Comparison of the Temporal Programs Regulating Tyrosine Hydroxylase and Enkephalin Expressions in TIDA Neurons of Lactating Rats Following Pup Removal and then Pup Return

Abstract

Dopamine (DA) and enkephalin (ENK) release from the tuberoinfundibular dopaminergic neurons (TIDA) into the hypophysial portal circulation is fundamentally different under non-lactating and lactating conditions. The aim of this experiment was to compare the effect of a brief interruption then resumption of suckling on the temporal program of tyrosine hydroxylase (TH; rate-limiting enzyme of dopamine synthesis) and ENK regulation in dams. On post partum day 10, pups were removed for a 4-h period from a group of the dams then returned for 4-and 24-h periods. It was examined whether such a brief interruption of suckling provokes full up-regulation of TH and down-regulation of ENK, and whether reinitiation of suckling limits the extent to which TH upand ENK down-regulate. At the end of experiment, the animals were decapitated. In situ hybridization was used to examine the expression of TH and ENK mRNA in the arcuate nucleus where TIDA neurons reside. The results showed that, on one hand, the removal of pups induced TH up-regulation, on the other hand, ENK expression also increased 8 h after removal of pups and then started to slowly decline. In dams whose sucklings were reinitiated both TH and ENK mRNAs were up-regulated at least for a day. ENK expression responded more slowly to the removal of pups than expression of TH, and after reinitiation of suckling, the temporal program of regulation of both TH and ENK expressions ran parallel in the first 24 h.

Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons

“…Lactation was associated with a decrease in Th mRNA and an increase in Penk mRNA within the arcuate nucleus. The observation that these changes were already present in late pregnancy suggests they result from hormonal as well as suckling-induced neuronal signaling to the TIDA neurons (Berghorn et al, 2001;Szabó et al, 2011;Wang et al, 1993). The absence of a corresponding reduction in the level of TH protein indicates the complex nature of TH regulation (Kumer and Vrana, 1996) but is consistent with previous findings showing that reduced dopamine synthesis in this region results from lower levels of the activated TH (serine-40 phosphorylated) rather than total enzyme (Romanò et al, 2013).…”

“…For example, central administration of prolactin to nonpregnant female rats increases activity of tyrosine hydroxylase (TH), the rate-limiting step in dopamine synthesis, in the median eminence in non-pregnant rats but has no effect during lactation (Arbogast and Voogt, 1996;Demarest et al, 1983). Similarly, despite elevated prolactin levels during lactation, the rat arcuate nucleus shows reduced levels of both TH mRNA and TH protein, with an associated reduction in dopamine turnover and secretion at the median eminence (Andrews, 2005;Szabó et al, 2011). This downregulation of prolactin-induced dopamine synthesis and secretion during lactation does not arise from a reduction in prolactin receptor expression, with in situ hybridization revealing similar levels of prolactin receptor mRNA in the arcuate nucleus of non-pregnant and lactating rats and mice (Augustine et al, 2003;Brown et al, 2011;Kokay and Grattan, 2005).…”

60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis

“…2008 ). At the same time as the loss of dopamine secretion, there is an increase in met-enkephalin expression in the dopamine neurons ( Merchenthaler 1993 , 1994 , Szabo et al . 2011 ), and it seems possible that elevated prolactin may drive this met-enkephalin expression ( Nahi & Arbogast 2003 ).…”

“…2001 ). Recent evidence suggests that there is a direct pathway from the subparafascicular nucleus and posterior thalamus to the ventrolateral arcuate nucleus, possibly connecting with the dynorphin neurons located in this region ( Szabo et al . 2011 ).…”

Hypothalamic Control of Prolactin Secretion, and the Multiple Reproductive Functions of Prolactin

“…92 Downstream of the prolactin receptor, however, there is a change in the cellular response. 108,109,180 There is an increase in enkephalin expression in the NEDA neurons, 212,377,378 and it seems likely that elevated prolactin drives this enkephalin expression. 92 Prolactin-induced activation of the transcription factor, STAT5b, which is essential for prolactin-mediated stimulation of dopamine synthesis and release, 106 is suppressed (but not abolished) during lactation, likely mediated by an upregulation of a family of endogenous inhibitors of STAT signaling, the SOCS proteins.…”