Biologically Active Luteinizing Hormone Is Secreted in Episodic Pulsations that Vary in Relation to Stage of the Menstrual Cycle*

To characterize the physiological pattern(s) of bioactive LH secretion in normal women, serial blood samples were withdrawn at frequent intervals in each of six women at three different stages of the menstrual cycle. Plasma LH concentrations were quantitated in each sample by both rat interstitial cell testosterone ( RICT ) bioassay and immunoassay (RIA). When the resulting RICT and RIA LH profiles were systematically compared, we found that mean (and integrated) plasma concentrations of bioactive LH were approximately 2-fold higher than immunoactive LH levels at all stages of the menstrual cycle. In addition, unequivocal prominent pulsations of bioactive LH could be demonstrated in these women throughout the normal menstrual cycle. For all stages of the menstrual cycle, bioactive to immunoactive LH ratios within LH pulses were significantly (P less than 0.01) increased over these ratios in the interpulse periods. The frequency of bioactive LH pulses increased dramatically from 0.44 +/- 0.24 (+/- SD) pulses/h in the early follicular phase to 1.21 +/- 0.07 pulses/h in the late follicular phase (P less than 0.003), and then declined to only 0.25 pulses/h in the luteal phase (P less than 0.001). Notably, significant discordance existed between bioactive and immunoactive LH pulses, with 30% of immunoactive and 14% of bioactive LH pulses occurring alone. In conclusion, using the RICT , we demonstrated that biologically active LH is secreted in discrete episodic pulsations in normal women. Estimates of the bioactive to immunoactive LH ratio indicate that these pulses of LH are preferentially enriched in biologically active compared to immunoactive hormone. The properties of bioactive LH pulses are under physiological control, since the amplitude and frequency of bioactive LH pulses vary significantly in relation to phases of the menstrual cycle. Since significant discordance exists between immunoactive and bioactive LH pulsations in normal women, we suggest that estimates of the circulating concentrations of biologically active LH (rather than immunoactive LH alone) are necessary to characterize fully physiological patterns of LH secretion during the menstrual cycle.