Human Reproduction Update Advance Access originally published online on March 28, 2009
Human Reproduction Update 2009 15(4):463-476; doi:10.1093/humupd/dmp011
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Biology of insulin-like factor 3 in human reproduction
1 School of Molecular and Biomedical Science, Research Centre for Reproductive Health, University of Adelaide, SA 5005, Australia 2 Freemasons Foundation Centre for Men's Health, University of Adelaide, SA 5005, Australia
3 Correspondence address. E-mail: richard.ivell{at}adelaide.edu.au
BACKGROUND: Insulin-like factor 3 (INSL3) is a neohormone that has evolved to address specific mammalian traits, in particular, the first phase of testicular descent towards the scrotum during mid-gestation.
METHODS: A thorough literature search was made in PubMed using the terms INSL3, as well as the older synonyms RLF and Ley-IL.
RESULTS: INSL3 is a major secretory product of the testicular Leydig cells in the fetus and in adult men, and in rodent models, reduction in fetal INSL3 expression is an early marker of the testicular dysgenesis syndrome. In women, it is produced in lower amounts by ovarian theca and luteal cells, and circulating levels are increased in women with polycystic ovarian syndrome. During pregnancy, there is evidence for an interaction regulating the feto-placental unit. The presence of INSL3 in amniocentesis samples taken at 12–14 weeks gestation is absolutely specific for male gender, and levels are predictive of subsequent pre-eclampsia and/or birthweight. INSL3 is also involved in adult traits, such as spermatogenesis and bone metabolism. In adult men, INSL3 is constitutively expressed and secreted into the bloodstream at a constant level, reflecting the number and/or functional capacity of the Leydig cells. In complete contrast, testosterone is highly variable within individuals, is acutely responsive to fluctuations in the hypothalamic–pituitary–gonadal axis and appears to have marginal diagnostic value. INSL3 declines consistently with age in adult men.
CONCLUSIONS: INSL3 promises to become an important new diagnostic tool to characterize those men with late-onset hypogonadism and to add clinical diagnostic value at amniocentesis.
Key words: cryptorchidism / hypogonadism / Leydig cells / feto-placental unit / relaxin-like
Received on January 23, 2009; revised February 24, 2009; accepted on March 1, 2009
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  R. Anand-Ivell, K. Heng, B. Hafen, B. Setchell, and R. Ivell Dynamics of INSL3 Peptide Expression in the Rodent Testis Biol Reprod, September 1, 2009; 81(3): 480 - 487. [Abstract] [Full Text] [PDF]
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