Relaxin Is a Key Mediator of Prostate Growth and Male Reproductive Tract Development

Abstract

SUMMARY:Male mice deficient in relaxin showed retarded growth and marked deficiencies in the reproductive tract within 1 month of age. At 3 months of age, male reproductive organ weight (including the testis, epididymis, prostate, and seminal vesicle) from relaxin null (RLXϪ/Ϫ) mice were significantly (p Ͻ 0.05) smaller than those of wild-type (RLXϩ/ϩ) male mice. Histologic examination of RLXϪ/Ϫ mouse tissues demonstrated decreased sperm maturation (testis), increased collagen, and decreased epithelial proliferation in the prostate compared with tissues obtained from RLXϩ/ϩ animals. The degree of sperm maturation in the testes of sexually mature RLXϪ/Ϫ mice (3 months) resembled that of immature (1 month) RLXϩ/ϩ mice and correlated with a decrease in fertility in RLXϪ/Ϫ mice. The marked differences in the extracellular matrix of the testis and prostate in RLXϪ/Ϫ males also correlated with an increase in the rate of cell apoptosis. Relaxin and LGR7 (relaxin receptor) mRNA expression was demonstrated in the prostate gland and testis of the normal mouse. Data from this study demonstrate that relaxin is an important factor in the development and function of the male reproductive tract in mice and has an essential role in the growth of the prostate and maintenance of male fertility. Relaxin may mediate its effects on growth and development by serving as an antiapoptotic factor. (Lab Invest 2003, 83:1055-1067.

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“…They also showed a decreased epithelial proliferation in the prostate and decreased sperm maturation [14]. These studies suggested that relaxin lack could produce local fibrosis in the prostate gland and in testes, but the following study by Ganesan et al [15] do not observe the same results.…”

“…Deficiency of relaxin in males remains controversial: Samuel et al [14] studied Rln -/-male mice and wild-type Rln +/+ and found a decrease in prostate, testis epididymis and seminal vesicles weight in Rln -/-mice. They also showed a decreased epithelial proliferation in the prostate and decreased sperm maturation [14].…”

H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis

“…First, considering that the murine M1 relaxin peptide is a hormone critical for mouse prostate growth and development, 17 it is possible that the high H2 relaxin levels in the PC3-Luc-H2/eGFP-derived tumors may trigger in vivo prostate growth mimicking that which occurs during early development. Second, the high H2 relaxin levels in PC3-Luc-H2/eGFP cell-derived tumors may indirectly stimulate the formation of tumor vasculature thereby providing a platform for enhanced tumor cell growth through the upregulation of effectors such as VEGF and NOS, for example.…”

“…17 Male mice deficient for murine M1 relaxin (equivalent is H2 relaxin) exhibit retarded growth and marked deficiencies in the reproductive tract, including the testis, epididymis, prostate and seminal vesicles. 17 In the human, relaxin has also been found to be consistently secreted into seminal fluid at levels of 50 ng/mL, which has been correlated with enhancing the capacity for sperm motility. 18 Recently, the relaxin receptor (LGR7) was cloned and found to be coexpressed with H1/H2 relaxins in the prostate.…”

“…12,16 The role of relaxin in the male may be implicated in prostatic growth and fertility. 17 Male mice deficient for murine M1 relaxin (equivalent is H2 relaxin) exhibit retarded growth and marked deficiencies in the reproductive tract, including the testis, epididymis, prostate and seminal vesicles. 17 In the human, relaxin has also been found to be consistently secreted into seminal fluid at levels of 50 ng/mL, which has been correlated with enhancing the capacity for sperm motility.…”