Endocrine Abstracts

Fertility is critically dependent upon episodic gonadotropin hormone secretion. Recent studies using genetic mouse models have identified that a population of kisspeptin neurons located in the arcuate nucleus (ARN) represent the gonadotropin-releasing hormone (GnRH) pulse generator in both males and females. These cells exhibit abrupt periods of synchronised activity for 1-2 min that, in turn, activate GnRH neuron processes to release GnRH over a similar time scale to drive pulsatile luteinizing hormone secretion. The remarkable similarities between the activity patterns of mouse ARN kisspeptin neurons and early unidentified multi-unit recordings in the monkey infundibular nucleus by Knobil and colleagues, indicate that the kisspeptin pulse generator is highly conserved in mammals. Studies using in vivo CRISPR-Cas9 gene editing further demonstrate that the primary site of estrogen negative feedback in controlling GnRH secretion occurs through estrogen receptor alpha expressed by ARN kisspeptin neurons. These and other in vivo approaches are finally allowing the once enigmatic pulse generator to be characterized and explored.