Serum insulin-like factor 3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose human chorionic gonadotropin: a randomized, controlled trial

Mara Y Roth, Kat Lin, Katrine Bay, John K Amory, Bradley D Anawalt, Alvin M Matsumoto, Brett T Marck, William J Bremner, Stephanie T Page, Mara Y Roth, Kat Lin, Katrine Bay, John K Amory, Bradley D Anawalt, Alvin M Matsumoto, Brett T Marck, William J Bremner, Stephanie T Page

Abstract

Objective: To study the potential role for using serum biomarkers, including insulin-like factor 3 (INSL3), 17α-hydroxyprogesterone, antimüllerian hormone, and inhibin B, as correlates of intratesticular T (IT-T) concentrations in men.

Design: Prospective, randomized, controlled trial.

Setting: University-based medical center.

Patient(s): Thirty-seven healthy men aged 18-50 years.

Intervention(s): All men received the GnRH antagonist acyline, plus very low doses of hCG (0 IU, 15 IU, 60 IU, or 125 IU) SC every other day or 7.5 g T gel daily (75 mg delivered). The IT-T concentrations obtained by percutaneous testicular aspiration with simultaneous serum protein and steroid concentrations were measured at baseline and after 10 days of treatment.

Main outcome measure(s): Intratesticular and serum hormone and gonadotropin concentrations.

Result(s): After 10 days of gonadotropin suppression, serum INSL3 decreased by more than 90% and correlated highly with IT-T concentrations. In contrast, serum inhibin B, antimüllerian hormone, and 17α-hydroxyprogesterone did not correlate with IT-T. Serum INSL3 increased with the dose of hCG administered and returned to baseline after treatment.

Conclusion(s): Serum INSL3 correlates highly with IT-T and serum T concentrations during acute gonadotropin suppression in men. Human chorionic gonadotropin stimulates dose-dependent increases in INSL3 and IT-T in healthy men and might be a useful biomarker of IT-T concentration in some clinical settings.

Clinical trial registration number: NCT# 00839319.

Trial registration: ClinicalTrials.gov NCT00839319.

Copyright © 2013 American Society for Reproductive Medicine. All rights reserved.

Figures

Figure 1
Figure 1
Baseline correlation between serum INSL3 and serum LH for all 31 subjects. The line shown represents the best linear fit.
Figure 2
Figure 2
Box plot of serum INSL3 concentration in gonadotropin-suppressed subjects at baseline (n=31) and on day 10 by treatment group (n=6 for the 0 IU hCG group, n=7 for the 15 IU hCG group, n=5 for the 60 IU hCG group, and 125 IU hCG group). * p

Figure 3

Figure 3A–C. Correlations between post-treatment…

Figure 3

Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG…

Figure 3
Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular testosterone (A), serum testosterone (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit.

Figure 3

Figure 3A–C. Correlations between post-treatment…

Figure 3

Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG…

Figure 3
Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular testosterone (A), serum testosterone (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit.

Figure 3

Figure 3A–C. Correlations between post-treatment…

Figure 3

Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG…

Figure 3
Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular testosterone (A), serum testosterone (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit.
Figure 3
Figure 3
Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular testosterone (A), serum testosterone (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit.
Figure 3
Figure 3
Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular testosterone (A), serum testosterone (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit.
Figure 3
Figure 3
Figure 3A–C. Correlations between post-treatment serum INSL3 for all 23 subjects receiving hCG therapy intratesticular testosterone (A), serum testosterone (B), and serum hCG (C). Dotted lines represent the lower limit of the normal range. Lines shown represent the best linear fit.

Source: PubMed

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