Biological role and clinical significance of insulin-like peptide 3

Insulin-like peptide 3 (INSL3) is the subject of a fast expanding literature reflecting increasing clinical application, particularly as a diagnostic parameter. This review summarizes the recent INSL3 literature published within the last 12-18 months.

Significant inroads have been made to understand how INSL3 is working in testicular descent. It also has other functions in the adult, for example in bone metabolism, extending its role as a largely gender-specific hormone. Advances in molecular pharmacology have increased our understanding of INSL3 interaction with its specific receptor, RXFP2, and delivered new high-affinity antagonists. INSL3 is increasingly being used to assess Leydig cell functional capacity within the testis, independently of factors affecting the hypothalamic-pituitary-gonadal axis, being a robust parameter by comparison with testosterone. Particularly in the aging male, metabolic syndrome, and the effects of adiposity on testis function, INSL3 is a valuable adjunct to the standard clinical repertoire.

The Leydig cell hormone INSL3 is responsible for the first phase of testicular descent during pregnancy and may have multiple roles as a gender-specific circulating hormone in the adult reflecting Leydig cell functional capacity. In women, INSL3 is a paracrine factor within the ovary and probably placenta, in which it may have a fetal gender-specific role.