The median eminence detects and responds to circulating prolactin in the male mouse.

In addition to its established lactational roles, prolactin acts on multiple target tissues and its circulating levels are responsive to a range of physiological stimuli. The present study used immunohistochemistry to demonstrate that systemic administration of prolactin activates target cells in the arcuate nucleus and median eminence of the male mouse. Prolactin receptor stimulation results in the phosphorylation and thus activation of the signal transducer and activator of transcription (STAT)5 pathway. Interestingly, although, in the arcuate nucleus, this response was localised to cell nuclei, the median eminence displayed both nuclear and diffuse, non-nuclear, phospho-STAT5 (pSTAT5) staining. Dual-label immunostaining demonstrated that, although the majority of nuclear pSTAT5 within the median eminence was located within vimentin-positive tanycytes, the non-nuclear staining occurred primarily in neuronal (βIII tubulin immunoreactive) elements. This conclusion was supported by the marked reduction of this signal in prolactin-treated mice lacking neuronal prolactin receptors. A smaller reduction was also seen in animals lacking prolactin receptors on GABAergic but not glutamatergic neurones. These findings identify a new prolactin target tissue and, in doing so, support the proposal that the median eminence has a sensory role in addition to its established secretory function. The physiological significance of this prolactin response is unknown, although its rapidity (maximum within 2 minutes of i.p. injection) suggests that it may enable the early detection of an increase in circulating prolactin. It is also possibile that non-nuclear prolactin-generated pSTAT5 in the median eminence may have a local, non-transcriptional, action. To this end, we used Evans Blue dye to demonstrate that elevated prolactin appears to reduce median eminence permeability and also that this effect is lost in animals lacking neuronal prolactin receptors.