Insulin-Like Factor 3 Serum Levels in 135 Normal Men and 85 Men with Testicular Disorders: Relationship to the Luteinizing Hormone-Testosterone Axis

Bay, Katrine; Hartung, Stefan; Ivell, Richard; Schumacher, M.; Jürgensen, D.; Jørgensen, Niels; Holm, Magnus; Skakkebæk, Niels E.; Andersson, Anna‐Maria

doi:10.1210/jc.2004-2257

Cited by 169 publications

(203 citation statements)

References 29 publications

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“…In fact, with the establishment of a functional hypothalamic-pituitarygonadal (HPG) axis during puberty, boar Leydig cells appear to be most responsive to LH at puberty as characterized by a dramatic increase in cell number, cell volume, LH receptor number, and intracellular organelles of the Leydig cells (Peyrat et al 1981, Lunstra et al 1986, Franca et al 2000, and also as indicated by our findings that the testosterone levels increased progressively toward puberty with an irregular fluctuation at subsequent ages, whereas E 2 levels increased in a stepwise fashion with advancing age, consistent with previous reports (FlorCruz & Lapwood 1978, Allrich et al 1982, Schwarzenberger et al 1993, Estienne et al 2000. In addition, in other species, INSL3 has been reported to be constitutively expressed and secreted by the Leydig cells under the long-term effects of LH/hCG and is not acutely regulated by LH/hCG and other hormones influencing Leydig cell differentiation, such as insulin-like growth factor1 (IGH1) (Foresta et al 2004, Bay et al 2005, Sadeghian et al 2005. In line with the lack of an acute stimulatory effect of LH, we did not find any correlation between LH and INSL3 in boars, although there are conflicting findings showing a positive correlation between them in normal men (Foresta et al 2004, Ferlin et al 2006.…”

Section: Discussionsupporting

confidence: 89%

Dynamics of insulin-like factor 3 and its receptor expression in boar testes

Minagawa¹,

Sagata²,

Pitia³

et al. 2014

Journal of Endocrinology

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Relaxin-like factor (RLF), now mainly known as insulin-like factor 3 (INSL3), is essential for testis descent during fetal development; however, its function in the adult testis is still being elucidated. As a major step toward understanding the as-yet-unknown function of INSL3 in boars, this study aimed to develop a time-resolved fluoroimmunoassay for boar INSL3, characterize the dynamics of INSL3 expression during development, and demonstrate the expression of the INSL3 hormone-receptor system in the testis. All samples were collected from Duroc boars. The sensitivity of the assay system established was 8.2 pg/well (164 pg/ml), and no cross-reactivity with other hormones, such as porcine relaxin, was observed. Circulating INSL3 was shown to increase progressively during development. INSL3 secreted from the Leydig cells was released not only into the blood circulation but also into the interstitial and seminiferous compartments in sufficient concentrations. A testicular fractionation study revealed that its receptor RXFP2 transcripts were expressed mainly in testicular germ cells. In addition, INSL3 bound to the germ cell membranes in a hormone-specific and saturable manner. These results reveal that INSL3 secreted into the interstitial compartment from the Leydig cells is transported into the seminiferous compartments, where its receptor RXFP2 is expressed mainly in the germ cells to which INSL3 binds, suggesting that INSL3 functions as a paracrine factor on seminiferous germ cells.

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Section: Discussionsupporting

confidence: 89%

Dynamics of insulin-like factor 3 and its receptor expression in boar testes

Minagawa¹,

Sagata²,

Pitia³

et al. 2014

Journal of Endocrinology

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“…The serum concentration of testosterone is most often in the lower half of the reference range of healthy males, and rarely below the reference range. Inhibin B is below the detection limit in the vast majority of KS adults reflecting the absent spermatogenesis (39), whereas the circulating concentrations of AMH and INSL3 are significantly reduced compared with healthy males (40,45,46). Mean testes volume in KS adults is 3.0 ml (range 1.0-7.0) as compared with 22 ml in healthy adult males (Fig.…”

Section: Testicular Endocrinologymentioning

confidence: 92%

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

Aksglæde

Juul

2013

European Journal of Endocrinology

170

114

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Klinefelter syndrome, 47,XXY (KS), is the most frequent sex chromosome aberration in males, affecting 1 in 660 newborn boys. The syndrome is characterized by testicular destruction with extensive fibrosis and hyalinization of the seminiferous tubules resulting in small testes, hypergonadotropic hypogonadism, and azoospermia in the majority of cases. Until recently, infertility was considered an untreatable condition in KS. However, with the development of new advanced assisted reproductive techniques such as testicular sperm extraction (TESE) combined with ICSI it seems that KS patients should no longer be labelled as infertile. Especially, microdissection (micro)-TESE has proved to be an advantageous procedure for the identification of testicular spermatozoa in KS. The aim of this review was to describe current knowledge on the testicular changes occurring in KS, the associated changes in reproductive hormones and spermatogenesis, and the existing possibilities of biological fatherhood in 47,XXY patients. European Journal of Endocrinology 168 R67-R76

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“…INSL3 is a circulating peptide that can be measured by standard immunoassay (26). Levels are increased at puberty and adulthood while they are undetectable in females.…”

Section: Transabdominal Phasementioning

confidence: 99%

Factors controlling testis descent

Hughes¹,

Acerini²

2008

European Journal of Endocrinology

139

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Descent of the testis from an intra-abdominal site in foetal life to an extracorporeal location after birth is a mandatory developmental process to ensure that the mature testis promotes normal spermatogenesis. The two phases of transabdominal and inguinoscrotal descent occur approximately during the first and last thirds of gestation respectively. Key anatomical events to release the testis from its urogenital ridge location and to guide the free gonad into the scrotum are the degeneration of the cranio-suspensory ligament and a thickening of the gubernaculum. Androgens play a role in both these processes, particularly with respect to enabling the testis to traverse the inguinal canal in the final phase of descent. Experiments in animals suggest that androgens mediate this effect via the release of calcitonin gene-related peptide by the genitofemoral nerve, but direct evidence for such a mechanism is lacking in humans. The transabdominal phase of descent is under the control of insulinlike 3 (INSL3), a product of the Leydig cells. Definitive evidence of its role in rodent testis descent is illustrated by the phenotype of bilateral cryptorchidism in Insl3K/K null mice. Circulating levels of INSL3 are higher in boys at puberty, are undetectable in girls and are lower in boys with undescended testes. A minority also have a mutation either in the INSL3 gene or affecting its receptor gene, relaxin/insulin-like family peptide receptor 2 (LGRF8). Other factors that may play a role in testis descent include the anti-Mullerian hormone and members of the HOX gene family. Evidence that the prevalence of undescended testis may be increasing provides a phenotypic readout for the effects of postulated chemicals in the environment interfering in some way with the action of factors that control testis descent. Epidemiological studies point to profound geographical variations in prevalence in countries such as Denmark and Finland. Associations have been found with levels of chemicals labelled as endocrine disruptors being higher in breast milk samples from mothers with cryptorchid boys when compared with controls. The adverse effects of these compounds (e.g. bisphenol A) can be replicated in the offspring of dams exposed during pregnancy. A sensitive marker of an anti-androgen effect of a compound is a reduction in the anogenital distance, an anthropometric measurement that is significantly greater in males compared with females. The observation of an association between the anogenital distance in infant boys and the level of pesticides in the urine of their mothers in late gestation indicates that this has the potential to be a useful surrogate marker of the effects of environmental chemicals on testis descent in human population studies. The rightful place for the testis at birth is in the scrotum in order to provide the temperature differential essential for normal spermatogenesis. Appropriate screening programmes and early surgical intervention are the prerequisites to ensure optimal fertility in adulthood and a con...

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Insulin-Like Factor 3 Serum Levels in 135 Normal Men and 85 Men with Testicular Disorders: Relationship to the Luteinizing Hormone-Testosterone Axis

Cited by 169 publications

References 29 publications

Dynamics of insulin-like factor 3 and its receptor expression in boar testes

Dynamics of insulin-like factor 3 and its receptor expression in boar testes

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

Factors controlling testis descent

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