Prolactin and Oxytocin Interaction in the Paraventricular and Supraoptic Nuclei: Effects on Oxytocin mRNA and Nitric Oxide Synthase

Abstract

We investigated the contribution of prolactin and oxytocin to the increase in staining for NADPH-d and oxytocin mRNA in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) observed at the end of pregnancy, or following a steroid-priming regimen that mimics the hormonal profile of late pregnant females. Ovariectomized rats received chronic implants of silastic capsules containing oestrogen and progesterone followed by progesterone removal. In experiment 1, oxytocin antagonist (OTA) was administered to rats to investigate whether intranuclear oxytocin release was necessary for NADPH-d staining. In experiments 2a and b, rats received concurrent treatment with bromocryptine (0.5 mg/day) to suppress endogenous prolactin release, and either systemic prolactin (0.5 mg once daily), or prolactin (2 micro g/ micro l), or vehicle infused twice a day into the third ventricle, or chronic oxytocin infusion (24 ng/day) for 3 days following progesterone removal. Brains were then processed for NADPH-d histochemistry. In experiment 3, the interaction of prolactin and oxytocin on oxytocin mRNA within the SON and PVN was examined. NADPH-d staining in the SON and PVN was reduced by the highest dose of the OTA, and by bromocryptine treatment. Central prolactin and oxytocin replacement completely restored NADPH-d staining in bromocryptine-treated rats. Finally, both bromocryptine and the OTA suppressed oxytocin mRNA expression and prolactin replacement restored expression levels to that of controls. Together, these data suggest that the increased capacity to produce nitric oxide in the SON and PVN during late pregnancy is dependent on prolactin stimulating oxytocin gene mRNA and hence intranuclear oxytocin release.

Rapid Eye Movement Sleep Is Reduced in Prolactin-Deficient Mice

“…PRL excites LDT neurons (Takahashi et al, 2000), and LDT neuron activation increases NO production and elevates extracellular NO (Leonard et al, 2001). PRL induces inducible NOS (iNOS) mRNA in glioma cells in vitro (Raso et al, 1999) and neuronal NOS (nNOS) protein expression in neurons in the paraventricular and supraoptic nuclei in vivo (Popeski et al, 2003). PRL receptor activation upregulates the expression of nNOS protein in GH 3 rat pituitary adenoma cells (Secondo et al, 2003).…”

Expression of the long form of the prolactin receptor in magnocellular oxytocin neurons is associated with specific prolactin regulation of oxytocin neurons

“…Intracerebroventricular administration of prolactin induces activation of c-Fos in the SON (8). Prolactin has been shown to specifically increase oxytocin mRNA expression (20,21,50) and to stimulate oxytocin secretion from hypothalamic explants (43) or into portal blood, in vivo (62). By contrast, hyperprolactinemia can also inhibit the stress-induced release of oxytocin (7).…”

Impact of gestational cocaine treatment or prenatal cocaine exposure on early postpartum oxytocin mRNA levels and receptor binding in the rat

“…A third system of oxytocin mRNA regulation is mediated through the prolactin system (Bakowska and Morrell, 1997;Ghosh and Sladek, 1995a;Ghosh and Sladek, 1995b;Popeski et al, 2003). Decreased prolactin release has been shown to reduce oxytocin mRNA production (Grattan, 2001).…”

“…During lactation, dopamine signaling, which is known to be altered by cocaine, has a direct inhibitory influence on prolactin levels (Byrnes and Bridges, 2007;Mello et al, 1994;Voogt, Lee, Yang, and Arbogast, 2001). Interestingly, acute dopamine D2 receptor activation can also reduce prolactin release, in turn reducing oxytocin mRNA production (Byrnes and Bridges, 2007;Popeski et al, 2003). Chronic cocaine administration has been associated with an overall decrease in the number of D2 receptors (Nader et al, 2006), which could then result in an overall increase in prolactin levels and thus contribute to the increase we saw in oxytocin mRNA; however, this has not been studied in a lactational model.…”

“…Considering dopamine's involvement in reward circuitry, it would be interesting to examine the oxytocin in regions associated with reward, such as the nucleus accumbens and amygdala, which are likely involved in maternal behavior. Oxytocin receptor activation may also further increase oxytocin release and possibly protein synthesis (Neumann et al, 1996), either directly through oxytocin receptor activation, or indirectly by increasing prolactin levels (Popeski et al, 2003;Samson et al, 1986) to stimulate oxytocin mRNA synthesis.…”