DHT and Insulin Upregulate Secretion of the Soluble Decoy Receptor of IL-33 From Decidualized Endometrial Stromal Cells.

Interleukin 33 (IL-33) signaling regulates most of the key processes of pregnancy, including decidualization, trophoblast proliferation and invasion, vascular remodeling, and placental growth. Accordingly, dysregulation of IL-33, its membrane-bound receptor (ST2L, transducer of IL-33 signaling), and its soluble decoy receptor (sST2, inhibitor of IL-33 signaling) has been linked to a wide range of adverse pregnancy outcomes that are common in women with obesity and polycystic ovary syndrome, that is, conditions associated with hyperandrogenism, insulin resistance, and compensatory hyperinsulinemia. To reveal if androgens and insulin might modulate uteroplacental IL-33 signaling, we investigated the effect of dihydrotestosterone (DHT) and/or insulin on the expression of ST2L and sST2 (along with the activity of their promoter regions), IL-33 and sIL1RAP (heterodimerization partner of sST2), during in vitro decidualization of endometrial stromal cells from 9 healthy women. DHT and insulin markedly upregulated sST2 secretion, in addition to the upregulation of its messenger RNA (mRNA) expression, while the proximal ST2 promoter, from which the sST2 transcript originates, was upregulated by insulin, and in a synergistic manner by DHT and insulin combination treatment. On the other hand, sIL1RAP was slightly downregulated by insulin and IL-33 mRNA expression was not affected by any of the hormones, while ST2L mRNA expression and transcription from its promoter region (distal ST2 promoter) could not be detected or showed a negligibly low level. We hypothesize that high levels of androgens and insulin might lead to subfertility and pregnancy complications, at least partially, through the sST2-dependent downregulation of uteroplacental IL-33 signaling.

IGF-I and IGFBP-1 in Relation to Body Composition and Physical Performance in Female Olympic Athletes.

Introduction: Insulin- like growth factor-I (IGF-I) is an anabolic hormone that may affect athletic performance in female athletes, and insulin-like growth factor binding protein-1 (IGFBP-1) is an important regulator of bioactive IGF-I. There is limited knowledge of the role of endogenous IGF-I and IGFBP-1 for body composition and physical performance in female elite athletes. Purpose: To examine IGF-I, age adjusted IGF-I (IGFSD), IGFBP-1 and insulin in female Olympic athletes compared with controls and different sport categories, and in relation to body composition and physical performance in the athletes. Methods: Female athletes (n=103) and untrained controls (n=113) were included in this cross-sectional study. Body composition was established by dual-energy X-ray absorptiometry. Serum IGF-I and IGFBP-1 were analyzed by radioimmunoassay and IGFSD was calculated. Insulin was analyzed by electrochemiluminescence immunoassay. Athletes were offered to participate in standardized physical fitness tests. Results: The athletes demonstrated significantly higher IGF-I, IGFSD and IGFBP-1 and lower insulin levels than controls (p<0.05, p<0.05, p<0.01, p<0.001 respectively). Power athletes had significantly higher IGFSD compared to both endurance and technical athletes (p<0.05, p<0.01, respectively). In athletes and controls combined, significant positive correlations were found between IGF variables and higher bone mineral density (BMD) and lean mass and lower fat percent. IGF-I was positively correlated with squat jump (rs = 0.28, p<0.05) and IGFBP-1 correlated positively with squats (rs =0.35, p<0.05). Conclusion: We found higher IGF-I, IGFSD and IGFBP-1 in female athletes than controls, and the highest IGFSD in power athletes. IGF-I and IGFBP-1 were related to increased BMD and lean mass and lower fat percent, as well as were positively associated with physical fitness tests. Future studies are needed to elucidate if these results reflect adaptive responses to physical activity or genetic predisposition.