Journal of Clinical Endocrinology & Metabolism, Vol 65, 929-941, Copyright © 1987 by Endocrine Society

ARTICLES

Operating characteristics of the male hypothalamo-pituitary-gonadal axis: pulsatile release of testosterone and follicle-stimulating hormone and their temporal coupling with luteinizing hormone

JD Veldhuis, JC King, RJ Urban, AD Rogol, WS Evans, LA Kolp and ML Johnson
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.

To appraise the physiological pattern(s) of episodic testosterone and FSH release in man, we withdrew blood samples at 10-min intervals for 24-36 h in a total of 15 normal men. We subjected the resulting FSH (15 men) and testosterone (5 men) time series to 3 statistically based and mathematically independent procedures for detecting hormone pulsatility, viz. Cluster analysis, the Detect program, and Fourier transformation. The Cluster technique disclosed discrete testosterone and FSH peaks occurring at mean (+/- SEM) interpulse intervals of 112 +/- 14 and 85 +/- 3.4 min, respectively. These values were not significantly different from the mean LH interpulse interval of 95 +/- 11 min. The average durations of the testosterone and FSH pulsations were 90 +/- 11 and 59 +/- 3 min, respectively. The mean testosterone pulse amplitude reached a maximal value of 910 +/- 92 ng/dL (31.5 +/- 3.2 nmol/L), which represented a mean increase of 242 +/- 26 ng/dL (8.4 +/- 0.9 nmol/L) above the preceding nadir. FSH pulses had a maximum of 7.2 +/- 0.3 IU/L, and an incremental amplitude of 1.3 +/- 0.1 IU/L. An independent pulse detection procedure. Detect, yielded a testosterone pulse frequency of 12.3 +/- 0.8 pulses/day [P = NS vs. Cluster program (13 +/- 1.9 pulses/day)]. The Cluster and Detect estimates of FSH pulse frequency were also similar, viz. 16 +/- 1.9 and 16 +/- 0.6 pulses/day. Further analysis by Fourier transformation revealed significant circadian periodicities for serum testosterone, FSH, and LH, which had mean nyctohemeral amplitudes of 185 ng/dL (6.4 nmol/L), 0.38 IU/L, and 1.3 IU/L, respectively. Cross-correlation analyses disclosed significantly positive uncorrected cross-correlations between LH and testosterone that were maximal at a testosterone lag of 60 min (range, 50-70 min). To eliminate high intrinsic autocorrelations within the testosterone and LH time series, stepwise autoregressive fitting was employed. The resulting partial cross-correlation matrices indicated that LH concentrations at any given instant were significantly positively correlated to testosterone concentrations lagged by 10 and 20 min. Similarly, contemporaneous LH and FSH concentrations were significantly positively correlated (r = 0.40-0.89; P less than 0.001). Moreover, autoregressive modeling disclosed significantly positive partial cross-correlations between LH and FSH at a FSH lag of 10 min. In summary, we have identified significant pulsatile as well as circadian (24-h) patterns of testosterone and FSH release in normal men.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				N. Pitteloud, A. A. Dwyer, S. DeCruz, H. Lee, P. A. Boepple, W. F. Crowley Jr., and F. J. Hayes Inhibition of Luteinizing Hormone Secretion by Testosterone in Men Requires Aromatization for Its Pituitary But Not Its Hypothalamic Effects: Evidence from the Tandem Study of Normal and Gonadotropin-Releasing Hormone-Deficient Men J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 784 - 791. [Abstract] [Full Text] [PDF]

				J. Iqbal, O. Latchoumanin, and I. J. Clarke Rapid in Vivo Effects of Estradiol-17{beta} in Ovine Pituitary Gonadotropes Are Displayed by Phosphorylation of Extracellularly Regulated Kinase, Serine/Threonine Kinase, and 3',5'-Cyclic Adenosine 5'-Monophosphate-Responsive Element-Binding Protein Endocrinology, December 1, 2007; 148(12): 5794 - 5802. [Abstract] [Full Text] [PDF]

				P. Y. Takahashi, P. Votruba, M. Abu-Rub, K. Mielke, and J. D. Veldhuis Age Attenuates Testosterone Secretion Driven by Amplitude-Varying Pulses of Recombinant Human Luteinizing Hormone during Acute Gonadotrope Inhibition in Healthy Men J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3626 - 3632. [Abstract] [Full Text] [PDF]

				P. Crabbe, V. Bogaert, D. De Bacquer, S. Goemaere, H. Zmierczak, and J. M. Kaufman Part of the Interindividual Variation in Serum Testosterone Levels in Healthy Men Reflects Differences in Androgen Sensitivity and Feedback Set Point: Contribution of the Androgen Receptor Polyglutamine Tract Polymorphism J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3604 - 3610. [Abstract] [Full Text] [PDF]

				J. D. Meeker, L. Godfrey-Bailey, and R. Hauser Relationships Between Serum Hormone Levels and Semen Quality Among Men From an Infertility Clinic J Androl, May 1, 2007; 28(3): 397 - 406. [Abstract] [Full Text] [PDF]

				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]

				P. Y. Liu, P. Y. Takahashi, P. D. Roebuck, A. Iranmanesh, and J. D. Veldhuis Aging in Healthy Men Impairs Recombinant Human Luteinizing Hormone (LH)-Stimulated Testosterone Secretion Monitored under a Two-Day Intravenous Pulsatile LH Clamp J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5544 - 5550. [Abstract] [Full Text] [PDF]

				R. G. Smith Development of Growth Hormone Secretagogues Endocr. Rev., May 1, 2005; 26(3): 346 - 360. [Abstract] [Full Text] [PDF]

				P. Y. Takahashi, P. Y. Liu, P. D. Roebuck, A. Iranmanesh, and J. D. Veldhuis Graded Inhibition of Pulsatile Luteinizing Hormone Secretion by a Selective Gonadotropin-Releasing Hormone (GnRH)-Receptor Antagonist in Healthy Men: Evidence That Age Attenuates Hypothalamic GnRH Outflow J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2768 - 2774. [Abstract] [Full Text] [PDF]

				B. J. Sagarin Reconsidering Evolved Sex Differences in Jealousy: Comment on Harris (2003) Personality and Social Psychology Review, February 1, 2005; 9(1): 62 - 75. [Abstract] [PDF]

				J. D. Veldhuis, A. Iranmanesh, and D. M. Keenan Erosion of Endogenous Testosterone-Driven Negative Feedback on Pulsatile Luteinizing Hormone Secretion in Healthy Aging Men J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5753 - 5761. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis and A. Iranmanesh Pulsatile Intravenous Infusion of Recombinant Human Luteinizing Hormone under Acute Gonadotropin-Releasing Hormone Receptor Blockade Reconstitutes Testosterone Secretion in Young Men J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4474 - 4479. [Abstract] [Full Text] [PDF]

				P. M. Crofton, A. E. M. Evans, A. M. Wallace, N. P. Groome, and C. J. H. Kelnar Nocturnal Secretory Dynamics of Inhibin B and Testosterone in Pre- and Peripubertal Boys J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 867 - 874. [Abstract] [Full Text] [PDF]

				R. A. Anderson and D. T. Baird Male Contraception Endocr. Rev., December 1, 2002; 23(6): 735 - 762. [Abstract] [Full Text] [PDF]

				J. A. Schnorr, M. J. Bray, and J. D. Veldhuis Aromatization Mediates Testosterone's Short-Term Feedback Restraint of 24-Hour Endogenously Driven and Acute Exogenous Gonadotropin-Releasing Hormone-Stimulated Luteinizing Hormone and Follicle-Stimulating Hormone Secretion in Young Men J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2600 - 2606. [Abstract] [Full Text] [PDF]

				R. Luboshitzky, Z. Zabari, Z. Shen-Orr, P. Herer, and P. Lavie Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1134 - 1139. [Abstract] [Full Text]

				J. H. Mendelson, M. B. Sholar, A. J. Siegel, and N. K. Mello Effects of Cocaine on Luteinizing Hormone in Women during the Follicular and Luteal Phases of the Menstrual Cycle and in Men J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 972 - 979. [Abstract] [Full Text]

				J. D. Veldhuis, A. Iranmanesh, M. Godschalk, and T. Mulligan Older Men Manifest Multifold Synchrony Disruption of Reproductive Neurohormone Outflow J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1477 - 1486. [Abstract] [Full Text]

				J. D. Veldhuis, Ali Iranmanesh, Thomas Mulligan, and Steven M. Pincus Disruption of the Young-Adult Synchrony between Luteinizing Hormone Release and Oscillations in Follicle-Stimulating Hormone, Prolactin, and Nocturnal Penile Tumescence (NPT) in Healthy Older Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3498 - 3505. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, A. Iranmanesh, L. M. Demers, and T. Mulligan Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3506 - 3514. [Abstract] [Full Text] [PDF]

				E. Carlsen, C. Olsson, J. H. Petersen, A.-M. Andersson, and N. E Skakkebæk Diurnal Rhythm in Serum Levels of Inhibin B in Normal Men: Relation to Testicular Steroids and Gonadotropins J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1664 - 1669. [Abstract] [Full Text]

				R. Mitamura, K. Yano, N. Suzuki, Y. Ito, Y. Makita, and A. Okuno Diurnal Rhythms of Luteinizing Hormone, Follicle-Stimulating Hormone, and Testosterone Secretion before the Onset of Male Puberty J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 29 - 37. [Abstract] [Full Text]

				J. Yang, D. W. Long, N. Inpanbutr, and W. L. Bacon Effects of Photoperiod and Age on Secretory Patterns of Luteinizing Hormone and Testosterone and Semen Production in Male Domestic Turkeys Biol Reprod, November 1, 1998; 59(5): 1171 - 1179. [Abstract] [Full Text]

				D. M. Keenan and J. D. Veldhuis A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary-Leydig cell axis Am J Physiol Endocrinol Metab, July 1, 1998; 275(1): E157 - E176. [Abstract] [Full Text] [PDF]

				S. M. Pincus, J. D. Veldhuis, T. Mulligan, A. Iranmanesh, and W. S. Evans Effects of age on the irregularity of LH and FSH serum concentrations in women and men Am J Physiol Endocrinol Metab, November 1, 1997; 273(5): E989 - E995. [Abstract] [Full Text] [PDF]

				T. Mulligan, A. Iranmanesh, M. L. Johnson, M. Straume, and J. D. Veldhuis Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1997; 273(4): R1407 - R1413. [Abstract] [Full Text] [PDF]

				C. Foresta, P. Bordon, M. Rossato, R. Mioni, and J. D. Veldhuis Specific Linkages Among Luteinizing Hormone, Follicle-Stimulating Hormone, and Testosterone Release in the Peripheral Blood and Human Spermatic Vein: Evidence for Both Positive (Feed-Forward) and Negative (Feedback) Within-Axis Regulation J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 3040 - 3046. [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]

				J.B. Powers, E.A. Steel, J.B. Hutchison, M.H. Hastings, J. Herbert, and A.P. Walker Photoperiodic Influences on Sexual Behavior in Male Syrian Hamsters J Biol Rhythms, March 1, 1989; 4(1): 61 - 78. [Abstract] [PDF]