Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While many factors involved in pubertal initiation remain poorly understood, the kisspeptin system is known to play a key role. Currently, mutations in the kisspeptin system, MKRN3, and DLK1 have been identified in sporadic and familial cases of CPP. The diagnosis is based on physical exam findings indicating advancing puberty and on laboratory tests confirming central HPG axis activation. GnRH analogs are the mainstay of treatment and are used with the goal of height preservation. Newer extended release formulations continue to be developed. Currently there is no evidence of long-term complications associated with treatment. However, many areas remain to be explored such as targeted therapies and aspects of clinical management. Further investigation into psychological effects and additional data regarding long-term outcomes, particularly in males, is needed.

Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.

Retinoid X receptor a [RXRa; nuclear receptor (NR)2B1] is a crucial regulator in the expression of a broad array of hepatic genes under both normal and pathologic conditions. During inflammation, RXRa undergoes rapid post-translational modifications, including c-Jun N-terminal kinase (JNK)-mediated phosphorylation, which correlates with a reduction in RXRa function. A small ubiquitin-like modifier (SUMO) acceptor site was recently described in human RXRa, yet the contributors, regulators, and consequences of SUMO-RXRa are not well understood. Inflammation and other stressors alter nuclear receptor function in liver and induce SUMOylation of several NRs as part of proinflammatory gene regulation, but linkages between these two pathways in liver, or for RXRa directly, remain unexplored. We sought to determine if inflammation induces SUMOylation of RXRa in human liver-derived (HuH-7) cells. Lipopolysaccharide, interleukin-1b, and tumor necrosis factor a (TNFa) rapidly and substantially stimulated SUMOylation of RXRa. Two RXRa ligands, 9-cis retinoic acid (9cRA) and LG268, induced SUMOylation of RXRa, whereas both inflammation-and ligand-induced SUMOylation of RXRa require the K108 residue. Pretreatment with 1,9-pyrazoloanthrone (SP600125), a potent JNK inhibitor, abrogates TNFa-and 9cRA-stimulated RXRa SUMOylation. Pretreatment with SUMOylation inhibitors markedly augmented basal expression of several RXRa-regulated hepatobiliary genes. These results indicate that inflammatory signaling pathways rapidly induce SUMOylation of RXRa, adding to the repertoire of RXRa molecular species in the hepatocyte that respond to inflammation. SUMOylation, a newly described post-translational modification of RXRa, appears to contribute to the inflammation-induced reduction of RXRaregulated gene expression in the liver that affects core hepatic functions, including hepatobiliary transport.