Endogenous Opioid Peptides Contribute to Suckling-Induced Prolactin Release by Suppressing Tyrosine Hydroxylase Activity and Messenger Ribonucleic Acid Levels in Tuberoinfundibular Dopaminergic Neurons*

Abstract

The endogenous opioid peptides have been implicated in the control of the suckling-induced PRL rise during lactation. This study examined the role of the endogenous opioid peptides in suppressing tuberoinfundibular dopaminergic neuronal activity during lactation. In the first experiment, lactating rats were constantly exposed to pups. Naloxone (NAL; 60 mg/kg x h; i.v.), an opioid receptor antagonist, or saline was infused for 12 h. Blood was collected before and at 2-h intervals during the infusion. NAL suppressed circulating PRL levels to less than 36% of control values at 4, 6, 8, and 12 h after the onset of the infusion. Tyrosine hydroxylase (TH) activity in the stalk-median eminence and TH messenger RNA signal levels in the arcuate nucleus were determined at the end of the NAL infusion. TH activity and TH messenger RNA signal levels were increased 2.5- and 2.7-fold, respectively, after the 12-h NAL infusion. Even though the time spent with their pups was similar between the two groups, the pups in the NAL-treated group failed to gain weight during the 12-h NAL infusion period, whereas the control litters (8 pups) gained 5 g. In a second experiment, pups were removed from the dams before the 12-h NAL infusion and were returned after 11 h. Blood was collected before the infusion, at 3-h intervals during the pup separation period, and at 15-min intervals after reunion with the pups. Plasma PRL in control and NAL-treated rats was low (1-15 ng/ml) and similar during the separation period. The suckling-induced PRL surge in NAL-treated rats was markedly attenuated to 9-25% of control levels (350-650 ng/ml). After a 1-h suckling episode, TH activity in the stalk-median eminence of NAL-treated rats was 4.5-fold greater than controls. Litter weight gains were significantly less in NAL-treated rats during the 1-h suckling episode. These data indicate that the endogenous opioid peptides are an integral component for increasing PRL release in response to suckling and they act to decrease tuberoinfundibular dopaminergic neuronal activity during lactation, in part, by suppressing TH gene expression.

Prolactin stimulates transepithelial calcium transport and modulates paracellular permselectivity in Caco-2 monolayer: mediation by PKC and ROCK pathways

“…In vivo studies in normal rats suggested that PRL stimulated both transcellular active and paracellular passive calcium transport in the duodenum and proximal jejunum (10,33). Exposure to high physiological levels of PRL of 400 -600 ng/ml, which are comparable to the levels attained during lactation and suckling (2), rapidly enhanced transepithelial calcium transport in isolated duodenal epithelium and intestine-like Caco-2 monolayer in a dose-dependent manner (25). However, the signaling pathways of PRL in the intestinal absorptive cells and the detailed mechanisms of the PRL-enhanced calcium transport were not completely understood.…”

Mu and kappa opioid receptor expression in the mediobasal hypothalamus and effectiveness of selective antagonists on prolactin release during lactation

“…The control of prolactin secretion during lactation also involves input from prolactin releasing factor(s) (Samson et al, 1986; Murai and Ben-Jonathan, 1987; Hyde et al, 1987; Samson et al, 1989). Other neurotransmitter systems, most notably the endogenous opioid peptides, appear to act at the central nervous system level to modulate dopamine and/or prolactin-releasing factor input to the anterior pituitary gland to control prolactin secretion (Arbogast and Voogt, 1998; Callahan et al, 2000; Ben-Jonathan and Hnasko, 2001). …”

“…Immunoneutralization of β-endorphin, dynorphin, leu-enkephalin or met-enkephalin abolishes suckling-induced prolactin release (Jaworski et al, 1997; Callahan et al, 2000). Naloxone, an opioid receptor antagonist, suppresses the suckling-induced prolactin surge after a period of pup deprivation and in a continuous suckled model (Selmanoff and Gregerson, 1986; Arbogast and Voogt, 1998). Naloxone suppression of suckling-dependent prolactin release is associated with increased tyrosine hydroxylase activity and tyrosine hydroxylase mRNA levels in TIDA neurons (Arbogast and Voogt, 1998).…”

“…Naloxone, an opioid receptor antagonist, suppresses the suckling-induced prolactin surge after a period of pup deprivation and in a continuous suckled model (Selmanoff and Gregerson, 1986; Arbogast and Voogt, 1998). Naloxone suppression of suckling-dependent prolactin release is associated with increased tyrosine hydroxylase activity and tyrosine hydroxylase mRNA levels in TIDA neurons (Arbogast and Voogt, 1998). Three major types of opioid receptors, kappa (κ), mu (μ), and delta (δ), mediate the actions of endogenous opioid peptides, dynorphin, endorphin and enkephalin (Minami and Satoh, 1995).…”

Coadministration of dextromethorphan during pregnancy and throughout lactation prevents morphine-induced hyperprolactinemia in female rats

“…Many studies have reported that these PRL nocturnal surges during early pregnancy (18,19), the antepartum PRL surge during late pregnancy (20), and suckling-induced PRL secretion during lactation (21,22) are regulated by opioids and mediated by contemporary stimulation of both kand m-opioid receptors on tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus (23). It has been found that k-opioid receptor inhibition of TIDA neuronal activity may predominate during late pregnancy (23)(24)(25).…”