Prolactin regulation of oxytocin neurone activity in pregnancy and lactation

Abstract

Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s , respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s in lactating rats but excited none in virgin or pregnant rats (χ = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect phosphorylation of extracellular regulated kinase 1 or 2, or of Akt in the supraoptic or paraventricular nuclei of virgin or lactating rats. Hence, prolactin inhibition of oxytocin neurones is lost in lactation, which might allow concurrent elevation of prolactin secretion from the pituitary gland and activation of oxytocin neurones for synthesis and delivery of milk to the newborn.

The osmoresponsiveness of oxytocin and vasopressin neurones: Mechanisms, allostasis and evolution

“…138 To accommodate these requires a resetting of these homeostatic set points, and this involves a complex array of adaptations that affect the oxytocin cells. 133,[139][140][141][142] Resetting of the set-points for volume and electrolyte balance arises in part from the actions on the subfornical organ and OVLT of relaxin, a peptide hormone produced by corpora lutea in pregnancy in increasing amounts as pregnancy progresses. Circulating relaxin stimulates both water intake 143 and vasopressin secretion via its actions on the AV3V region, and the combination of increased water intake and increased water retention contributes to a dilutional expansion of plasma volume with accompanying hyponatraemia.…”

30 years after: CNS actions of prolactin: Sources, mechanisms and physiological significance

“…There is some evidence that the short forms may act as regulatory molecules, by forming heterodimers with the long form of the receptor, and thereby blocking signal transduction, 78 although recent studies looking specifically at the functions of the short forms have begun to identify roles for these isoforms that are distinct from the long form. 87,88 Hence, the actions of PRL on behaviour might involve rapid changes in the activity of PRL-sensitive neuronal networks or slower changes in gene expression within these networks, which might have much greater long-term effects on network function. In particular, using electrophysiological recordings in tuberoinfundibular dopamine (DA) neurones, which are involved in the regulation of PRL secretion from the pituitary gland, three groups have independently characterised very rapid actions (minutes) of PRL to increase the firing rate of these neurones in mice 81,82 and rats.…”

“…86 PRL has also been shown to rapidly reduce the firing rate of oxytocin neurones, in vivo. 87,88 Hence, the actions of PRL on behaviour might involve rapid changes in the activity of PRL-sensitive neuronal networks or slower changes in gene expression within these networks, which might have much greater long-term effects on network function. As we have already alluded to, an important concept in considering the action of PRL in the brain is the fact that these actions may be induced by multiple different ligands all acting through the PRL receptor.…”

The role of prolactin in the suppression of Crh mRNA expression during pregnancy and lactation in the mouse

“…These neurones are known to express prolactin receptors and to inhibit Crh gene transcription . Although acute treatment with prolactin appears to inhibit oxytocin release, this effect is lost or even reversed during lactation . Interestingly, the secretion of oxytocin is increased following chronic treatment of nonpregnant rats with prolactin .…”

“…42 Although acute treatment with prolactin appears to inhibit oxytocin release, 41 this effect is lost or even reversed during lactation. 43 Interestingly, the secretion of oxytocin is increased following chronic treatment of nonpregnant rats with prolactin. 27 Together, these data support a mechanism by which oxytocin could mediate the suppressive action of prolactin upon the CRH neurones.…”