Effects of acute hCG stimulation on serum INSL3 and 25‐OH vitamin D in Klinefelter syndrome

Abstract

Background It has recently been suggested that the hypergonadotropic hypogonadism characterizing Klinefelter syndrome (KS) might not be due to a steroidogenic dysfunction per se, but mainly to an altered testosterone (T) secretion into the bloodstream. However, the Leydig cell functionality remains incompletely studied in KS, and new markers should be considered. Previous data indicated that chronic hCG stimulation influences the production of both insulin‐like peptide 3 (INSL3) and 25‐hydroxy‐vitamin D (25‐VD) in eugonadal men. Aim of the study To evaluate INSL3 and 25‐VD serum levels, as markers of Leydig cell functionality, in association with sex steroids, after an acute hCG test in a group of KS patients and healthy volunteers. Methods A retrospective analysis of a prospective case‐control clinical trial was carried out. KS patients (n = 11) and age‐matched healthy controls (n = 11) provided a basal blood sample (V0) immediately followed by a single intramuscular injection of hCG 5000 IU. Blood samples were taken in the following five days (V1‐V5). Results At baseline, INSL3 was lower in KS patients compared with controls (P = .007). When adjusted for INSL3 levels, the production of steroids was similar between KS patients and controls. 25‐VD was in the insufficient range both in KS patients and in controls and was not different (P = .064). Acute hCG stimulation increased neither INSL3 nor 25‐VD in both KS patients and controls. In controls, an inverse correlation was detected between INSL3 levels and body mass index (P = .020) and waist circumference (P = .020). Conclusions INSL3 secretion is independent from steroidogenesis, and its production is mostly not influenced by acute hCG stimulation both in KS men and in controls. INSL3 serum levels should be considered as a marker of Leydig cell differentiation and numbers rather than steroidogenesis. 25‐VD serum levels are also not increased by a single acute hCG administration, which was not able to restore the normal concentrations of 25‐VD.

Serum Concentrations and Gonadal Expression of INSL3 in Eighteen Males With 45,X/46,XY Mosaicism

“…Likewise, azoospermia rates were high as reflected in the high FSH/low inhibin B concentrations. This is in line with previous studies on 45,X/46,XY patients, reporting high degrees of external genital androgenization at birth in some patients (13,16,34), high rates of spontaneous puberty, some patients not in need of testosterone treatment (12)(13)(14)(15)(16), but frequent infertility (12,17,(23)(24)(25). In this study, there was no observed association between serum INSL3 concentrations and external genital androgenization at diagnosis or rates of spontaneous pubertal onset.…”

Clinical value of INSL3 in the diagnosis and development of diabetic nephropathy

“…A growing number of studies have studied the potential of INSL3 in clinical diagnosis or prognosis in various diseases, such as atrophy and weakness in skeletal muscle, 24 klinefelter syndrome, 25 and thyroid cancer 26 . The present study illustrated that INSL3 was abundantly expressed in DN tissues and negatively correlated with an advanced INSS stage and unfavorable prognosis.…”

“…21 In metabolic-related diseases, INSL3 was found dramatically down-regulated in obese adolescents. 22,23 and weakness in skeletal muscle, 24 klinefelter syndrome, 25 and thyroid cancer. 26 The present study illustrated that INSL3 was abun-…”

Isolation of Leydig cells from adult rat testes by magnetic‐activated cell sorting protocol based on prolactin receptor expression

“…Unlike T, these two products are not acutely regulated by LH as tightly. They are constitutively synthesised by LCs independent of steroidogenesis but nonetheless can be regarded as functional markers for LCs 33–35 . In the current study, we have also examined the synthesis of 25‐OH‐VD and expressions of the genes involved in these two products, Cyp2r1 and Insl3.…”

“…They are constitutively synthesised by LCs independent of steroidogenesis but nonetheless can be regarded as functional markers for LCs. [33][34][35] In the current study, we have also examined the synthesis of 25-OH-VD and expressions of the genes involved in these two products, Cyp2r1 and Insl3. Very interestingly, we have found mild but significantly up-regulations of all three parameters by the LH treatment for 24 h. The findings not only confirmed the previously reports that these two products were not acutely regulated by LH as tightly as for T, but also extended the previous conclusions and suggested that the long-term maintenance of these two products may still depend on LH.…”