Oral Presentation ESA-SRB-APEG-NZSE 2022

Prolactin-induced suppression of gonadotrophin secretion during lactation (#240)

Eleni CR Hackwell 1 , Sharon R Ladyman 1 2 , Rosemary SE Brown 3 , Allan E Herbison 4 , Dave R Grattan 1 2
  1. Centre for Neuroendocrinology and Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
  2. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
  3. Centre for Neuroendocrinology and Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
  4. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

In mammals, lactation is associated with a period of infertility, in order for a mother’s metabolic resources to be directed towards caring for her newborn, rather than supporting another pregnancy. This lactational infertility is characterized by the suppression of kisspeptin neurons leading to a reduction in gonadotrophin secretion and a consequent cessation of ovulation. Lactation is accompanied by chronically elevated levels of the anterior pituitary hormone prolactin. Despite elevated prolactin, per se, being a well-recognized cause of infertility, the specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, is unclear. The aim of the present study was to determine whether prolactin action specifically on arcuate kisspeptin neurons suppresses gonadotroph secretion during lactation in mice. To investigate this we conditionally deleted the prolactin receptor (Prlr) from arcuate kisspeptin neurons (Prlrlox/lox/Kiss1Cre) and examined estrous cyclicity, luteinizing hormone (LH) secretion and arcuate kisspeptin neuronal activity. Neuronal activity was monitored in real time using kisspeptin neuron-specific GCaMP6 fiber photometry. As reported previously1, in the diestrous virgin state, periodic events of elevated intracellular calcium (indicative of synchronous activity of the arcuate kisspeptin population) precede the release of LH, occurring approximately once an hour. As expected, control animals showed lactation-induced infertility, and only resumed normal estrous cyclicity following weaning (>20 days of lactation). These animals show a corresponding complete suppression of synchronised Ca2+ events from kisspeptin neurons till day 14 of lactation. In contrast, Prlrlox/lox/Kiss1Cre mice showed early resumption of estrous cyclicity within 4-17 days of lactation (p<0.0001) which was preceded by early reactivation of the arcuate kisspeptin population. These observations show dynamic variation in activity of arcuate kisspeptin neurons associated with the hormonal changes of lactation, and provide evidence that prolactin action on those neurons is necessary for the suppression of gonadotrophin secretion during lactation.

  1. 1. McQuillian, H. J., Han, S. Y., Cheong, I., Herbison, A. E. (2019). GnRH pulse generator activity across the estrous cycle of female mice. Endocrinology. 160(6):1480-1491.