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Endocrine Abstracts (2021) 77 SE1.3 | DOI: 10.1530/endoabs.77.SE1.3

SFEBES2021 Senior Endocrinologists’ Session (1) (3 abstracts)

INSL3: a new index of testis function in puberty and aging

Richard Ivell & Ravinder Anand-Ivell


University of Nottingham, Sutton Bonington, UK.


Insulin-like peptide 3 (INSL3) is a peptide hormone secreted exclusively in boys and men by the mature Leydig cells of the testes. It acts through a unique G-protein-coupled receptor, called RXFP2. In the female INSL3 regulates ovarian antral follicle growth. Whereas INSL3 in the male foetus is responsible for the first phase of testicular descent, in the adult it appears to support spermatogenesis and bone health. Importantly, it is expressed constitutively, is independent of acute regulation by the HPG axis, and effectively measures the product of Leydig cell numbers and their differentiation status, i.e. the functional capacity of Leydig cells to make testosterone, correlating with the T/LH ratio. We have developed very specific time-resolved fluorescence immunoassays and show that INSL3 has low within-individual and technical variance. In humans, rodents, and bulls, as a mature Leydig cell biomarker, INSL3 effectively monitors the dynamics of puberty, acting much like a biochemical Tanner scale, without any of the fluctuation seen with testosterone, to achieve a stable final level in early adulthood. This adult peak varies up to 10-fold in the normal human population, reflecting a wide range of Leydig cell functional capacity. The causes of this variance are unknown, though we have shown that it may in part depend on childhood BMI, early nutrition, and possible maternal impacts. Studies in large aging male cohorts indicate that INSL3 declines consistently at 15% per decade from age 40 and measures the decline of testis function independently of compensation by the HPG axis. The 10-fold range of INSL3 in young men persists as men age, suggesting that low INSL3 in young adulthood will predict low INSL3, hypogonadism, and related morbidity in older age.

Volume 77

Society for Endocrinology BES 2021

Edinburgh, United Kingdom
08 Nov 2021 - 10 Nov 2021

Society for Endocrinology 

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