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Bio- and Immunoactive Luteinizing Hormone Responses to Low Doses of Gonadotropin-Releasing Hormone (GnRH): Dose-Response Curves in GnRH-Deficient Men^*

DANIEL I. SPRATT, JOEL S. FINKELSTEIN, THOMAS M. BADGER, JAMES P. BUTLER and WILLIAM F. CROWLEY, JR.

Reproductive Endocrine Unit and the Vincent Research Laboratories, Departments of Medicine and Gynecology, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114

Address requests for reprints to: William F. Crowley, Jr., M.D., Reproductive Endocrine Unit, Massachusetts General Hospital, Vincent 1, Boston, Massachusetts 02114.

Previous investigations of the effects of GnRH on pituitary LH responses in normal men required pharmacological doses of GnRH to avoid the confounding effects of endogenous GnRH secretion and employed nonphysiological dose intervals. To examine the role of GnRH in determining both the qualitative and quantitative nature of physiological LH responses, we studied five GnRH-deficient men in whom pituitary and gonadal function had been normalized with GnRH replacement. Both bio- and immunoactive LH responses were evaluated in these men after a wide range of GnRH doses (7.5–250 ng/kg) administered at a physiological frequency (every 2 h), while gonadal steroid levels were within the normal adult male range. In addition, the amplitude and contour of the immunoactive LH pulses were compared to those of 15 normal men to assure that these experiments achieved physiological pituitary responses. The relationship between bio- and immunoactive LH was compared between patients, between doses as the amount of GnRH was increased, and within pulses of LH.

As the dose of GnRH was increased, both bio- and immunoactive LH responses increased in a log-linear fashion when assessed by both amplitude (r = 0.96 for bioactive LH and r =0.98 for immunoactive LH) and area under the curve (r = 0.99 for bioactive LH and r = 0.97 for immunoactive LH). GnRH doses of 7.5 and 25 ng/kg produced LH responses with amplitudes similar to those in normal men.

The relationship between bio- and immunoactive LH between patients and between differing doses of GnRH was analyzed by comparing the slopes of lines fit to individual bioactive vs. immunoactive LH plots after each dose of GnRH in each patient. There was a marked variation in the relationship of bio- to immunoactive LH between patients (P < 0.005). No change was found in thebiopotency of LH as the dose of GnRH was increased (P < 0.10). Finally, no variation of thebioactivity of LH was evident within individual pulses.

We conclude that 1) a log-linear relationship exists between doses of GnRH that produce physiological LH pulses and both bio- and immunoactive LH responses; 2) the bioactivity of secreted LH varies markedly between patients; 3) the relative bioactivity of LH in an individual does not change as the dose of GnRH is increased; and 4) no change in bioactivity of LH responses was demonstrated within pulses of LH.

^* This work was supported in part by Grants HD-15788, HD-19899, and RR-1066 from the NIH and the Vincent Memorial Research Fund.

Present address: Department of Environmental Science and Physiology, Harvard School for Public Health, Boston, MA.

Received July 25, 1985.

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