Aims: 

Tuberoinfundibular peptide of 39 residues (TIP39), the endogenous ligand of parathyroid hormone 2 receptor (PTH2 receptor) is expressed in the posterior intralaminar complex of the thalamus (PIL), an area, through which the reflex arch of suckling has been described. In the present study, we addressed the function of TIP39 neurons in lactation.

Methods: 

In situ hybridization, immunohistochemistry, quantitative RT-PCR, Fos activation, neuronal tract tracing, intracerebroventricular antagonist injection, and serum prolactin measurement were used.

Results: 

TIP39 mRNA and peptide expressions are markedly elevated in neurons of the PIL in lactating rat dams. In addition, Fos appears in the nuclei of TIP39 neurons of the PIL in response to suckling. TIP39 fibers are abundant in the hypothalamic para-, periventricular and arcuate nuclei. Posterior intralaminar thalamic TIP39 neurons project to these hypothalamic nuclei based on the injections of anterograde and retrograde tracers to the PIL and the above-mentioned hypothalamic nuclei, respectively. Subsequently, a PTH2 receptor antagonist injected into the lateral ventricle was shown to dose-dependently inhibit suckling-induced elevation of plasma prolactin level in mother rats.

Conclusion: 

TIP39 neurons in the PIL are ideally positioned to receive sensory input from nipples and transfer this information to the mediobasal hypothalamus. Their activation in mothers suggests that they indeed receive input related to suckling. The blockade of prolactin release by an antagonist of the PTH2 receptor suggests that TIP39 plays a physiological role in the regulation of suckling-induced prolactin release.

Support: 

NKTH-OTKA K67646, OTKA NNF2 85612 and NK72929