PROLACTIN PARTICIPATION ON NEURONAL SUBTYPE SPECIFICATION IN SH-SY5Y NEUROBLASTOMA CELLS

Prolactin (PRL) is a pleiotropic peptide hormone that has been shown to play an important role in the central nervous system. Beyond its classical endocrine functions, PRL has been shown to exert neuroprotective effects against excitotoxic insults and to promote neurogenesis in specific brain regions. However, its role in neuronal differentiation and phenotypic specification remains incompletely understood. The aim of this study was to evaluate whether PRL induces neuronal differentiation toward a phenotype distinct from that triggered by retinoic acid (RA) in the human neuroblastoma cell line SH-SY5Y. Therefore, SH-SY5Y Cells were treated for seven days with PRL (0.1, 1, or 10 ng/mL), RA (10 µM), and a combination of both. Neuronal differentiation and maturation were assessed by immunohistochemistry, Western blotting, and RT-PCR, focusing on markers associated with neurotransmitter synthesis (choline acetyltransferase, ChAT; tyrosine hydroxylase, TH) and neuronal maturation and synaptic organization (MAP2 and PSD-95) expression proteins and mRNA. PRL treatment promoted neuronal differentiation and induced a cellular subtype specification distinct from that elicited by RA. PRL exposure resulted in expression of prolactin receptor (PRLR) isoforms, MAP2, and PSD-95 at both mRNA and protein levels, supporting enhanced neuronal maturation and synaptic marker expression. These findings indicate that PRL not only confers neuroprotective effects as previously reported, but also actively drives neuronal differentiation toward a specific phenotype. PRL may therefore represent a promising therapeutic candidate for neurological disorders associated with neuronal damage and impaired differentiation.