Differential Actions of Prolactin on Electrical Activity and Intracellular Signal Transduction in Hypothalamic Neurons

Abstract

In many tissues, including brain, prolactin action is predominantly mediated by the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway, leading to changes in gene transcription. However, prolactin can also exert rapid actions on electrical activity of hypothalamic neurons. Here, we investigate whether both responses occur in a single cell type, focusing on three specific populations known to be influenced by prolactin: GnRH neurons, tuberoinfundibular dopamine (TIDA) neurons, and neurons in the anteroventral-periventricular nucleus in female mice. We performed phosphorylated STAT5 (pSTAT5) immunohistochemistry to identify prolactin-responsive neurons after in vivo prolactin treatment. In addition, we carried out in vitro electrophysiology in slices from transgenic mice expressing green fluorescent protein driven by the GnRH or tyrosine hydroxylase promoters as well as from C57BL/6J mice to assess acute electrical responses to prolactin. Approximately 88% of TIDA neurons expressed pSTAT5 in diestrous mice, rising to 97% after prolactin treatment. All TIDA neurons also showed a rapid increase in firing rate after prolactin treatment. In contrast, very few GnRH neurons (11%) showed pSTAT5 in response to prolactin, and none showed a change in electrical activity. Finally, in the anteroventral-periventricular nucleus, most neurons (69%) responded to prolactin treatment with an increase in pSTAT5, but only 2/38 (∼5%) showed changes in electrical activity in response to prolactin. These observations show that prolactin recruits different combinations of electrical and transcriptional responses in neurons depending upon their anatomical location and phenotype. This may be critical in establishing appropriate responses to prolactin under different physiological conditions.