Defining the end of puberty in boys: INSL3 and the acute determinants of adult Leydig cell functional capacity

Bilal TulumcuRichard IvellWaleed AlhujailiRavinder Anand-Ivell^*

• University of Nottingham, Nottingham, United Kingdom

The Leydig cells of the testes make most of the testosterone suppor ng male physiology across the lifespan. While measuring testosterone itself is subject to high technical and biological variance, this func onal capacity to make testosterone is be er assessed by measuring another Leydig cell hormone, insulin-like pep de 3 (INSL3). This is highly consistent within a man, though shows high between-individual variance correla ng with age-related morbidity. We do not know why INSL3 is reduced in some men, leading to hypogonadism and morbidity, except that this variance appears to originate during childhood and adolescence. The Leydig cell popula on develops during puberty with INSL3 levels ac ng as a biochemical equivalent to Tanner staging. Using the ALSPAC cohort, we have measured INSL3 at 17 and 24 years, assessing its cross-sec onal rela onship to other contemporary parameters; it a ains a maximum at approximately 22 years, marking the true end of puberty, before se ling to a lower adult level by 24 years. Other than correla ng with contemporary BMI and smoking status, INSL3 at 24 years appears to be stable, independent of other factors, and largely determined by INSL3 levels at 17 years or earlier, emphasizing the importance of childhood and pubertal factors in establishing adult Leydig cell func onal capacity.