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Neurosteroid regulation of oxytocin and vasopressin release from the rat supraoptic nucleus
Author(s) -
Widmer Hélène,
Ludwig Mike,
Bancel Frédéric,
Leng Gareth,
Dayanithi Govindan
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00233.x
Subject(s) - supraoptic nucleus , oxytocin , vasopressin , endocrinology , medicine , nucleus , chemistry , neuropeptide , neuroscience , biology , receptor
In adult rats somato‐dendritic release of oxytocin and vasopressin from magnocellular neurones in the supraoptic nucleus of the hypothalamus has important autoregulatory actions on the neuronal electrical activity, and in neonatal rats it plays a role in the development of dendritic arborisation. In the adult, oxytocin effects are modulated by allopregnanolone via an interaction with inhibitory GABA A receptors. This study examined the effects of allopregnanolone, progesterone and 17β‐oestradiol on oxytocin and vasopressin release from intact isolated supraoptic nuclei and from the neurophypophyses in rats of differing ages. In supraoptic nuclei from rats of 3–4 weeks old or less, all three neurosteroids induced oxytocin release from the isolated supraoptic nucleus, but only allopregnanolone induced significant release of vasopressin. Surprisingly, in these very young rats, allopregnanolone‐induced oxytocin release was inhibited by GABA A receptor antagonists as well as by an oxytocin receptor antagonist. By contrast, in supraoptic nuclei from adult rats allopregnanolone‐induced oxytocin release was much smaller, and was enhanced in the presence of bicuculline. The GABA A receptor agonist muscimol also induced oxytocin release from supraoptic nuclei in young rats, but had no effect in adult rats. Oxytocin cells isolated from young rats showed an increase in [Ca 2+ ] i in response to both allopregnanolone and muscimol. Allopregnanolone had no effect on [Ca 2+ ] i or on the release of oxytocin or vasopressin from neurohypophysial axon terminals in either young or old rats. We conclude that, in very young rats, (i) neurosteroids induce oxytocin release from the supraoptic nucleus by a mechanism that partly depends on the presence of GABA, which in young rats is depolarising to oxytocin cells, and which also partly depends upon endogenous oxytocin, and (ii) the effect of allopregnanolone upon oxytocin release changes with age, as the functional activity of GABA A receptors changes from excitation to inhibition of oxytocin cells.