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

Fertil Steril. 2013 Jan;99(1):132-139. doi: 10.1016/j.fertnstert.2012.09.009. Epub 2012 Oct 3.


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: NCT00839319.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 17-alpha-Hydroxyprogesterone / blood
  • Adolescent
  • Adult
  • Anti-Mullerian Hormone / blood
  • Biomarkers / blood
  • Chorionic Gonadotropin / pharmacology*
  • Dose-Response Relationship, Drug
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Gonadotropins / deficiency*
  • Humans
  • Inhibins / blood
  • Insulin / blood*
  • Male
  • Middle Aged
  • Oligopeptides / pharmacology
  • Proteins
  • Testis / drug effects*
  • Testis / metabolism*
  • Testosterone / metabolism*
  • Young Adult


  • Biomarkers
  • Chorionic Gonadotropin
  • Gonadotropins
  • Insulin
  • Leydig insulin-like protein
  • Oligopeptides
  • Proteins
  • inhibin B
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Inhibins
  • 17-alpha-Hydroxyprogesterone
  • Anti-Mullerian Hormone
  • acyline

Associated data