AMH and INSL3 in testicular and extragonadal pathophysiology: what do we know?

Abstract

Background: It is commonly accepted that testicular function is prevalently regulated by the hypothalamic–pituitary–gonadal axis: The pulsatile secretion of GnRH by the hypothalamus induces pituitary expression of the two gonadotropins FSH and LH, which then stimulate Sertoli and Leydig cells, respectively, therefore regulating steroidogenesis and spermatogenesis. However, a growing body of evidence has recently suggested that other hormones act on the reproductive tract since the early phases of fetal development. Anti-Müllerian hormone and INSL3 are still largely used only for research purposes despite being increasingly recognized as markers of Sertoli and Leydig cells function, respectively. Objectives: Provide an up-to-date review of the role of anti-Müllerian hormone and INSL3 in human pathophysiology according to current evidence. Materials and Methods: A thorough literature review was performed on PubMed, OVID MEDLINE/EMBASE and Google Scholar for papers concerning anti-Müllerian hormone and INSL3 in human males. Results: INSL3 is not acutely regulated by the hypothalamic–pituitary axis but is constitutively secreted by Leydig cells, therefore representing a valid marker for their number and status. Anti-Müllerian hormone expression, on the other hand, is downregulated by androgens, therefore occurring mostly at the early stages of testicular differentiation and before the onset of puberty. Several conditions affecting testicular development, such as male hypogonadotropic hypogonadism, and their treatment have been associated to specific pattern of INSL3 and anti-Müllerian hormone expression, proving a role for both hormones in the diagnostic and therapeutic management. Recent reports suggest a role for both anti-Müllerian hormone and INSL3 in extra gonadal physiology, such as cardiovascular and bone health. Conclusion: Anti-Müllerian hormone and INSL3 are markers of Sertoli and Leydig cells maturation, respectively, usually involved in the pathogenesis of disorders of sexual differentiation. However, their role in testicular pathology has only been hinted at in the last decades. Recent evidence supports an involvement of both anti-Müllerian hormone and INSL3 in extragonadal pathophysiology as well.