The interplay between oxytocin and the CRF system: regulation of the stress response

Abstract

Oxytocin (OT) has drawn the attention of researchers since 1930. Since then, many aspects of oxytocin have been uncovered, such as reproductive functions, dampening anxiety, enhancing socioemotional behavior, or regulating genomic effects on a cellular level. Here, we want to focus on the interaction between the OT system and the stress/corticotropin-releasing factor (CRF)-system of the brain. Depending on the nature of the stressor, OT is released simultaneously or directly after the stress from the neurohypophysis into the periphery and/or via somato-dendritic release in stress-sensitive brain areas. This stress-induced OT release might serve to modulate or dampen the stress response; however, the functional relevance is not yet fully understood. In this review, we will describe the effects of OT and discuss the interplay between OT and CRF on a cellular, physiological, and behavioral level.

Endogenous oxytocin inhibits hypothalamic corticotrophin‐releasing hormone neurones following acute hypernatraemia

“…As noted in the Introduction, significant prior evidence indicates that a variety of acute psychological stressors promote central oxytocin release, and substantial additional data indicates that centrally acting oxytocin can modulate stress‐induced activation of the HPA axis . In most prior studies, a specific mechanism for Oxtr‐dependent modulation of stress‐induced activation of the HPA axis is not directly revealed, although several lines of evidence have promoted the idea that, either directly or indirectly, decreased synthesis of CRH in PVN CRH neurones is involved . In considering our data in light of these studies, it is important to emphasise that acute hypernatraemia is a peripheral non‐psychological stressor that is likely to have very different effects on PVN activity than the psychological stressors previously used to promote central oxytocin release.…”

“…[6][7][8] In most prior studies, a specific mechanism for Oxtr-dependent modulation of stress-induced activation of the HPA axis is not directly revealed, although several lines of evidence have promoted the idea that, either directly or indirectly, decreased synthesis of CRH in PVN CRH neurones is involved. 9,12,13 In considering our data in light of these studies, it is important to emphasise that acute hypernatraemia is a peripheral non-psychological stressor that is likely to have very different effects on PVN activity than the psychological stressors previously used to promote central oxytocin release. Indeed, we would hypothesise that hypernatraemia is likely to evoke central oxytocin release either via direct osmotic regulation of PVN magnocellular oxytocinergic neurones, or via excitatory input from osmosensitive neurones in circumventricular organs.…”

“…10,11 Collectively, these data suggest that oxytocin release, produced in response to psychological stressors, initiates a negative-feedback mechanism that ultimately dampens stress responsiveness in part through down-regulation of CRH synthesis in the PVN. 12,13 Intriguingly, several findings from our group suggest that oxytocin release, produced by a stressor that is not associated with robust activation of the HPA axis, likely also dampens stress responsiveness, although through a mechanism not likely to involve genomic modulation of CRH synthesis. Specifically, we have reported that acute hypernatraemia, a peripheral stressor that promotes vasopressin-dependent antidiuresis and oxytocin-dependent natriuresis, [14][15][16][17] also directly reduces HPA axis activation produced by subsequent restraint stress.…”

“…Similarly, oxytocin knockout (KO) mice produce elevated levels of CRH mRNA in the PVN in response to restraint stress, whereas lactating rodents demonstrate both elevated levels of oxytocin release and reduced levels of CRH mRNA in the PVN . Collectively, these data suggest that oxytocin release, produced in response to psychological stressors, initiates a negative‐feedback mechanism that ultimately dampens stress responsiveness in part through down‐regulation of CRH synthesis in the PVN …”

Role of oxytocin in the control of stress and food intake

“…The paraventricular oxytocin receptor is also involved in social buffering actions. 89 On the other hand, it has been reported that there is no mRNA expression of the oxytocin receptor in parvocellular hypothalamic CRH-positive neurones of rats 90,91 and in hypothalamic CRH neurones of mice, 92 and oxytocin has been shown to reduce the frequency of the spontaneous excitatory postsynaptic current in some CRH neurones of mice. 61 Activation of GABAergic neurones has been shown to be involved in the inhibitory actions of oxytocin on anxiety-related behaviour and the hypothalamic-pituitary-adrenal axis.…”