Development of Gonadotropin-Releasing Hormone-1 Secretion in Mouse Nasal Explants

Pulsatile release of GnRH-1 is critical to stimulate gonadotropes of the anterior pituitary. Thissecretory pattern seems to be inherent to GnRH-1 neurons, however, the mechanisms underlyingsuch episodical release remain unknown. In monkey nasal explants, the GnRH-1 population ex-hibits synchronized calcium events with the same periodicity as GnRH-1 release, suggesting a link,though the sequence of events was unclear. GnRH-1 neurons in mouse nasal explants also exhibitsynchronized calcium events. In the present work, GnRH-1 release was assayed in mouse nasalexplants using radioimmunology and its relationship with calcium signaling analyzed. GnRH-1neurons generated episodical release as early as 3 din vitro(div) and maintained such releasethroughout the period studied (3–21 div). The pulse frequency remained constant, suggesting thatthe pulse generator is operative at an early developmental stage. In contrast, pulse amplitudeincreased 2-fold between 3 and 7 div, and again between 7 and 14 div, suggesting maturation insynthesizing and/or secretory mechanisms. To evaluate these possibilities, total GnRH-1 contentwas measured. Only a small increase in GnRH-1 content was detected between 7 and 14 div,whereas a large increase occurred between 14 and 21 div. These data indicate that GnRH-1 contentwas not a limiting factor for the amplitude of the pulses at 7 div but that the secretory mechanismsmature between 3 and 14 div. The application of kisspeptin-10 revealed the ability of GnRH-1neurons to integrate signals from natural ligands into a secretory response. Finally, simultaneoussampling of medium and calcium imaging recordings indicated that the synchronized calciumevents and secretory events are congruent.(Endocrinology150: 3221–3227, 200