Katja Czieselsky, Mel Prescott, Robert Porteous, Pauline Campos, Jenny Clarkson, Frederik J. Steyn, Rebecca E. Campbell, Allan E. Herbison

Using a new tail-tip bleeding procedure and a sensitive ELISA, we describe here the patterns of luteinizing hormone (LH) secretion i) throughout the mouse estrous cycle, ii) in ovariectomized mice, iii) in ovariectomized, estradiol-treated mice that model estrogen negative and positive feedback, and iv) in transgenic GNR23 mice that exhibit allele-dependent reductions in GnRH neuron number. Pulsatile LH secretion was evident at all stages of the estrous cycle with LH pulse frequency being approximately one pulse per hour in metestrous, diestrous, and proestrous mice but much less frequent at estrus (<1 pulse/4h). Ovariectomy resulted in substantial increases in basal and pulsatile LH secretion with pulses occurring approximately every 21 min. Chronic treatment with "negative feedback" estradiol-filled capsules returned LH pulse frequency to intact follicular phase levels although pulse amplitude remained elevated. On the afternoon of proestrus, the LH surge was found to begin in a highly variable manner over a 4h range, lasting for >3h. In contrast, ovariectomized, estradiol-treated "positive feedback" mice exhibited a relatively uniform surge onset at ∼0.5h prior to lights out. Gonadectomized wildtype and heterozygous GNR23 (∼200 GnRH neurons) male mice exhibited an LH pulse every 60 min. Homozygous GNR23 mice (∼80 GnRH neurons) had very low basal LH concentrations but continued to exhibit small amplitude LH pulses every 90 min. These studies provide the first characterization in mice of pulse and surge modes of LH secretion across the estrous cycle and demonstrate that very few GnRH neurons are required for pulsatile LH secretion.