Mode of Secretion of Bioactive Luteinizing Hormone in Man*

The episodic nature of gonadotropin secretion was originally defined by RIA of circulating LH concentrations. We analyzed the pulsatile release of biologically active LH by measuring plasma LH concentrations in the rat interstitial cell testosterone bioassay. A computer algorithm to discriminate true biological signals (LH pulses) from background variation was applied to serially sampled LH data from seven men and seven postmenopausal women. Our results indicate the following. 1) In all subjects, mean bioactive LH values were considerably higher than immunoactive levels, (41.4 +/- 15.1 and 450 +/- 243 mIU/ml vs. 10.2 +/- 2.3 and 83 +/- 35 for men and postmenopausal women, respectively). There was a corresponding 4-fold increase in the total area under the bioactive LH secretion profile compared with that defined for the immunoactive hormone. 2) The absolute amplitude of the bioactive LH peaks was 0.5- to 11-fold higher than the immunoactive values. 3) Although the majority of the LH peaks were coincident by bioassay and RIA, significant dissociation occurred in 20% and 28% of the total LH peaks (rat interstitial cell testosterone bioassay and RIA) in men and postmenopausal women, respectively. 4) Significant increases in the bioactive to immunoactive ratio over interpulse bioactive to immunoactive levels occurred in 98% of the pulses in the men and 83% of those in postmenopausal women. Also, in two men, peaks of LH bioactivity exceeding 100 mIU were followed by major increases in serum testosterone concentrations. These findings demonstrate the value of bioactive LH determinations and indicate that LH is secreted in pulses of high biological activity. The in vitro LH bioassay provides a sensitive and appropriate estimate of functionally active LH in the circulation.