Regulation of Oxytocin Gene Expression and Forms of Oxytocin in the Brain

Burbach, J. Peter H.; Adan, Roger A.H.; Bree, F.M. de

doi:10.1111/j.1749-6632.1992.tb34341.x

Cited by 22 publications

(9 citation statements)

References 31 publications

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“…Unlike progesterone treatment these increased mRNA levels following oestrogen treatment are paralleled by an increased responsiveness of oxytocin release in the ventromedial nucleus following vaginocervical stimulation (14). The mechanisms by which oestrogen is responsible for modulating oxytocin-mRNA levels in the sheep brain remains unclear, however the absence of oestrogen receptors and the probable absence of a functional oestrogen responsive element in the ovine-NP1 gene (35), make it highly unlikely that this modulation of the ovine-oxytocin-NPI ' levels is a direct response and that the increase in oxytocin-gene expression is probably due to an indirect action of the steroid. Attempts to demonstrate changes in oxytocin mRNA in relation to oestrogen in the rat have not been very successful (19,20) even though there is an oestrogen responsive element which in vitro experiments with transfected cells (24,25) have shown does confer some oestrogen sensitivity to transcription of the oxytocin gene.…”

Section: Discussionmentioning

confidence: 98%

Changes in Oxytocin Immunoreactivity and mRNA Expression in the Sheep Brain during Pregnancy, Parturition and Lactation and in Response to Oestrogen and Progesterone

Broad

Kendrick

Sirinathsinghji

et al. 1993

J Neuroendocrinology

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The effects of pregnancy, parturition and lactation and exogenous treatments with oestradiol and progesterone on oxytocin (OXY) immunoreactivity and gene expression in the sheep brain were investigated. Immunocytochemistry was used to demonstrate that increased OXY-immunoreactivity occurred in cells of the paraventricular (PVN) and supraoptic nuclei (SON), the bed nucleus of the stria terminalis (BNST), the anterior commissural nuclei (ACN) and the periventricular part of the medial preoptic area (PvMP). Oxytocin immunoreactive terminals were also seen in the accessory olfactory nucleus, the glomerular and peri-glomerular layers of the olfactory bulb, the lateral septum, the zona incerta and the pars compacta of the substantia nigra. Compared to ovariectomized and late pregnant animals, the intensity of immunoreactivity was increased in all of these oxytocinergic elements at parturition, during lactation and following exogenous treatment with oestradiol. The OXY-immunoreactivity was also more intense in late pregnant animals compared to ovariectomized ones. Quantitative in situ hybridization histochemistry showed that cells in the PVN, SON, BNST and PvMP all showed significantly increased expression of OXY mRNA in animals at parturition and during lactation compared to late pregnant or ovariectomized animals. Expression levels in late pregnant animals were also significantly higher than in ovariectomized ones. Progesterone treatment significantly increased OXY mRNA in the PVN, SON, BNST and PvMP whereas oestradiol treatment was only effective in the PVN, BNST and PvMP. Combined treatment with these steroids did not significantly increase OXY mRNA levels in comparison with their administration alone. These results show that OXY-immunoreactivity and mRNA expression are at their highest in the sheep brain when maternal behaviour is induced. The increased synthesis/storage of the peptide at parturition may be due to changes in circulating concentrations of both progesterone and oestradiol during late pregnancy.

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Section: Discussionmentioning

confidence: 98%

Changes in Oxytocin Immunoreactivity and mRNA Expression in the Sheep Brain during Pregnancy, Parturition and Lactation and in Response to Oestrogen and Progesterone

Broad

Kendrick

Sirinathsinghji

et al. 1993

J Neuroendocrinology

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“…Since projections from the parvocellular region of the PVN to various brain regions within the central nervous system (CNS) are strongly implicated in maternal behavior and aggression (Bale et al, 2001;Ingram and Moos, 1992;Numan and Corodimas, 1985;Pedersen, 1997), disruption of OT production in the PVN could play an important role in cocaine's effects on other OT system dynamics (levels or release). Production of OT, largely restricted to the PVN and supraoptic nucleus (SON) (Burbach et al, 1992;Numan and Insel, 2003;Van Tol et al, 1988;Zingg and Lefebvre, 1988), has not been previously investigated in a rodent model of gestational cocaine treatment.…”

Section: Introductionmentioning

confidence: 99%

Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams

et al. 2006

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Gestational cocaine treatment in rat dams results in decreased oxytocin (OT) levels, up-regulated oxytocin receptor (OTR) binding density and decreased receptor affinity in the whole amygdala, all concomitant with a significant increase in maternal aggression on postpartum day six. Rat dams with no gestational drug treatment that received an infusion of an OT antagonist directly into the central nucleus of the amygdala (CeA) exhibited similarly high levels of maternal aggression towards intruders. Additionally, studies indicate that decreased OT release from the hypothalamic division of the paraventricular nucleus (PVN) is coincident with heightened maternal aggression in rats. Thus, it appears that cocaine-induced alterations in OT system dynamics (levels, receptors, production, and/or release) may mediate heightened maternal aggression following cocaine treatment, but the exact mechanisms through which cocaine impacts the OT system have not yet been determined. Based on previous studies, we hypothesized that two likely mechanisms of cocaine's action would be, increased OTR binding specifically in the CeA, and decreased OT mRNA production in the PVN. Autoradiography and in situ hybridization assays were performed on targeted nuclei in brain regions of rat dams on postpartum day six, following gestational treatment twice daily with cocaine (15 mg/kg) or normal saline (1 ml/kg). We now report cocaine-induced reductions in OTR binding density in the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST), but not the CeA. There was no significant change in OT mRNA production in the PVN following cocaine treatment.

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Section: In Behavioursmentioning

confidence: 99%

“…opioids, neurotransmitters, products of the gonads and thyroid) act via receptors on oxytocin-containing neurones. Only some neurones possess the receptors and thus there is a selectivity of oxytocin activation at the transcriptional level (Table 1, A) (15,16). Further control might be exacted in post-transcriptional processing in the production of polyA tail size of oxytocin mRNA, which correlates to oxytocin mRNA accumulation (Table 1, B) (17).…”

Section: The Brainmentioning

confidence: 99%

“…COOH-terminal extended forms, N-alpha acetyl oxytocin, and oxytocin metabolites, and these different forms of oxytocin can have specific roles (Table 1, K), particularly in the context of behavioural functioning (15). The enzymes which catalyse the formation of the forms may contribute to modulation of biological activities (15). One form (a little larger than native oxytocin) is induced by oestrogen and detected in the peripheral circulation and observed in patients with end-stage renal failure, suggesting one reason for its detection might be related to lowered clearance (94).…”

Section: In Behavioursmentioning

confidence: 99%

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