Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenism of healthy aging in men.

Veldhuis, Johannes D.; Urban, Randall J.; Lizarralde, German; Johnson, Michael L.; Iranmanesh, Ali

doi:10.1210/jcem.75.3.1517359

Cited by 107 publications

(72 citation statements)

References 27 publications

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“…The patients were, however, slightly but not significantly older (median 21.0 years) than controls. It is well established that the number of both the LH and FSH peaks increase with increasing age (38)(39)(40). However, when excluding the two oldest individuals (aged 34.4 and 39.1 years) in the Klinefelter group leaving the patients between 16.0 and 21.6 years of age and comparing these with the controls the number of peaks did not change for either FSH or LH.…”

Section: Discussionmentioning

confidence: 94%

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

Aksglæde

Jensen

Carlsen

et al. 2008

European Journal of Endocrinology

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Objective: The regulation of normal sexual maturation and reproductive function is dependent on a precise hormonal regulation at hypothalamic, pituitary, and gonadal levels. The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes. Design: Cross-sectional study. Methods: In this study, 7 untreated patients with primary gonadal insufficiency due to SRY-positive 46,XX (nZ4) and 46,XXY karyotypes (nZ3) aged 18.8 years and 25 age-matched healthy controls participated. Reproductive hormones, testicular size, and overnight LH and FSH serum profiles and overnight urine LH and FSH excretion were determined. Results: Basal LH and FSH secretion was elevated 6.3-and 25.4-fold respectively in the patients and the amount of LH and FSH secreted per burst were 2.0-and 6.6-fold elevated. We found significantly more LH but not FSH peaks per 24 h, as estimated by the Weibull l analysis. There was no difference between approximate entropy ratios or Weibull g analyses indicating comparable orderliness and regularity of LH and FSH secretion. Overnight urinary LH and FSH excretion was significantly elevated in patients compared with controls and correlated significantly with calculated total overnight LH and FSH secretion respectively, thus validating deconvolution. Conclusion: In this group of patients with severe hypergonadotropic hypogonadism due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and FSH secretion were associated with significantly more LH peaks per 24 h in comparison with healthy controls. Thus, our data indicate that in patients with Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary-gonadal axis has undergone functional changes.European Journal of Endocrinology 158 803-810

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Section: Discussionmentioning

confidence: 94%

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

Aksglæde

Jensen

Carlsen

et al. 2008

European Journal of Endocrinology

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“…Blood samples were allowed to clot at room temperature, and sera were frozen at Ϫ20°C. LH concentrations were assayed in duplicate by specific LH ␤-subunit-directed two-site monoclonal immunoradiometric assay (IRMA) (Nichols Laboratories, San Juan Capistrano, CA) (21,49). The sensitivity of the LH assay is 0.2 IU/l (First International Reference Preparation), and there is Ͻ0.03% cross-reactivity with free ␣-FSH or TSH (42,49,50,52).…”

Section: Methodsmentioning

confidence: 99%

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

Liu¹,

Pincus²,

Keenan³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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In the present study, we contrasted in vivo linkages within and between these two axes using methods without linearity assumptions. We examined 11 young (21-31 yr) and 8 older (62-74 yr) men who underwent frequent (every 2.5 min) blood sampling overnight for paired measurement of LH and testosterone and 35 adults (17 women and 18 men; 26 -77 yr old) who underwent adrenocorticotropic hormone (ACTH) and cortisol measurements every 10 min for 24 h. To mirror physiological interactions, hormone secretion was first deconvolved from serial concentrations with a waveform-independent biexponential elimination model. Feedforward synchrony, feedback synchrony, and the difference in feedforward-feedback synchrony were quantified by the cross-approximate entropy (X-ApEn) statistic. These were applied in a forward (LH concentration template, examining pattern recurrence in testosterone secretion), reverse (testosterone concentration template, examining pattern recurrence in LH secretion), and differential (forward minus reverse) manner, respectively. Analogous concentration-secretion X-ApEn estimates were calculated from ACTH-cortisol pairs. X-ApEn, a scale-and model-independent measure of pattern reproducibility, disclosed 1) greater testosterone-LH feedback coordination than LH-testosterone feedforward synchrony in healthy men and significant and symmetric erosion of both feedforward and feedback linkages with aging; 2) more synchronous ACTH concentration-dependent feedforward than feedback drive of cortisol secretion, independent of gender and age; and 3) enhanced detection of bidirectional physiological regulation by in vivo pairwise concentration-secretion compared with concentrationconcentration analyses. The linking of relevant biological input to output signals and vice versa should be useful in the dissection of the reciprocal control of neuroendocrine systems or even in the analysis of other nonendocrine networks.gonadal; adrenal; synchrony AGING IS MARKED BY A 30 -50% decline in systemic testosterone concentrations in healthy community-dwelling men, as recognized nearly 50 yr ago (11,46). Subsequent longitudinal (5,9,20) and population-based cross-sectional (2, 7, 19, 37) studies have corroborated relative androgen depletion in aging men. Other epidemiological data have correlated hypoandrogenemia with sarcopenia, osteopenia, reduced physical stamina, sexual dysfunction, impaired quality of life, and (possibly) depressive mood and cognitive impairment (46). Recent interventional studies suggest that reduced testosterone availability may be relevant to frailty in aging men (18,36). In parallel with therapeutic notions, mechanistic investigations are needed to determine why aging is associated with hypoandrogenemia. Few studies have appraised the effect of aging on nonlinear interactions, which are expected from time-delayed asymptotic dose-response connections among gonadotropin-releasing hormone (GnRH), LH, and testosterone. Recent developments of regulatory statistics and their validation in mathematical, laborat...

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“…166,168,169,212 ± 214,216 ± 221 Obesity thus seems to cause a state of`hypogonadotropic hypogonadism', similar to that observed at old age. 209,222 This state cannot be explained entirely by a negative feedback of bioavailable T on pituitary LH secretion, but must involve additional mechanisms, which are only partially understood ( Figure 2). 221,223,224 One such additional mechanism may be a decrease in pituitary GH secretion and total IGF-1 levels, which is generally observed in obese men.…”

Section: Physiological Mechanismsmentioning

confidence: 99%

Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

Kaaks

Lukanova

Sommersberg

2000

Prostate Cancer Prostatic Dis

103

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We present a review of the epidemiological evidence for relations of prostate cancer risk to circulating total and bioavailable androgens, to alterations in the metabolism of insulin-like growth factor-1 (IGF-1), and to anthropometric indices of longitudinal growth (body stature) and overweight. In addition, we review the physiological inter-relationships between insulin, growth hormone/IGF-1 axis, and sex steroid metabolism, as well as the associations of bioavailable sex steroid levels with overweight and obesity. A ®rst conclusion of this review is that, taken together, epidemiological studies have provided little support for the hypothesis that prostate cancer risk is increased in men with elevated total or biovailable testosterone (T). Although one prospective study showed an increased risk in men with low plasma sex hormone-binding globulin (SHBG) and with elevated plasma T for given levels of SHBG, this was not con®rmed by results from other cohort studies. A second conclusion is that overweight, which is generally associated with moderate reductions in both total and bioavailable plasma T, appears to be unrelated to any signi®cant increase or decrease in prostate cancer risk. However, signi®cant increases in risk have been observed for men with a taller body stature, or with elevated plasma IGF-1. IGF-1 may directly enhance prostate tumorigenesis by inhibiting apoptosis and by stimulating cell proliferation. In addition, IGF-1 downregulates the synthesis of SHBG, and enhances sex steroid synthesis. Therefore, we do not entirely rule out that due to an elevation of plasma IGF-1 levels, men at increased risk of prostate cancer also have mildly elevated plasma bioavailable T, which epidemiological studies may have failed to demonstrate because of methodological problems. Prostate Cancer and Prostatic Diseases (2000) 3, 157±172.

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Attenuation of luteinizing hormone secretory burst amplitude as a proximate basis for the hypoandrogenism of healthy aging in men.

Cited by 107 publications

References 27 publications

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or 46,XX karyotypes.

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review

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