Focal adhesion kinase (FAK) and its downstream signaling targets, mitogen‐activated protein kinase (MAPKs), are implicated in the process of phagocytosis by insect hemocytes. The goal of this study was to explore further the signaling pathways underlining the process of phagocytosis. The combination of bioinformatics, biochemical, and immunofluorescence approaches strongly support the expression of Elk‐1‐like protein in medfly hemocytes. Elk‐1 is phosphorylated in E. coli or latex beads‐challenged hemocytes and osmotic loading experiments as well as flow cytometry analysis demonstrated that Elk‐1‐like protein regulates the uptake of bacteria. RNA interference (RNAi) and pharmacological inhibitors show that the signaling for Elk‐1 phosphorylation is transmitted via FAK/Src and MAPKs pathways. Furthermore, confocal analysis clearly shows that FAK and the phosphorylated FAK at Y397 are localized in the nucleus and cytoplasm, whereas, the phosphorylated Elk‐1‐like protein is exclusively localized in the nucleus. Finally, co‐immunoprecipitation and reciprocal co‐immunoprecipitation analysis demonstrated the association of low molecular weight protein bands recognized by FAK antibodies, with Elk‐1 or phospho‐Elk‐1 at ser 383 and confocal microscopy specifies that this association occurs only in the nucleus. These results are strongly supporting that Elk‐1‐like protein is a novel protein‐binding partner for FAK, a finding that significantly broadens the potential functioning of FAK and Elk‐1 generally. Evidently, the complex participates in the process of phagocytosis in medfly hemocytes. J. Cell. Biochem. 103: 1895–1911, 2008.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the responsiveness of the hypothalamic–pituitary–thyroid (HPT) axis to changes in circulating free thyroxine (fT4). Although dose–response relationships between thyroid hormones per se and urinary iodine (UI) levels have been observed, central sensitivity to thyroid hormones in relation to UI remains unexplored. The aim of the present study was to evaluate central sensitivity to thyroid hormones (by means of the Thyroid Feedback Quantile-based Index [TFQI], which is a calculated measure, based on TSH and fT4, that estimates central sensitivity to thyroid hormones) in pregnancy and to assess whether it differs according to gestational age and/or iodine intake. Materials and Methods: One thousand, one hundred and two blood and urine samples were collected from pregnant women (with a mean age ± SD of 30.4 ± 4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH and fT4, anti-thyroid peroxidase antibodies and UI were measured in each trimester and at two months postpartum, while the TFQI was calculated for all the study samples. After the elimination of outliers, statistical analysis was conducted with analysis of variance (ANOVA) for the variables versus time period, while Pearson’s correlation was used to assess the TFQI versus UI. Results: The mean TFQI index ranged from −0.060 (second trimester) to −0.053 (two months postpartum), while the corresponding UI was 137 and 165 μg/L, respectively. The TFQI-UI correlation was marginally negative (Pearson r: −0.323, p: 0.04) and significantly positive (r: +0.368, p: 0.050) for UI values over 250 μg/L, in the first and the second trimesters of pregnancy, respectively. Discussion: The TFQI is a new index reflecting central sensitivity to thyroid hormones. A lower TFQI indicates higher sensitivity to thyroid hormones. In our sample, the TFQI was mainly positively related to iodine intake in the second trimester of pregnancy (following the critical period of organogenesis). Thus, the observed changes in the TFQI may reflect the different ways of the central action of thyroid hormones, according to the phase of pregnancy. These results have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and neurokinin B (NKB) are produced by the placenta in high amounts, and they have been implicated in several pregnancy complications associated with placental dysfunction. However, their placental expression has not been studied in PCOS. We isolated mRNA after delivery from the placentae of 31 PCOS and 37 control women with term, uncomplicated, singleton pregnancies. The expression of KISS1, NKB, and neurokinin receptors 1, 2, and 3 was analyzed with real-time polymerase chain reaction, using β-actin as the reference gene. Maternal serum and umbilical cord levels of total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), androstenedione, dehydroepiandrosterone sulfate (DHEAS), Anti-Mullerian hormone (AMH), and estradiol were also assessed. NKB placental mRNA expression was higher in PCOS women versus controls in pregnancies with female offspring. NKB expression depended on fetal gender, being higher in pregnancies with male fetuses, regardless of PCOS. NKB was positively correlated with umbilical cord FAI and AMH, and KISS1 was positively correlated with cord testosterone and FAI; there was also a strong positive correlation between NKB and KISS1 expression. Women with PCOS had higher serum AMH and FAI and lower SHBG than controls. Our findings indicate that NKB might be involved in the PCOS-related placental dysfunction and warrant further investigation. Studies assessing the placental expression of NKB should take fetal gender into consideration.