Circulating insulin-like factor 3 (INSL3) in healthy and infertile women

Anand‐Ivell, Ravinder; Tremellen, Kelton; Dai, Yanzhenzi; Heng, Kee; Yoshida, Masashi; Knight, P. G.; Hale, Georgina E.; Ivell, Richard

doi:10.1093/humrep/det349

Cited by 46 publications

(31 citation statements)

References 39 publications

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“…INSL3 has been suggested as a laboratory test that can be used in the diagnosis of PCOS (16,48). However, these studies were conducted with adult women.…”

Section: Discussionmentioning

confidence: 99%

Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results

Yetim

Yetim²,

Baş³

et al. 2016

Jcrpe

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Objective:Polycystic ovary syndrome (PCOS) is a common endocrine problem in adolescents with an increasing prevalence of 30%. Pursuing new biomarkers with high specificity and sensitivity in the diagnosis of PCOS in adolescents is currently an active area of research. We aimed to investigate the diagnostic value of anti-Müllerian hormone (AMH), insulin-like peptide-3 (INSL3), inhibin-A (INH-A), and inhibin-B (INH-B) in adolescents with PCOS and also to determine the association, if any, between these hormones and clinical/laboratory findings related with hyperandrogenism.Methods:The study group comprised 53 adolescent girls aged between 14.5 and 20 years who were admitted to our outpatient clinic with symptoms of hirsutism and/or irregular menses and diagnosed as having PCOS in accordance with the Rotterdam criteria. Twenty-six healthy peers, eumenorrheic for at least two years and body mass index-matched, constituted the controls. Fasting blood samples for hormones [luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone-sulfate (DHEAS), androstenedione (D4-A), total/free testosterone (T/fT), sex hormone binding globulin (SHBG), AMH, INSL3, INH-A, INH-B] were drawn after an overnight fast.Results:In the PCOS group, 83% of the subjects were oligomenorrheic/amenorrheic and 87% had hirsutism. The LH, LH/FSH ratio, total T, fT, free androgen-index (FAI), DHEAS levels were significantly higher (p=0.005, p=0.042, p=0.047, p<0.001, p=0.007, p=0.014, respectively) and SHBG was significantly lower (p=0.004) in PCOS patients as compared to the controls. Although the INSL-3 and INH-B levels showed no difference between the groups (p>0.05), AMH and INH-A levels were found to be significantly higher in the PCOS group compared to the controls (p<0.001, p<0.001, respectively). In multiple linear regression analysis, WC SDS (p=0.028), logD4-A (p=0.033), logSHBG (p=0.031), and total ovarian volume (p=0.045) had significant effects on AMH levels, and LH (p=0.003) on INH-A levels. In receiver-operating characteristic analysis, the cut-off values for AMH and INH-A were 6.1 ng/mL (sensitivity 81.1%) and 12.8 pg/mL (sensitivity 86.8%), respectively, to diagnose PCOS. When AMH and INH-A were used in combination, the sensitivity (96.2%) increased.Conclusion:INSL3 and INH-B were not found to have diagnostic value in adolescents with PCOS. On the other hand, it was shown that INH-A could be used as a new diagnostic biomarker in addition to AMH.

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“…INSL3 has been suggested as a laboratory test that can be used in the diagnosis of PCOS (16,48). However, these studies were conducted with adult women.…”

Section: Discussionmentioning

confidence: 99%

Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results

Yetim

Yetim²,

Baş³

et al. 2016

Jcrpe

View full text Add to dashboard Cite

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“…Free testosterone level (pmol/L) was calculated with the formula serum testosterone (nmol/L) × 10 × [2.28–1.38 × log( SHBG (nmol/L) × 0.1)]. INSL3 was measured using an established and well-validated time-resolved fluorescent immunoassay [27], modified for higher sensitivity [28]. The LOD was 10 pg/mL, with intra- and interplate CVs across the range of measurement of < 3 and < 10%, respectively.…”

Section: Methodsmentioning

confidence: 99%

Testicular Function and Bone in Young Men with Severe Childhood-Onset Obesity

Laakso

Viljakainen²,

Lipsanen‐Nyman

et al. 2018

Horm Res Paediatr

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Background: Previous studies suggest increased risk for hypoandrogenism and fractures in men with obesity. We aimed to describe the effects of severe childhood-onset obesity on the cross talk between metabolic state, testes, and skeleton at late puberty. Methods: A cohort of adolescent and young adult males with severe childhood-onset obesity (n = 21, mean age 18.5 years) and an age-matched control group were assessed for testicular hormones and X-ray absorptiometry-derived bone mass. Results: Current median body mass indexes for the obese and control subjects were 37.4 and 22.9. Severe early-onset obesity manifested with lower free testosterone (median [interquartile range] 244 [194–332] vs. 403 [293–463] pmol/L, p = 0.002). Lower insulin-like 3 (1.02 [0.82–1.23] vs. 1.22 [1.01–1.46] ng/mL, p = 0.045) and lower ratio of testosterone to luteinizing hormone (2.81 [1.96–3.98] vs. 4.10 [3.03–5.83] nmol/IU, p = 0.008) suggested disrupted Leydig cell function. The degree of current obesity inversely correlated with free testosterone (τ = –0.516, p = 0.003), which in turn correlated positively with bone area at all measurement sites in males with childhood-onset obesity. Conclusions: Severe childhood-onset obesity is associated with impaired Leydig cell function in young men and lower free testosterone may contribute to impaired skeletal characteristics.

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“…Studies in cohorts of adult women suggest that INSL3 plasma levels are indicative of the number of ovarian antral follicles recruited and growing within a follicular wave (AnandIvell et al, 2013). As INSL3 is a product of the thecal cells of ovarian follicles, plasma INSL3 levels have been investigated and shown to be elevated in polycystic ovary syndrome, a common female endocrine disorder characterized by excessive production of androgens from ovarian follicles (Gambineri et al, 2007;Szydlarska et al, 2012;Anand-Ivell et al, 2013). Importantly, a recent study in cows demonstrated that INSL3 has a positive autoregulatory role in maintaining thecal androgen production that is essential for normal ovarian follicle development (Glister et al, 2013).…”

mentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

120

118

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Circulating insulin-like factor 3 (INSL3) in healthy and infertile women

Abstract: The present retrospective study was largely supported by departmental funds. There were no competing interests.

Cited by 46 publications

References 39 publications

Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results

Anti-Müllerian Hormone and Inhibin-A, but not Inhibin-B or Insulin-Like Peptide-3, may be Used as Surrogates in the Diagnosis of Polycystic Ovary Syndrome in Adolescents: Preliminary Results

Testicular Function and Bone in Young Men with Severe Childhood-Onset Obesity

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

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