Poster Presentation The International Congress of Neuroendocrinology 2014

Evidence that Prolactin acts on a relatively small subpopulation of RFRP-3 Neurons to suppress their activity and stress responses (#237)

Caroline Ancel 1 , Ilona C Kokay 1 , Amanda Wyatt 1 , Mohammed Z Rizwan 1 , Greg M Anderson 1
  1. Otago University, Dunedin, New Zealand
At the end of pregnancy, elevated prolactin levels stimulate milk production. During lactation, elevated circulating prolactin also feeds back to the brain to suppress stress responses, but the neuroanatomical pathways involved remain unknown. The hypothalamic-pituitary-adrenal axis is controlled by corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus. RFamide-related peptide-3 (RFRP-3) neurons project to this region from the dorsomedial hypothalamus. Our recent results indicate that RFRP-3 administration promotes anxiety-related behaviours and restraint-induced corticosterone secretion in female rats and mice, and conversely overcomes prolactin-induced anxiolytic behaviour and suppression of restraint-induced corticosterone secretion by prolactin. Moreover, centrally-administered RFRP-3 increases Crh mRNA expression and serum ACTH concentrations. These effects are overcome by co-treatment with RFRP-3 receptor antagonists, such that antagonist-treated animals are more anxiolytic than untreated controls. In addition, RFRP-3 fibres make close appositions with paraventricular CRH neurons, a subgroup of which was found to express the gene for the RFRP-3 receptor, Gpr147. These observations led us to hypothesise that RFRP-3 neurons form a conduit between prolactin’s site of action and the stress axis. In the present study, we show that during  lactation, prolactin suppresses RFRP-3 cell numbers and Rfrp mRNA levels. Using an immunomagnetic separation method, we found that prolactin receptor-long form mRNA is present, albeit in low levels, in purified RFRP-3 cells from rats and mice. To quantify the percentage of RFRP-3 neurons expressing this receptor, we performed double in situ hybridization for Rfrp and prolactin receptor-long form. In diestrus rats, just under 10% of Rfrp cells co-expressed prolactin receptor. Taken together, these results indicate that the RFRP-3 system may directly convey prolactin’s effects to the HPA axis but, given the relatively low prolactin receptor colocalisation, indirect prolactin inputs may also be involved.