Relaxin and Related Peptides in Male Reproduction

Abstract

The relaxin hormone is renowned for its function in pregnancy, parturition and other aspects of female reproduction. At the same time, the role of relaxin in male reproduction is still debated. Relaxin is prominently expressed in prostate and its receptors are found in several male reproductive organs; however, the data indicative of its contribution to differentiation and functioning of prostate or testis are contradictory. Prostate relaxin is a main source of this peptide in the seminal plasma. The relaxin effects on sperm motility and fertilization have been reported. The expression of other relaxin related peptides, such as INSL5 and INSL6 was described in testis; yet, currently there are no experimental data to pinpoint their biological functions. The other member of relaxin peptide family, insulin-like 3 peptide (INSL3), is a major player in male development. The INSL3 peptide is expressed in testicular fetal and adult Leydig cells and is directly responsible for the process of abdominal testicular descent (migration of the testes towards the scrotum during male development). Genetic targeting of the Insl3 gene or INSL3 GPCR receptor Lgr8/Rxfp2 causes high intra-abdominal cryptorchidism due to a differentiation failure of testicular ligaments, the gubernacula. Several mutations of these two genes rendering nonfunctional proteins have been described in human patients with testicular maldescent. Thus, in this chapter we review the data related to the expression and function of relaxin and related peptides in male reproduction.

What is new in cryptorchidism and hypospadias—a critical review on the testicular dysgenesis hypothesis

“…The primary hormone-regulating transabdominal descent is thought to be INSL3 [46]. Insulin-like hormone 3, also known as relaxin-like factor, is a member of the insulin-like hormone superfamily [47]. It is secreted by the Leydig cells shortly after the onset of testicular development and controls the swelling reaction of the gubernaculum [48].…”

Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis

“…The identification of novel endogenous factors involved in the proliferation, viability, and migration of prostate cancer cells may create potential therapeutic targets for future treatment. The prostate is one of the main sites of relaxin (RLN) expression in males (Agoulnik 2007). Originally, this peptide hormone was identified by its effects on the relaxation (hence the name) of pubic symphysis, cervical softening, and the inhibition of spontaneous myometrial contractions during pregnancy and parturition in females (Sherwood 2004).…”

Immunolocalization of INSL3 in dog foetal Leydig cells and the LGR8 receptor in the gubernaculum testis

“…Insulin-like 3 (INSL3), a peptide belonging to the insulin-relaxin family and also known as Leydig cell-derived insulin-like factor, appears to play a prominent role in male sexual development and is considered to be fundamental for the descent of the testis (Agoulnik 2007). A direct influence of Müllerian inhibiting substance/anti-Müllerian hormone (AMH or MIS) upon the growth of the gubernaculum has also been supposed (Kubota et al 2002).…”