Reproduction Abstracts

Anti-Mullerian hormone (AMH) is a testicular Sertoli cell product belonging to the TGF-beta superfamily responsible for regression of the Mullerian ducts in the male foetus. It plays a pivotal role in sexual differentiation of the internal genital ducts. The existence of AMH was first postulated by Alfred Jost in the 1950s and was long considered to be a foetal testis-specific factor. However, it has since emerged that AMH and its receptors are also expressed by the post-natal ovary and play important roles in the negative regulation of preantral follicle development and FSH-induced steroidogenesis at later follicle stages. In a clinical context, circulating AMH levels are closely linked to antral follicle count estimated by ultrasonography and serum AMH levels are increasingly used as a proxy for ‘ovarian reserve’ in patients undergoing fertility evaluation/treatment. Another factor first identified in the foetal testis, insulin-like peptide 3 (INSL3), has long been recognised for its role in the trans-abdominal phase of testicular descent. INSL3 secreted by Leydig cells promotes development of the caudal genital ligament (gubernaculum) that fixes the testis to the inguinal region, while androgen inhibits development of the cranial suspensory ligament that would otherwise retain the gonad in a cranial position close to the kidney. Knockout of INSL3 or its receptor (RXFP2) in mice results in cryptorchidism with the testis remaining in an ovary-like position. More recently, INSL3/RXFP2 signaling has been implicated in regulation of ovarian function, with theca cells being a main site of expression. INSL3 signalling appears to modulate ovarian androgen production since knockdown of either INSL3 or its receptor (RXFP2) in bovine theca cells inhibits androgen biosynthesis while exogenous INSL3 can raise androgen secretion. The inhibitory action of bone morphogenetic proteins on thecal androgen production may be mediated by reduced INSL3-RXFP2 signalling. Moreover, circulating INSL3 (and AMH) levels are raised in women with polycystic ovarian syndrome reinforcing a positive association with ovarian androgen production. These aspects of AMH and INSL3 action will be discussed in this presentation.