Evaluation of Serum Insulin-like Factor 3 Quantification by LC-MS/MS as a Biomarker of Leydig Cell Function.

Albrethsen, Jakob; Johannsen, Trine Holm; Jørgensen, Niklas Rye; Frederiksen, Hanne; Sennels, Henriette P; Jørgensen, H.; Fahrenkrug, Jan; Petersen, Jørgen Holm; Linneberg, Allan; Nordkap, Loa; Bang, Anne Kirstine; Andersson, Anna‐Maria; Juul, Anders

doi:10.1210/clinem/dgaa145

Cited by 31 publications

(30 citation statements)

References 35 publications

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“…18 There is little detailed information about mean INSL3 concentration at an intermediate age between puberty and established adulthood, though one recent study of Danish men has supported higher INSL3 values in young adulthood. 19 Whilst the primary aim of this retrospective study was to assess the relationship between seminal parameters and Leydig cell functional capacity, the parameters available also allowed a third aim of determining possible factors linked to the large inter-individual variation in circulating INSL3 measured. Besides seminal, anthropometric and hormonal parameters, the Swedish cohort of 18-year-old men was also assessed for androgen receptor polymorphisms to elucidate a further possible interaction with androgen action.…”

Section: Introductionmentioning

confidence: 99%

Male seminal parameters are not associated with Leydig cell functional capacity in men

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Male seminal parameters are not associated with Leydig cell functional capacity in men

et al. 2021

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show abstract

“…This is not the case. We recently found a close agreement between the circulating level of INSL3 measured by TRFIA and LC-MS/MS in a direct comparison of human serum samples ( 12 ), and, secondly, the measured mean concentration of INSL3 is similar in two large studies using either the TRFIA or MS methods on serum cohorts from healthy adult men ( 9 , 33 ). This supports that in healthy men, INSL3 is predominately present as the smaller heterodimer.…”

Section: The Structure Of Human Insl3mentioning

confidence: 61%

“…We have recently developed an MS-based method for serum INSL3 ( 12 ). The LOD of the LC-MS/MS assay is 0.03 μg/L, the intra-assay variation is <9%, and the long-term variation (2 years) is <15% ( 9 , 12 ). As opposed to the immunoassays, the MS-based method can only detect the smaller insulin-like form of INSL3 without the C-domain.…”

Section: The Structure Of Human Insl3mentioning

confidence: 99%

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Mass Spectrometry Supports That the Structure of Circulating Human Insulin-Like Factor 3 Is a Heterodimer

2020

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The structure of the testicular peptide hormone insulin-like factor 3 (INSL3) has been the subject of discussion for more than a decade. Some studies support that the central C-domain of INSL3 is proteolytically removed and that INSL3 is secreted by the testicular Leydig cells into circulation as a small heterodimer consisting of an A- and a B-chain linked by two disulfide bridges. Other studies support that the INSL3 peptide remains uncleaved and that the predominant structure of circulating INSL3 is the larger pro-form. Furthermore, the structure of INSL3 could differ between species, and both structural forms of INSL3 could, in principle, be present in circulation. Recently, we have developed a mass spectrometry (MS)-based method for INSL3 in human serum that provides new information about the structure of circulating INSL3. Based on recent and newly presented data, we argue that in healthy men, the common, and probably the only, form of circulating INSL3 is the smaller AB heterodimer. For the first time, we demonstrate that the same analytical principle, with slight modifications, can also be applied to sera from other species, and we show that the INSL3 AB heterodimer is also present in serum from rodents. Improved understanding of the structure and biochemistry of circulating INSL3 could be valuable for the interpretation of INSL3 as a marker for reproductive and developmental disorders in humans and domesticated animals.

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“…Based on the timeline of reported biological effects and pharmacokinetics, the post-injection performance was evaluated 24 h after (Day 1) the injection, around the time point where maximal pharmacological activity was expected (Forsdahl et al, 2015). Serum testosterone concentrations vary throughout the day in a diurnal cycle (Piro et al, 1973;Albrethsen et al, 2020). Therefore, to minimize the influence of circadian hormonal changes on the performance measurements, the injections and testing sessions took place around the same time of the day.…”

Section: Exercise Protocolmentioning

confidence: 99%

An Intramuscular Injection of Mixed Testosterone Esters Does Not Acutely Enhance Strength and Power in Recreationally Active Young Men

Solheim

Mørkeberg²,

Juul

et al. 2020

Front. Physiol.

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Purpose: Limited data are available on the acute performance-enhancing effects of single-dose administration of testosterone in healthy humans. Studies of testosterone administrations to healthy humans are rare due to the difficult nature and necessity of close clinical monitoring. However, our unique physiological experimental facilities combined with close endocrinological collaboration have allowed us to safely complete such a study. We tested the hypothesis that an intramuscular injection of 250 mg mixed testosterone esters (TEs) enhances physical performance in strength and power exercises acutely, measured 24 h after injection. Additionally, we investigated whether the basal serum testosterone concentration influences the performance in countermovement jump (CMJ), 30-s all out cycle sprint, and one-arm isometric elbow flexion. Methods: In a randomized, double-blind, placebo-controlled design, 19 eugonadal men received either a TE (n = 9, 23 ± 1 years, 183 ± 7 cm, 83 ± 10 kg) or a PLA (n = 10, 25 ± 2 years, 186 ± 6 cm, 82 ± 14 kg) injection. Hormonal levels and the performance in CMJ, 30-s all out cycle sprint, and one-arm isometric elbow flexion were measured before and 24 h after injection. Results: Firstly, an intramuscular injection of 250 mg mixed TEs did not enhance the vertical jump height in a CMJ test, peak power, mean power, and fatigue index in a 30-s all-out cycle sprint or rate of force development and maximal voluntary contraction in a one-arm isometric elbow flexion 24 h post-injection. Secondly, baseline testosterone levels appeared not to influence performance in strength and power exercises to a large extent in healthy, recreationally active young men. Conclusion: A single intramuscular injection of 250 mg mixed TEs has no acute ergogenic effects on strength and power performance in recreationally active, young men. This novel information has implication for basic physiological understanding. Whether the same applies to an elite athlete population remains to be determined. If so, this would have implications for anti-doping efforts aiming to determine the most cost-efficient testing programs.

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Evaluation of Serum Insulin-like Factor 3 Quantification by LC-MS/MS as a Biomarker of Leydig Cell Function.

Cited by 31 publications

References 35 publications

Male seminal parameters are not associated with Leydig cell functional capacity in men

Male seminal parameters are not associated with Leydig cell functional capacity in men

Mass Spectrometry Supports That the Structure of Circulating Human Insulin-Like Factor 3 Is a Heterodimer

An Intramuscular Injection of Mixed Testosterone Esters Does Not Acutely Enhance Strength and Power in Recreationally Active Young Men

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