Pulsatile luteinizing hormone secretion in normal female mice and in hypogonadal female mice with preoptic area...

Pulsatile LH secretion is driven by GnRH, the hypothalamic hormone that is lacking in the hypogonadal mutant mouse. Preoptic area grafts containing GnRH neurons correct many reproductive deficits in hypogonadal mice. In this study we evaluated the pattern of LH secretion in hypogonadal female mice with preoptic area grafts (hpg/POA) and in normal female mice. Normal females were ovariectomized at 10 weeks of age, and hpg/POA mice were ovariectomized 4 months after graft surgery. Three weeks later, all mice received intracardial catheters. The next day, sequential blood samples were obtained every 10 min for 4 h from the awake, freely moving mice. At ovariectomy, normal and hpg/POA ovarian weights were 8.6 +/- 0.9 and 7.1 +/- 1.2 mg, respectively. Significant LH pulses were detected in 9 of 10 normal mice and in 9 of 13 hpg/POA mice. Pulse frequency (normal, 0.86 +/- 0.13; hpg/POA, 0.61 +/- 0.13 pulse/h) and interpeak interval (normal, 81.7 +/- 20.3; hpg/POA, 93.2 +/- 24.0 min) were not significantly different (P greater than 0.2), but mean plasma LH levels (normal, 1.07 +/- 0.16 ng/ml; hpg/POA, 0.49 +/- 0.08 ng/ml; P less than 0.005) and mean LH pulse amplitude (normal, 1.92 +/- 0.53; hpg/POA, 0.63 +/- 0.28; P less than 0.05) were significantly lower in the hpg/POA mice. The lower mean LH level and LH pulse amplitude in ovariectomized hpg/POA mice are consistent with the inability of most of these mice to show increased LH secretion after castration. The findings indicate that preoptic area brain grafts are capable of supporting episodic LH release in the hypogonadal mouse and suggest the presence of a functional GnRH pulse generator in the majority of mice with grafts.