Relaxin family peptides in the male reproductive system--a critical appraisal

Abstract

The human genome project has identified, besides ovarian relaxin (RLN), six other relaxin-like molecules (RLN3, H1-RLN, INSL3-6), most of which appear to be expressed in the testis and/or male reproductive system, together with four different G-protein-coupled receptors responsive to one or other of these peptides. Earlier work on relaxin in the male assumed the simplistic hypothesis of only a single relaxin-like entity. This review systematically examines the expression and physiology of relaxin-like molecules in the male reproductive system in order to reappraise the importance of this hormone system for male reproductive function. Although there are important species differences, only INSL3 and INSL6 appear to be generally expressed at a moderately high level within the testis, whereas ovarian RLN is consistently a major secretory product of the prostate epithelium. However, all members of this relaxin-like family appear to be expressed also at a low level in different organs of the male reproductive system, suggesting possible autocrine/paracrine effects. The four receptors (RXFP1-4) for these peptides are also expressed to differing levels in both somatic and seminiferous compartments of the testis and in the prostate, supporting relevant functions for most members of this interesting peptide family. Recent studies of relaxin family peptides in prostate pathology highlight their functional importance in the clinical context as potential causative, diagnostic and therapeutic agents and warrant more specific and detailed studies of their roles also in regard to male fertility and other aspects of male reproductive function.

Hydroxysteroid Dehydrogenases – Localization, Function and Regulation in the Testis

“…Our own studies in bank voles have revealed that insulin like growth factor I (IGF-I) stimulates whereas IL-1 and interleukin 1 (IL-1 ) inhibit testis steroidogenic and spermatogenic function in sexually active males (Gancarczyk et al, 2006;Kmicikiewicz & Bilinska, 1997;Kmicikiewicz et al, 1999). Interesting results have been recently reported by Ivell et al (2011) who demonstrated that 17 -HSD 10 mRNA expression in mice testis is regulated by locally produced relaxin (RLN) dependently of animal age.…”

Regulation of the reproductive cycle and early pregnancy by relaxin family peptides

“…INSL4 is made in large amounts by the syncytiotrophoblast and maternal decidua (Laurent et al, 1998;Millar et al, 2005), and experiments on amniotic epithelial cells suggest that unlike relaxin it has a pro-apoptotic role (Millar et al, 2005), a view which is strengthened by its increased expression in placentae of growth-restricted fetuses (Millar et al, 2005). INSL6 is also a paralogue of relaxin and in the male is expressed in substantial amounts by meiotic and post-meiotic germ cells (Lok et al, 2000;Ivell et al, 2011). Indeed a recent INSL6-knockout mouse shows a marked male infertility phenotype (Burnicka-Turek et al, 2009).…”

“…The role of these peptide hormones in later pregnancy, in lactation and in male reproductive function have been recently covered in other reviews (e.g. Bathgate et al, 2006;Parry and Vodstrcil, 2007;Ivell et al, 2011) and will not be further discussed here.…”

Relaxin 2 – a pregnancy hormone involved in the process of carcinogenesis

“…Domena B, posiadająca specyficzny motyw wiążący (Arg-X-X-X-Arg-X-X-Ile/Val), odpowiada za interakcje z receptorami relaksynowymi. Warto podkreślić, że relaksyna 2 w postaci funkcjonalnego białka nie oddziaływuje z receptorami insulinowymi i wykazują odmienne właściwości biologiczne [2][3][4][5][6][7][8][9][10][11].…”

“…Powoduje to wzrostu śródkomórkowego poziomu cAMP i pobudzenie ścieżki sygnałowej dla rodziny kinazy białkowej A (PKA; ang. protein kinase A) oraz wpływa na produkcję tlenku azotu [3][4][5][6][7][8][9][10][11].…”