Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice
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 supp...
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/94570 |
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| author | Eleni Hackwell Sharon R Ladyman Jenny Clarkson H James McQullian Ulrich Boehm Allan Edward Herbison Rosemary Brown David R Grattan |
| author_facet | Eleni Hackwell Sharon R Ladyman Jenny Clarkson H James McQullian Ulrich Boehm Allan Edward Herbison Rosemary Brown David R Grattan |
| author_sort | Eleni Hackwell |
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| description | 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. |
| format | Article |
| id | doaj-art-e4c6951ee09c4bed8efe01cce9246f07 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-e4c6951ee09c4bed8efe01cce9246f072025-01-17T13:18:53ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.94570Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in miceEleni Hackwell0Sharon R Ladyman1Jenny Clarkson2H James McQullian3Ulrich Boehm4https://orcid.org/0000-0003-2436-6907Allan Edward Herbison5https://orcid.org/0000-0002-9615-3022Rosemary Brown6David R Grattan7https://orcid.org/0000-0001-5606-2559Centre for Neuroendocrinology, Dunedin, New Zealand; Department of Anatomy, Dunedin, New ZealandCentre for Neuroendocrinology, Dunedin, New Zealand; Department of Anatomy, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandCentre for Neuroendocrinology, Dunedin, New Zealand; Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New ZealandCentre for Neuroendocrinology, Dunedin, New Zealand; Department of Anatomy, Dunedin, New ZealandSaarland University School of Medicine, Centre for Molecular Signalling (PZMS), Experimental Pharmacology, Homburg, GermanyDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomCentre for Neuroendocrinology, Dunedin, New Zealand; Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New ZealandCentre for Neuroendocrinology, Dunedin, New Zealand; Department of Anatomy, Dunedin, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New ZealandThe 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.https://elifesciences.org/articles/94570neuroendocrinologyhypothalamuskisspeptinprolactinlactationinfertility |
| spellingShingle | Eleni Hackwell Sharon R Ladyman Jenny Clarkson H James McQullian Ulrich Boehm Allan Edward Herbison Rosemary Brown David R Grattan Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice eLife neuroendocrinology hypothalamus kisspeptin prolactin lactation infertility |
| title | Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice |
| title_full | Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice |
| title_fullStr | Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice |
| title_full_unstemmed | Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice |
| title_short | Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice |
| title_sort | prolactin mediates a lactation induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice |
| topic | neuroendocrinology hypothalamus kisspeptin prolactin lactation infertility |
| url | https://elifesciences.org/articles/94570 |
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