pituitary cells induced by hypotonicity [22,37]. From these experiments it can be concluded that signal leading to exocytosis after cell swelling does not involve GdCl 3 sensitive mechanogated channels.…”

“…Swelling-induced secretion can be induced in different parts of neurons -similar TRH release was evoked from the hypothalamic paraventricular nucleus (mostly perikarya) and the median eminence or neurohypophysis (exclusively axon terminals) [28,29,[36][37][38]. Cell swelling induced exocytosis is not restricted to endocrine cells and hormones.…”

“…Inhibition of prostaglandin biosynthesis by indomethacin (cyclooxygenase inhibitor) and that of leukotrienes by nordihydroguaiaretic acid (NDGA, lipoxygenase inhibitor) did not adversely affect hypotonicity-induced prolactin release from perifused [38]. Signal transduction leading to exocytosis after cell swelling does not involve indomethacin and NDGA sensitive mediators including prostaglandins and leukotriens.…”

“…To shed more light on the interrelations between specific and unspecific responses we studied osmotic effect on exocytosis from tissue explants of hypothalamic PVN and posterior pituitary with simultaneous thyrotropin releasing hormone (TRH) and oxytocin examination [14,37,38,61]. Under our experimental conditions, both neuropeptides are secreted into medium from the same tissue explants, though most likely from different neurons: parvocellular and magnocellular for TRH and oxytocin respectively.…”