Journal of Clinical Endocrinology & Metabolism, Vol 76, 648-654, Copyright © 1993 by Endocrine Society

ARTICLES

Evidence for attenuation of hypothalamic gonadotropin-releasing hormone (GnRH) impulse strength with preservation of GnRH pulse frequency in men with chronic renal failure

JD Veldhuis, MJ Wilkowski, AD Zwart, RJ Urban, G Lizarralde, A Iranmanesh and WK Bolton
Department of Internal Medicine, University of Virginia Health Sciences center, Charlottesville 22908.

To investigate the nature of putative disturbances in pulsatile gonadotropin (LH) secretion in men with chronic renal failure, we undertook blood sampling at 10-min intervals for 24 h in 9 hemodialysis- dependent uremic men and 16 community- and age-matched controls. Serum LH concentrations were measured in a 2-site immunoradiometric assay, which does not cross-react with free alpha or LH beta-subunit and correlates well with an in vitro Leydig cell bioassay. Deconvolution analysis was applied to calculate the number, amplitude, mass, and duration of spontaneous LH release episodes and simultaneously estimate the half-life of endogenous LH in each subject. We observed that: 1) the estimated half-life of immunoradiometric LH removal from plasma averaged 103 +/- 11 min in normal and 207 +/- 29 min in uremic men (P < 0.01); 2) the number of LH secretory bursts was slightly higher in uremic than healthy men (e.g. 20 +/- 2.2 vs. 15 +/- 1.0 secretory bursts/24 h, respectively; P = 0.05); 3) the mass of LH secreted per burst was approximately 50% lower in chronic renal failure than in health, namely 1.4 +/- 0.18 vs. 2.8 +/- 0.42 IU/L (P < 0.01); 4) the decrease in the mass of LH secreted per burst was not due to a decline in LH secretory burst amplitude, but rather an attenuation of LH secretory burst duration (4.8 +/- 0.35 min in uremic vs. 11 +/- 1.3 min in normal men; P < 0.001); 5) the mean 24-h serum immunoradiometric LH concentration was significantly higher in uremia at 5.7 +/- 0.68 vs. 3.6 +/- 0.41 IU/L in controls (P = 0.017); and 6) serum estradiol concentrations were increased in uremia, but total and free testosterone concentrations did not differ significantly between the two subject groups. In response to synthetic GnRH (10 micrograms, administered iv after the 24-h basal sampling period), the mean mass of immunoradiometric LH released within each calculated LH secretory burst was similar in uremic (n = 8) and normal (n = 21) individuals. We conclude that uremia is accompanied by a specific defect in the pulsatile mode of LH secretion, which is marked by an abbreviation of LH secretory burst duration and a consequent fall in the mass of LH secreted per spontaneous release episode. There is no overall decline in LH secretory pulse frequency or gonadotroph responsiveness to a submaximally effective dose of exogenous GnRH. Such findings are consistent with diminished hypothalamic GnRH impulse strength.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				J. M. Kaufman and A. Vermeulen The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications Endocr. Rev., October 1, 2005; 26(6): 833 - 876. [Abstract] [Full Text] [PDF]

				A. Iranmanesh and J. D. Veldhuis Combined Inhibition of Types I and II 5 {alpha}-Reductase Selectively Augments the Basal (Nonpulsatile) Mode of Testosterone Secretion in Young Men J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4232 - 4237. [Abstract] [Full Text] [PDF]

				K. Klein, M. Daschner, M. Vogel, J. Oh, T. J. Feuerstein, and F. Schaefer Impaired Autofeedback Regulation of Hypothalamic Norepinephrine Release in Experimental Uremia J. Am. Soc. Nephrol., July 1, 2005; 16(7): 2081 - 2087. [Abstract] [Full Text] [PDF]

				A. Karagiannis and F. Harsoulis Gonadal dysfunction in systemic diseases Eur. J. Endocrinol., April 1, 2005; 152(4): 501 - 513. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Bae, R. S. Swerdloff, A. Iranmanesh, and C. Wang Experimentally Induced Androgen Depletion Accentuates Ethnicity-Related Contrasts in Luteinizing Hormone Secretion in Asian and Caucasian Men J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1632 - 1638. [Abstract] [Full Text] [PDF]

				P. Y. Liu, S. M. Pincus, D. M. Keenan, F. Roelfsema, and J. D. Veldhuis Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R440 - R446. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Iranmanesh, and T. Mulligan Age and Testosterone Feedback Jointly Control the Dose-Dependent Actions of Gonadotropin-Releasing Hormone in Healthy Men J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 302 - 309. [Abstract] [Full Text] [PDF]

				D. M. Keenan, W. S. Evans, and J. D. Veldhuis Control of LH secretory-burst frequency and interpulse-interval regularity in women Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E938 - E948. [Abstract] [Full Text] [PDF]

				J. C. Lopez-Alvarenga, T. Zarinan, A. Olivares, J. Gonzalez-Barranco, J. D. Veldhuis, and A. Ulloa-Aguirre Poorly Controlled Type I Diabetes Mellitus in Young Men Selectively Suppresses Luteinizing Hormone Secretory Burst Mass J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5507 - 5515. [Abstract] [Full Text] [PDF]

				A. Schmidt, A. Luger, and W. H. Horl Sexual hormone abnormalities in male patients with renal failure Nephrol. Dial. Transplant., March 1, 2002; 17(3): 368 - 371. [Full Text] [PDF]

				T. Mulligan, A. Iranmanesh, and J. D. Veldhuis Pulsatile iv Infusion of Recombinant Human LH in Leuprolide-Suppressed Men Unmasks Impoverished Leydig-Cell Secretory Responsiveness to Midphysiological LH Drive in the Aging Male J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5547 - 5553. [Abstract] [Full Text] [PDF]

				G. Van den Berghe, F. Weekers, R. C. Baxter, P. Wouters, A. Iranmanesh, R. Bouillon, and J. D. Veldhuis Five-Day Pulsatile Gonadotropin-Releasing Hormone Administration Unveils Combined Hypothalamic-Pituitary-Gonadal Defects Underlying Profound Hypoandrogenism in Men with Prolonged Critical Illness J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3217 - 3226. [Abstract] [Full Text] [PDF]

				F. SCHAEFER, M. VOGEL, G. KERKHOFF, J. WOITZIK, M. DASCHNER, and O. MEHLS Experimental Uremia Affects Hypothalamic Amino Acid Neurotransmitter Milieu J. Am. Soc. Nephrol., June 1, 2001; 12(6): 1218 - 1227. [Abstract] [Full Text]

				J. D. Veldhuis, A. Zwart, T. Mulligan, and A. Iranmanesh Muting of Androgen Negative Feedback Unveils Impoverished Gonadotropin-Releasing Hormone/Luteinizing Hormone Secretory Reactivity in Healthy Older Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 529 - 535. [Abstract] [Full Text]

				M. Menjívar, M. Cárdenas, G. Ortiz, and J. Pedraza-Chaverrí Fertility Diminution in Female Rats with Experimental Chronic Nephrosis Biol Reprod, November 1, 2000; 63(5): 1549 - 1554. [Abstract] [Full Text]

				M. Bergendahl, J. A. Aloi, A. Iranmanesh, T. M. Mulligan, and J. D. Veldhuis Fasting Suppresses Pulsatile Luteinizing Hormone (LH) Secretion and Enhances Orderliness of LH Release in Young but Not Older Men J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1967 - 1975. [Abstract] [Full Text]

				J. Hangaard, M. Andersen, E. Grodum, O. Koldkjær, and C. Hagen Pulsatile Luteinizing Hormone Secretion in Patients with Addison's Disease. Impact of Glucocorticoid Substitution J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 736 - 743. [Abstract] [Full Text]

				P. A. Clark, A. Iranmanesh, J. D. Veldhuis, and A. D. Rogol Comparison of Pulsatile Luteinizing Hormone Secretion Between Prepubertal Children and Young Adults: Evidence for a Mass/Amplitude-Dependent Difference Without Gender or Day/Night Contrasts J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2950 - 2955. [Abstract] [Full Text] [PDF]

				A. D. Zwart, A. Iranmanesh, and J. D. Veldhuis Disparate Serum Free Testosterone Concentrations and Degrees of Hypothalamo-Pituitary-Luteinizing Hormone Suppression Are Achieved by Continuous Versus Pulsatile Intravenous Androgen Replacement in Men: A Clinical Experimental Model of Ketoconazole-Induced Reversible Hypoandrogenemia with Controlled Testosterone Add-Back J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2062 - 2069. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Iranmanesh, E. Samojlik, and R. J. Urban Differential Sex Steroid Negative Feedback Regulation of Pulsatile Follicle-Stimulating Hormone Secretion in Healthy Older Men: Deconvolution Analysis and Steady- State Sex-Steroid Hormone Infusions in Frequently Sampled Healthy Older Individuals J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1248 - 1254. [Abstract] [Full Text] [PDF]