Insulin-like 3

Also known as: Leydig insulin-like peptide, Relaxin-like factor, INSL3, P51460

**Mechanism of Action** Insulin-like 3 (INSL3), also known as Leydig insulin-like peptide or relaxin-like factor, is a member of the insulin/relaxin superfamily primarily secreted by testicular Leydig cells. It exerts its effects by binding to the relaxin family peptide receptor 2 (RXFP2), a G-protein-coupled receptor. Activation of RXFP2 triggers downstream signaling pathways, including cAMP accumulation and MAPK/ERK activation, which mediate cellular responses. INSL3 is critical for testicular descent during fetal development, acting via the gubernaculum to facilitate transabdominal migration of the testes. In adults, it is implicated in paracrine regulation of testicular function, including modulation of germ cell survival and steroidogenesis. **Key Research Findings** Preclinical studies demonstrate that INSL3 knockout mice exhibit bilateral cryptorchidism and impaired spermatogenesis, confirming its essential role in testicular descent. In humans, mutations in the *INSL3* or *RXFP2* genes are associated with cryptorchidism, a common congenital anomaly. Experimental research also suggests INSL3 may influence bone metabolism, as RXFP2 is expressed in osteoblasts, and INSL3-deficient mice show reduced bone mass. Additionally, circulating INSL3 levels correlate with Leydig cell function and decline with age, making it a potential biomarker for male reproductive aging. However, its therapeutic applications remain experimental, with no approved clinical uses. **Clinical Relevance** INSL3 has potential diagnostic value for assessing Leydig cell function in conditions such as hypogonadism, cryptorchidism, and infertility. Experimental studies are exploring its role in bone health and as a target for male contraceptive development. However, clinical translation is limited by the need for further validation of its systemic effects and safety profile. Current evidence is derived from animal models and small human studies, with no established therapeutic indications. For research purposes only — not medical advice.

Key data

Mechanism of action

Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor

Research & studies

Frequently asked questions

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