Contemporary Aspects of Discrete Peak-Detection Algorithms. I. The Paradigm of the Luteinizing Hormone Pulse Signal in Men*

Urban, Randall J.; Evans, William S.; Rogol, Alan D.; Kaiser, Donald L.; Johnson, Mark; Veldhuis, Johannes D.

doi:10.1210/edrv-9-1-3

Cited by 229 publications

(195 citation statements)

References 71 publications

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“…48 Sampling of LH at frequent intervals of 2-5 minutes in three old men during the hours of sleep clearly displayed the diminution of high amplitude pulses. 49,50 A blunted circadian rhythm of LH in the aged has also been demonstrated. 51,52 Recent Aging per se has a primarily testicular effect where reduced testosterone is accompanied by elevated LH.…”

Section: -70yrsmentioning

confidence: 88%

The aging of the endocrine hypothalamus and its dependent endocrine glands

Batrinos¹

2012

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Section: -70yrsmentioning

confidence: 88%

The aging of the endocrine hypothalamus and its dependent endocrine glands

Batrinos¹

2012

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“…Because mean and plateau LH concentrations did not differ during 1-and 2-h pulses of rhLH, we infer that the dynamics of T production at a given mean LH concentration depend on LH pulse frequency. Whether such dynamics convey specific regulatory information to T-target cells is not known (48). However, in one analysis, pulses of T yielded lower mean T levels and suppressed LH secretion less than continuous T infusions in young men (58).…”

Section: R998 Pulsatile Versus Continuous Lh Stimulationmentioning

confidence: 99%

Analysis of the impact of intravenous LH pulses versus continuous LH infusion on testosterone secretion during GnRH-receptor blockade

Veldhuis¹,

Liu

Takahashi

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Analysis of the impact of intravenous LH pulses versus continuous LH infusion on testosterone secretion during GnRH-receptor blockade. Am J Physiol Regul Integr Comp Physiol 303: R994 -R1002, 2012. First published September 19, 2012 doi:10.1152/ajpregu.00314.2012.-Gonadotrophin-releasing hormone (GnRH) pulsatility is required for optimal luteinizing hormone (LH) secretion, but whether LH pulsatility is required for physiological testosterone (T) secretion is not known. To test the postulate that pulses of recombinant human (rh) LH stimulate greater T secretion than continuous infusion of the same dose, a potent selective GnRH antagonist was administered overnight to 19 healthy men ages 18 -49 yr. Subjects then received saline or rhLH intravenously continuously or as 6-min pulses intravenously every 1 or 2 h at the same total dose. Blood was sampled every 10 min for 10 h to quantify T responses. For the four interventions, the descending rank order of mean LH and mean T concentrations was 1-h ϭ 2-h rhLH pulses Ͼ continuous rhLH Ͼ saline (P Ͻ 10 Ϫ3 ). Plateau LH and T concentrations correlated positively (R 2 ϭ 0.943, P ϭ 0.029) as did LH concentrations and LH half-lives (R 2 ϭ 0.962, P ϭ 0.019). Percentage pulsatile T secretion assessed by deconvolution analysis (Keenan DM, Takahashi PY, Liu PY, Roebuck PD, Nehra AX, Iranmanesh A, Veldhuis JD. Endocrinology 147: 2817-2828, 2006) was the highest (P ϭ 0.019), and half-time to attain peak T concentrations was the shortest (P Ͻ 10 Ϫ6 ), for 1-h rhLH pulses. Approximate entropy (a pattern-regularity measure) revealed more orderly T secretion for 1-than 2-h rhLH pulses (P ϭ 0.0076). Accordingly, a pulsatile LH signal, while not obligatory to maintain mean T concentrations, controls the mean plasma LH concentration and determines quantifiable patterns of T secretion. These data introduce the question whether blood T patterns in turn supervise distinctive target-tissue responses.pulse; gonadotropin; human; testis; testosterone LOW TESTOSTERONE (T) concentrations increase the clinical risk of sarcopenia, osteopenia, diminished libido and potentia, visceral adiposity, decreased aerobic capacity, and (possibly) impaired cognitive function (30). Reduced T availability may result from reduced gonadotrope stimulation by hypothalamic gonadotrophin-releasing hormone (GnRH), attenuated biosynthesis of luteinizing hormone (LH), heightened T clearance, greater T negative feedback, and/or blunted testicular responses to LH (32,33). In addition, hypoandrogenemia in some conditions such as aging is associated with disorderly LH secretion patterns (30 -32, 36, 51) and smaller more frequent circhoral LH pulses (18,32,36). Whether small frequent LH pulses or continuous LH delivery into the bloodstream is less effective than larger infrequent LH pulses in driving T secretion is not known. The issue is central to the broader theme of pulsatility regulation and action in endocrine systems (17,20,54). Indeed, growth hormone (GH), ACTH, parathyroid hormone (PTH), insulin, and oxytocin driv...

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“…Multiple regulatory factors (e.g., sex steroids, polysynaptic neuronal inputs) coordinate hypothalamic secretion of bursts of gonadotropin-releasing hormone (GnRH) in women and men (1). Pulsatile release of GnRH into the hypothalamic-pituitary portal microcirculation in turn stimulates (feedforward) episodes of pituitary secretion of luteinizing hormone (LH).…”

Section: Introductionmentioning

confidence: 99%

Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis

Mulligan

Iranmanesh

Kerzner

et al. 1999

European Journal of Endocrinology

108

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Objective: To examine the possibility that lower serum bioavailable testosterone concentrations, without increased LH release, in healthy older men, reflects hypothalamic GnRH deficiency. Design: We used a randomized, double-blind, placebo-controlled design. Methods: We treated each of five young (ages 20-34 years) and five older (ages 60-78 years) men with 2 weeks of randomized infusions of saline or pulsatile GnRH (100 ng/kg i.v. every 90 min). Results: At baseline (saline infusion), older men had more LH pulses (young compared with old, 10 Ϯ 0.6 compared with 15 Ϯ 1, P = 0.0026) per 24 h, reduced fractional LH pulse amplitude (219 Ϯ 17% compared with 167 Ϯ 40%, P = 0.0376), and more disorderly hormone release as judged by approximate entropy (ApEn) (LH, P Յ 0.0001; testosterone, P Յ 0.0047). In response to pulsatile i.v. GnRH infusions, serum 24-h LH concentrations (measured by immunoradiometric assay (IRMA)), increased equivalently in young and older men (to 7.3 Ϯ 1.2 and 7.2 Ϯ 1.8 IU/l respectively). GnRH treatment also normalized LH pulse frequency and amplitude, ApEn, and plasma biologically active LH (pooled) concentrations. In contrast, 24-h testosterone concentrations failed to increase equivalently in older men (young compared with old, 869 Ϯ 88 compared with 517 Ϯ 38 ng/dl, P = 0.0061), reflecting lower testosterone peak maxima (995 Ϯ 108 compared with 583 Ϯ 48 ng/dl, P = 0.0083) and interpeak nadirs (750 Ϯ 87 compared with 427 Ϯ 26 ng/dl, P = 0.0073). Conclusions:We have demonstrated that, in older men, successful reconstitution of 24-h pituitary (bioactive) LH output and pulsatile (IRMA) LH release patterns could be achieved by a fixed exogenous GnRH pulse signal, thereby implicating altered endogenous hypothalamic GnRH release in the relative hypogonadotropism of aging. The failure of testosterone concentrations to increase concomitantly points to a simultaneous Leydig cell defect. We conclude that aging in men is marked by a dual defect in the central nervous system-pituitary-Leydig cell axis.

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Contemporary Aspects of Discrete Peak-Detection Algorithms. I. The Paradigm of the Luteinizing Hormone Pulse Signal in Men*

Cited by 229 publications

References 71 publications

The aging of the endocrine hypothalamus and its dependent endocrine glands

The aging of the endocrine hypothalamus and its dependent endocrine glands

Analysis of the impact of intravenous LH pulses versus continuous LH infusion on testosterone secretion during GnRH-receptor blockade

Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis

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