Adropin Stimulates Proliferation and Inhibits Adrenocortical Steroidogenesis in the Human Adrenal Carcinoma (HAC15) Cell Line.

Adropin is a multifunctional peptide hormone encoded by the ENHO (energy homeostasis associated) gene. It plays a role in mechanisms related to increased adiposity, insulin resistance, as well as glucose, and lipid metabolism. The low adropin levels are strongly associated with obesity independent insulin resistance. On the other hand, overexpression or exogenous administration of adropin improves glucose homeostasis. The multidirectional, adropin-related effects associated with the regulation of metabolism in humans also appear to be attributable to the effects of this peptide on the activity of various elements of the endocrine system including adrenal cortex. Therefore, the main purpose of the present study was to investigate the effect of adropin on proliferation and secretory activity in the human HAC15 adrenal carcinoma cell line. In this study, we obtained several highly interesting findings. First, GPR19, the main candidate sensitizer of adrenocortical cells to adropin, was expressed in HAC15 cells. Moreover, GPR19 expression was relatively stable and not regulated by ACTH, forskolin, or adropin itself. Our findings also suggest that adropin has the capacity to decrease expression levels of steroidogenic genes such as steroidogenic acute regulatory protein (StAR) and CYP11A1, which then led to a statistically significant inhibition in cortisol and aldosterone biosynthesis and secretion. Based on whole transcriptome study and research involving transforming growth factor (TGF)-ß type I receptor kinase inhibitor we demonstrated that attenuation of steroidogenesis caused by adropin is mediated by the TGF-ß signaling pathway likely to act through transactivation mechanism. We found that HAC15 cells treated with adropin presented significantly higher proliferation levels than untreated cells. Using specific intracellular inhibitors, we showed that adropin stimulate proliferation via ERK1/2 and AKT dependent signaling pathways. We have also demonstrated that expression of GPR19 is elevated in adrenocortical carcinoma in relation to normal adrenal glands. High level of GPR19 expression in adrenocortical carcinoma may constitute a negative prognostic factor of disease progression.

Cervical screening in Western Kazakhstan: Liquid-based cytology 'Cell Scan' versus azur-eosin staining.

OBJECTIVE: To assess the effectiveness of the current cervical cancer screening tools in Western Kazakhstan. METHODS: Smears taken through (i) conventional cytology using azur-eosin staining and (ii) liquid-based cytology (LBC) 'Cell Scan' in the general female population and in women first diagnosed with cervical cancer were collected throughout the region. ROC-analysis with curve construction and weighted Cohen's κ calculation were applied. A total of 494 cytological pairs were collected, including 94 sets with histology findings. RESULTS: The conventional (azur-eosin staining) technique contained 0.2% non-informative material and LBC 'Cell Scan' had 5.9%. Area under the curve was 0.95 for the conventional technique and 0.92 for 'Cell Scan' (p > 0.05). The conventional smears showed κ 0.62, sensitivity 90.4% at specificity 90.0% for CIN2+, while LBC 'Cell Scan' smears showed κ 0.47, sensitivity 83.3% at specificity 92.5%. CONCLUSIONS: In this analysis it was not possible to prove that the LBC 'Cell Scan' technique was superior to its predecessor, azur-eosin staining. These findings highlight the need to modify the current screening programme according to updated international scientific evidence on effective screening design, such as the use of HPV DNA testing with Pap smear triage in women aged 30 or older. Further research, and a Health Technology Assessment, are necessary if we wish to establish a national standardized screening programme using the available technology appropriately.