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In Vivo Dynamics of Luteinizing Hormone Secretion and Clearance in Man: Assessment by Deconvolution Mechanics^*

Departments of Internal Medicine and Pharmacology, University of Virginia School of Medicine Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Box 202, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908.

The dynamics of LH secretion and clearance were studied in vivo in eight healthy young men using a novel multiple parameter deconvolution procedure to resolve underlying secretion and clearance rates simultaneously from serial serum immunoactive LH concentrations. This deconvolution analysis disclosed random LH secretory bursts occurring at a mean (±SEM) interpulse interval of 72 ± 5 min. The frequency of these secretory bursts was 6.9 ± 0.6 episodes/8 h. Each resolved LH secretory event had an average half-duration of only 7.8 ± 0.5 min, which was remarkably shorter than the LH concentration peak duration of 60 ± 6 min. The maximal LH secretory rate achieved within a secretory burst averaged 0.40 ± 0.05 mIU/min-mL (0.14 IU/min·L), which corresponded to a mass of LH released of 3.2 ± 0.3 mlU/mL distribution vol (IU/L). By linear regression analysis, both the maximal rate and mass of LH released per secretory burst were positively correlated with the duration of the subsequent interpulse interval (P < 0.001). In physiological experiments, the mass of LH released per secretory burst was increased by iv GnRH injections or primary gonadal failure, and decreased by sc administration of a selective GnRH antagonist (Nal,Glu-GnRH). The mean endogenous LH production rate calculated by deconvolution [180 ± 40 mlU/min (0.18 IU/min)] was not different from a nominal value of 228 ± 80 mlU/min (0.228 IU/min) extrapolated from earlier steady state LH infusions. Deconvolution estimated single phase half-times of endogenous LH disappearance of 87 ± 8 min, were in general harmony with values of 44–106 min obtained previously in four LH-deficient men injected with purified LH. Moreover, creation of synthetic LH series using our deconvolution estimates yielded 24-h LH pulse profiles similar quantitatively and qualitatively to those in normal men.

In summary, we applied a new multiple parameter deconvolution procedure to immunoactive LH pulse profiles to discern the nature of physiological LH secretory events and estimate endogenous LH disappearance rates. These studies in normal men have revealed that 1) LH secretory bursts occur every 72 min; their mean half-duration is 7.8 min; and 3.2 mlU/mL (3.2 IU/L) are released per secretory peak; 2) amplitudes of in vivo LH secretory bursts are augmented in primary gonadal failure and/or by exogenous GnRH injections and attenuated by a GnRH antagonist; 3) the duration of a postsecretory pause is proportional to the amplitude of the preceding LH secretory burst; and (4) 95% of total daily LH release occurs in only 5 h/day. We conclude that observed physiological profiles of episodic LH pulsations in serum can be accounted for by punctuated random LH secretory bursts of finite and determinable amplitude, duration, and frequency.

^* This work was supported in part by NIH Grant RR-00847 to the Clinical Research Center of the University of Virginia, Research Career Development Award 1-K04-HD-00634 (to J.D.V.), NIH Grants AM- 30302 and GM-28928 (to M.L.J.), Diabetes and Research Training Center Grant 5-P60-AM-22125-05, and NIH-supported Clinfo Data Reduction Systems.

Received October 14, 1987.

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