Insulin-like factor 3 and the HPG axis in the male
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 promot...
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Frontiers
2014
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| Online Access: | https://eprints.nottingham.ac.uk/41437/ |
| _version_ | 1848796272758095872 |
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| author | Ivell, Richard Heng, Kee Anand-Ivell, Ravinder |
| author_facet | Ivell, Richard Heng, Kee Anand-Ivell, Ravinder |
| author_sort | Ivell, Richard |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:45:21Z |
| format | Article |
| id | nottingham-41437 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:45:21Z |
| publishDate | 2014 |
| publisher | Frontiers |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-414372020-05-04T16:41:15Z https://eprints.nottingham.ac.uk/41437/ Insulin-like factor 3 and the HPG axis in the male Ivell, Richard Heng, Kee Anand-Ivell, Ravinder 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. Frontiers 2014-01-27 Article PeerReviewed Ivell, Richard, Heng, Kee and Anand-Ivell, Ravinder (2014) Insulin-like factor 3 and the HPG axis in the male. Frontiers in Endocrinology, 5 (6). pp. 1-7. ISSN 1664-2392 INSL3 RXFP2 Leydig cell testosterone puberty hypothalamic hypogonadism http://journal.frontiersin.org/article/10.3389/fendo.2014.00006/full#h11 doi:10.3389/fendo.2014.00006 doi:10.3389/fendo.2014.00006 |
| spellingShingle | INSL3 RXFP2 Leydig cell testosterone puberty hypothalamic hypogonadism Ivell, Richard Heng, Kee Anand-Ivell, Ravinder Insulin-like factor 3 and the HPG axis in the male |
| title | Insulin-like factor 3 and the HPG axis in the male |
| title_full | Insulin-like factor 3 and the HPG axis in the male |
| title_fullStr | Insulin-like factor 3 and the HPG axis in the male |
| title_full_unstemmed | Insulin-like factor 3 and the HPG axis in the male |
| title_short | Insulin-like factor 3 and the HPG axis in the male |
| title_sort | insulin-like factor 3 and the hpg axis in the male |
| topic | INSL3 RXFP2 Leydig cell testosterone puberty hypothalamic hypogonadism |
| url | https://eprints.nottingham.ac.uk/41437/ https://eprints.nottingham.ac.uk/41437/ https://eprints.nottingham.ac.uk/41437/ |