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Insulin-like factor 3 and the HPG axis in the male

Ivell, Richard; Heng, Kee; Anand-Ivell, Ravinder


Richard Ivell

Kee Heng


The hypothalamic–pituitary–gonadal (HPG) axis comprises pulsatile GnRH from the hypothalamus impacting on the anterior pituitary to induce expression and release of both LH and FSH into the circulation. These in turn stimulate receptors on testicular Leydig and Sertoli cells, respectively, to promote steroidogenesis and spermatogenesis. Both Leydig and Sertoli cells exhibit negative feedback to the pituitary and/or hypothalamus via their products testosterone and inhibin B, respectively, thereby allowing tight regulation of the HPG axis. In particular, LH exerts both acute control on Leydig cells by influencing steroidogenic enzyme activity, as well as chronic control by impacting on Leydig cell differentiation and gene expression. Insulin-like peptide 3 (INSL3) represents an additional and different endpoint of the HPG axis. This Leydig cell hormone interacts with specific receptors, called RXFP2, on Leydig cells themselves to modulate steroidogenesis, and on male germ cells, probably to synergize with androgen-dependent Sertoli cell products to support spermatogenesis. Unlike testosterone, INSL3 is not acutely regulated by the HPG axis, but is a constitutive product of Leydig cells, which reflects their number and/or differentiation status and their ability therefore to produce various factors including steroids, together this is referred to as Leydig cell functional capacity. Because INSL3 is not subject to the acute episodic fluctuations inherent in the HPG axis itself, it serves as an excellent marker for Leydig cell differentiation and functional capacity, as in puberty, or in monitoring the treatment of hypogonadal patients, and at the same time buffering the HPG output.


Ivell, R., Heng, K., & Anand-Ivell, R. (in press). Insulin-like factor 3 and the HPG axis in the male. Frontiers in Endocrinology, 5(6),

Journal Article Type Article
Acceptance Date Jan 13, 2014
Online Publication Date Jan 27, 2014
Deposit Date Mar 22, 2017
Publicly Available Date Mar 22, 2017
Journal Frontiers in Endocrinology
Electronic ISSN 1664-2392
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 5
Issue 6
Keywords INSL3, RXFP2, Leydig cell, testosterone, puberty, hypothalamic hypogonadism
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Copyright Statement Copyright information regarding this work can be found at the following address:


fendo-05-00006.pdf (1.5 Mb)

Copyright Statement
Copyright information regarding this work can be found at the following address:

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