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

Abstract

Objective To study the potential role for using serum biomarkers including insulin-like factor 3 (INSL3), 17-hydroxyprogesterone (17-OHP), anti-Müllerian hormone (AMH) and inhibin B (INHB) as correlates of intratesticular testosterone (IT-T) concentrations in men. Design Prospective, randomized-controlled trial Setting University-based medical center Patients 37 healthy men ages 18–50 Interventions All men received the gonadotropin-releasing hormone antagonist, acyline, plus very low doses of human chorionic gonadotropin (hCG) (0 IU, 15 IU, 60 IU or 125 IU) subcutaneously every other day or 7.5 grams testosterone gel daily (7.5 mg delivered). 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 Measures Intratesticular and serum hormone and gonadotropin concentrations Results Following 10 days of gonadotropin suppression, serum INSL3 decreased by over 90% and correlated highly with IT-T concentrations. In contrast, serum INHB, AMH and 17-OHP did not correlate with IT-T. Serum INSL3 increased with the dose of hCG administered and returned to baseline after treatment. Conclusions Serum INSL3 correlates highly with IT-T and serum testosterone concentrations during acute gonadotropin suppression in men. HCG 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. Clinicaltrials.gov NCT# 00839319

Identification of biochemical differences between different forms of male infertility by nuclear magnetic resonance (NMR) spectroscopy

“…The discovery of noninvasive, highly sensitive and specific biomarkers by NMR spectroscopy would eliminate the need for invasive testing in the infertile man and also allowing an expanded and more specific classification of male factor infertility [19,36]. It is possible that the observed differences in biomarker profiles of patients with different forms of infertility by 1 H-NMR spectroscopy could highlight the presence of clinically relevant information.…”

Serum levels of insulin-like factor 3, anti-Müllerian hormone, inhibin B, and testosterone during pubertal transition in healthy boys: a longitudinal pilot study

“…Several studies have found positive correlations, some significant, between LH and INSL3 concentrations (Foresta et al 2004, Bay et al 2005, Ferlin et al 2006a, Cabrol et al 2011. Furthermore, INSL3 concentrations in serum increase upon long-term stimulation (weeks or months) with human chorionic gonadotropin in gonadotropin-suppressed men, and decrease in response to gonadotropin suppression, further supporting the chronic regulation of INSL3 by LH , Roth et al 2013.…”

“…In rodent gametes, RXFP2 may also couple to the inhibitory G-protein (Kawamura et al 2004, Hutson 2013. The expression of INSL3 is believed to be regulated by luteinizing hormone (LH; Foresta et al 2004, Ferlin et al 2006a, Cabrol et al 2011, Roth et al 2013 in a chronic, cell differentiationrelated manner rather than the acute regulation that LH exerts on testosterone (Bay et al 2005, Anand-Ivell et al 2006a, Bay & Andersson 2011. Both gene expression and protein secretion studies in rodents show that INSL3 reflects a relatively mature Leydig cell phenotype .…”

Relationships between Anti-mullerian Hormone, Testosterone, Luteinizing Hormone and Follicle Stimulating Hormone in Men on Testosterone Therapy

“…Roth et al [28] also reported that acute gonadotrophin suppression (over 10 days) resulted in reduced serum testosterone and IT-T and noted that although AMH might be expected to rise in this setting, it did not. They queried whether the AMH assay was reliable and considered whether the lack of FSH stimulation may have also contributed to a lack of AMH rise.…”

“…When LH is suppressed, IT-T levels are similarly reduced dramatically [27,28]. Exogenous testosterone therapy has been shown to reduce IT-T to ~2% of control levels by means of LH and FSH suppression [17].…”