Hyperprolactinaemia during lactation is a consequence of the sucking stimulus and in part due to reduced prolactin negative feedback. To date the mechanisms involved in this diminished sensitivity to prolactin feedback are unknown, but may involve changes in prolactin signal transduction within tuberoinfundibular dopaminergic (TIDA) neurons. Therefore we investigated STAT5 signaling in the TIDA neurons of lactating rats.

Dual label confocal immunofluorescence studies were used to determine the intracellular distribution of STAT5 within TIDA neurons in the dorsomedial arcuate nucleus. In lactating rats with pups removed for 16 h, injection of oPRL significantly (P < 0.05) increased the STAT5 nuclear/cytoplasmic (N/C) ratio compared with vehicle treated mothers. In contrast, oPRL injection did not increase the STAT5 N/C ratio in lactating mothers with pups, demonstrating that prolactin signal transduction through STAT5 is reduced in TIDA neurons in the presence of pups.

To investigate possible mechanisms involved in reduced prolactin signaling, we examined the expression of Suppressors of Cytokine Signaling (SOCS) proteins. Northern analysis on whole hypothalamus showed that CIS (cytokine-inducible SH2-domain-containing protein), but not SOCS1 or SOCS3, mRNA expression was significantly (P < 0.01) upregulated in suckled lactating rats. Semi-quantitative RT-PCR on arcuate nucleus micropunches also showed up-regulation of CIS transcripts. Immunofluorescence studies demonstrated that CIS is expressed in all TIDA neurons in the dorsomedial arcuate nucleus, and the intensity of CIS staining in these neurons is significantly (P < 0.05) increased in lactating rats with sucking pups. Together these results support the hypothesis that loss of sensitivity to prolactin negative feedback during lactation is a result of increased CIS expression in TIDA neurons.