Tuberoinfundibular peptide 39 (TIP39)-containing neurons are activated during lactation in the posterior intralaminar complex of the thalamus (PIL) in mother rats and, during this period they express TIP39 peptide and mRNA at higher levels than control females and pup-deprived dams.

We describe the topographical distribution of TIP39 neurons in relation to calcium-binding proteins and report that calbindin but not calretinin or parvalbumin coexpress with TIP39 in the PIL. Injection of the anterograde tracer biotinylated dextran amine into the PIL resulted in labeled axon terminals in medial hypothalamic nuclei including the arcuate, peri-, paraventricular and dorsomedial hypothalamic nuclei, where the receptor of TIP39, the parathyroid-hormone 2 receptor (PTH2R) is also present in relatively high concentrations. Furthermore, a high number of retrogradely labeled TIP39 neurons in the PIL were seen after injection of the retrograde tracer cholera toxin beta subunit in the medial hypothalamic nuclei confirming that these neurons project to the medial hypothalamus. Subsequently, the function of TIP39-containing neuronal projections was addressed. A genetically modified lentivirus expressing GFP for visualization of infected cells and the PTH2R antagonist HYWH-TIP39 (as well as a control GFP-tagged virus) was injected into the medial hypothalamus of female rats, 2 weeks before mating. Blood samples were taken via jugular catheters on 12 days postpartum for measuring of serum prolactin levels. Dams injected with HYWH-GFP lentivirus showed significantly reduced basic prolactin levels. Furthermore, suckling resulted in lower prolactin levels in these animals after returning the pups following a 4h separation period. These results strongly suggest that TIP39 neurons in the PIL project to the medial hypothalamus and regulate prolactin release in rat dams.

Support: Bolyai Fellowship, OTKA NNF85612 and K100319 grants for AD, OTKA-81522 grant for GMN, OTKA CK80180 grant for MP, and the NIMH Intramural Research Program for TBU.