PT - JOURNAL ARTICLE AU - Hackwell, Eleni C.R. AU - Ladyman, Sharon R. AU - Clarkson, Jenny AU - McQuillan, H. James AU - Boehm, Ulrich AU - Herbison, Allan E. AU - Brown, Rosemary S.E. AU - Grattan, David R. TI - Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice AID - 10.1101/2024.01.26.577359 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.01.26.577359 4099 - http://biorxiv.org/content/early/2024/07/31/2024.01.26.577359.short 4100 - http://biorxiv.org/content/early/2024/07/31/2024.01.26.577359.full AB - The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.Competing Interest StatementThe authors have declared no competing interest.