PurposeThis descriptive study was aimed to examine trends in the incidence of melanoma and nonmelanoma in South Korea.Materials and MethodsThe nationwide incidence data for melanoma and non-melanoma skin cancer was obtained from the Korea Central Cancer Registry. Age-standardized rates were calculated and analyzed, using a Joinpoint regression model.ResultsThe incidence of basal cell carcinoma has increased dramatically both in men (average annual percentage change [AAPC], 8.0 [95% confidence interval (CI), 6.0 to 10.1]) and women (AAPC, 9.0 [95% CI, 7.5 to 10.4]). Squamous cell carcinoma has also steadily increased both in men (AAPC, 3.3 [95% CI, 2.6 to 4.0]) and women (AAPC, 6.8 [95% CI, 5.3 to 8.4]). Cutaneous melanoma increased continuously from 1999 to 2014 inwomen (AAPC, 3.5 [95% CI, 2.4 to 4.6]), whilst rapidly increasing in men until 2005 (APC, 7.9 [95% CI, 2.4 to 13.7]) after which no increase has been observed (APC, ‒0.2 [95% CI, ‒2.3 to 2.0]).ConclusionThe incidence rates of melanoma and non-melanoma skin cancer have increased over the past years, with the exception of melanoma in men. Further studies are required to investigate the reasons for the increased incidence of these skin cancers in South Korea.

The normal pattern of daily glucocorticoid production in mammals requires circadian modulation of hypothalamicpituitary-adrenal axis activity. To assess both the factors responsible for imparting this diurnal profile and its physiologic importance, we have exploited corticotropin-releasing hormone (

The response of pituitary gonadotropes to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GnRHR) on the cell surface, which is mediated in part at the level of gene expression. Several factors are known to affect expression of the mouse GnRHR (mGnRHR) gene, including GnRH and activin. We have previously shown that activin augments GnRH-mediated transcriptional activation of mGnRHR gene, and that region ؊387/؊308 appears to be necessary to mediate this effect. This region contains two overlapping cis-regulatory elements of interest: GnRHR activating sequence (GRAS) and a putative SMAD-binding element (SBE). This study investigates the role of these elements and their cognate transcription factors in transactivation of the mGnRHR gene. Transfection studies confirm the presence of GnRH-and activin-response elements within ؊387/؊308 of mGnRHR gene promoter. Competition electrophoretic mobility shift assay experiments using ؊335/ ؊312 as probe and ␣T3-1 nuclear extract or SMAD, Jun, and Fos proteins demonstrate direct binding of AP-1 (Fos/Jun) protein complexes to ؊327/؊322 and SMAD proteins to ؊329/؊328. Further transfection studies using mutant constructs of these cis-regulatory elements confirm that both are functionally important. These data define a novel cis-regulatory element comprised of an overlapping SBE and newly characterized non-consensus AP-1 binding sequence that integrates the stimulatory transcriptional effects of both GnRH and activin on the mGnRHR gene.

Abstract-Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are important pathogenic mechanisms in atherosclerosis and restenosis after vascular injury. In this study, we investigated the effects of

It is very likely that IGH is a phenomenon associated with the skin's normal aging process and repeated microtrauma to skin.

The response of the pituitary gonadotrope to gonadotropin-releasing hormone (GnRH) correlates directly with the concentration of GnRH receptors (GnRHR) on the cell surface, which is mediated in part at the level of GnRHR gene expression. Several hormones have been implicated in this regulation, most notably GnRH itself. Despite these observations and the central role that GnRH is known to play in reproductive development and function, the molecular mechanism(s) by which GnRH regulates transcription of the GnRHR gene has not been well elucidated. Previous studies in this laboratory have identified and partially characterized the promoter region of the mouse GnRHR gene and demonstrated that the regulatory elements for tissue-specific expression as well as for GnRH regulation are present within the 1.2-kilobase 5-flanking sequence. By using deletion and mutational analysis as well as functional transfection studies in the murine gonadotrope-derived ␣T3-1 cell line, we have localized GnRH responsiveness of the mouse GnRHR gene to two DNA sequences at ؊276/؊269 (designated Sequence Underlying Responsiveness to GnRH-2 (SURG-2), which contains the consensus sequence for the activating protein-1-binding site) and ؊292/؊285 (a novel element designated SURG-1), and demonstrated that this response is mediated via protein kinase C. By using the electrophoretic mobility shift assay, we further demonstrate that a member(s) of the Fos/Jun heterodimer superfamily is responsible in part for the DNA-protein complexes formed on SURG-2, using ␣T3-1 nuclear extracts. These data define a bipartite GnRH response element in the mouse GnRHR 5-flanking sequence and suggest that the activating protein-1 complex plays a central role in conferring GnRH responsiveness to the murine GnRHR gene.

The factors controlling the migration of mammalian gonadotropin-releasing hormone (GnRH) neurons from the nasal placode to the hypothalamus are not well understood. We studied whether the extracellular calcium-sensing receptor (CaR) promotes migration/chemotaxis of GnRH neurons. We demonstrated expression of CaR in GnRH neurons in the murine basal forebrain and in two GnRH neuronal cell lines: GT1-7 (hypothalamus derived) and GN11 (olfactory bulb derived). Elevated extracellular Ca2+concentrations promoted chemotaxis of both cell types, with a greater effect in GN11 cells. This effect was CaR mediated, as, in both cell types, overexpression of a dominant-negative CaR attenuated high Ca2+-stimulated chemotaxis. We also demonstrated expression of a β-chemokine, monocyte chemoattractant protein-1 (MCP-1), and its receptor, CC motif receptor-2 (CCR2), in the hypothalamic GnRH neurons as well as in GT1-7 and GN11 cells. Exogenous MCP-1 stimulated chemotaxis of both cell lines in a dose-dependent fashion; the effect was greater in GN11 than in GT1-7 cells, consistent with the higher CCR2 mRNA levels in GN11 cells. Activating the CaR stimulated MCP-1 secretion in GT1-7 but not in GN11 cells. MCP-1 secreted in response to CaR stimulation is biologically active, as conditioned medium from GT1-7 cells treated with high Ca2+promoted chemotaxis of GN11 cells, and this effect was partially attenuated by a neutralizing antibody to MCP-1. Finally, in the preoptic area of anterior hypothalamus, the number of GnRH neurons was ∼27% lower in CaR-null mice than in mice expressing the CaR gene. We conclude that the CaR may be a novel regulator of GnRH neuronal migration likely involving, in part, MCP-1.

Molecular mechanisms underlying gonadotrope-specific and hormonal regulation of FSHbeta gene expression remain largely unknown. We have studied the role of pituitary homeobox 1 (Ptx1), a transcription factor important for regulation of many pituitary-specific genes, in the regulation of rat FSHbeta (rFSHbeta) gene transcription. We demonstrate that Ptx1 activates the rFSHbeta gene promoter both basally and in synergy with GnRH. The effect of Ptx1 was localized to -140/-50, a region also important for basal activity of the promoter. Two putative Ptx1 binding sites (P1 and P2) homologous to consensus Ptx1 binding elements were identified in this region. We demonstrate specific binding of Ptx1 to the P2 but not to the P1 site. Furthermore, functional studies indicate that the P2 but not the P1 site mediates activation of the promoter by Ptx1. Residual activation of the promoter by Ptx1 was observed independent of the P2 site. However, no additional Ptx1 binding sites were identified in this region, indicating that the residual activation observed is likely independent of direct Ptx1 binding to the promoter. These results identify a functional Ptx1 binding site in the rFSHbeta gene promoter and suggest the presence of an additional activating pathway that is independent of direct binding of Ptx1 to the promoter.