Effects of prolactin on hypothalamic supraoptic neurones: evidence for modulation of STAT5 expression and electrical activity.

OBJECTIVES: The study investigated the role of prolactin (PRL) in modulating STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO) nucleus of male rats. METHODS: Evidence of expression of STAT5 in the SO nucleus was investigated by immunocytochemical methods. Effect of blocking prolactin receptors on STAT 5 expression was investigated by Western blotting following transfection of SO neurones with a dominant negative mutant form of the PRL receptor. Prolactin-induced changes in electrical activity were investigated by extracellular recording in hypothalamic slices. RESULTS: A high proportion of SO neurones in male rats expressed immunoreactive STAT5. Levels of activated STAT5 within the SO nucleus of PRL-treated rats was reduced following transfection with a dominant negative mutant form of the PRL receptor, as compared to rats transfected with wild type PRL receptor. Electrophysiological recordings from the SO nucleus in horizontal brain slices showed that approximately 25% of neurones were responsive to PRL, with both inhibitory and excitatory effects being observed. Cells displaying PRL responses included pharmacologically-identified oxytocinergic neurones. CONCLUSIONS: Collectively, the results suggest that central PRL targets neurones of the SO nucleus, influencing both activation of the JAK-STAT signalling pathway and neuronal excitability. Whilst the functional significance of this interaction remains to be established, it might be important in co-ordinating oxytocin secretion with physiological events associated with changes in plasma PRL, or in mediating a feedback loop in the oxytocinergic regulation of lactotrophs.

Central oxytocin potentiates excitatory responses of oxytocin neurones to stimulation of the dorsomedial hypothalamic nucleus in the suckled rat.

Experiments were undertaken to investigate the effects of intracerebroventricular (i.c.v.) oxytocin (OT) on the response of supraoptic OT neurones to stimulation of the dorsomedial nucleus (DMH), in the suckled lactating rat. Under control conditions, the majority of OT neurones displayed either weak excitation to DMH stimulation, or no response. Following i.c.v. OT injection, all neurones showed a pronounced long-latency (70-115 ms) excitatory response, and the number of spikes evoked per stimulus pulse was significantly increased. This increased excitatory response was accompanied by facilitation of the milk-ejection reflex. Some OT neurones also displayed a short latency (8-13 ms) excitation to DMH stimulation, but this was unaffected by i.c.v. OT. In conclusion, the facilitation of bursting in OT neurones by i.c.v. OT is associated with potentiation of long-latency excitatory responses evoked by DMH stimulation.