The Subfornical Organ: A Novel Site for Prolactin Action

Abstract

Prolactin (PRL) is a peptide hormone which performs over 300 biological functions, including those that require binding to prolactin receptor (PRL-R) in neurons within the central nervous system (CNS) (Bole-Feysot, Goffin, Edery, Binart, & Kelly, 1998). In order to enter the CNS, circulating PRL must overcome the blood-brain barrier. As such, areas of the brain that do not possess a blood-brain barrier, such as the subfornical organ (SFO), are optimally positioned to interact with systemic PRL. The SFO has been classically implicated in energy and fluid homeostasis but has the potential to influence estrous cyclicity and gonadotropin release, which are also functions of PRL. We sought to confirm and characterize the expression of PRL-R in the SFO as well as identify the effects of PRL application on membrane excitability of dissociated SFO neurons. Using real-time quantitative PCR, we identified PRLR mRNA in the SFO in male and female Sprague Dawley rats. PRL-R expression did not significantly differ between males (n=10) and females (n=24), between juveniles (n=10) and sexually mature (n=24) rats, or across the estrous cycle (n=19). Patch-clamp recordings were then obtained using juvenile male rats to further investigate the actions of PRL at the SFO. Dissociated SFO neurons perfused with 10 pM to 1 μM PRL resulted in three subpopulations of neurons which either depolarized, hyperpolarized, or did not respond to PRL application (n=111). The proportion and magnitude of responses were independent of PRL concentration. Furthermore, a majority of SFO neurons showed a reduction in the transient K+ current following PRL exposure. The stability in response to PRL and expression of PRL-R in the SFO suggests PRL function is conserved across physiological states and circulating PRL concentrations, although further studies are required to elucidate the nature of PRL function in the SFO.