Androgen receptor (AR)-interacting protein 3 (ARIP3/ PIASx␣) is a coregulator capable of modulating transcriptional activity of various steroid receptors. We have characterized functional regions of ARIP3 and studied its interaction with the glucocorticoid receptor (GR)-interacting protein 1 (GRIP1). We find that the potential zinc-binding domain is critical for ARIP3 to function as a coactivator; the deletion of amino acids 347-418 or the mutation of the conserved cysteines 385 and 388 to serines converts ARIP3 to a transcriptional repressor from AR-dependent minimal promoters and abolishes its ability to activate GR. By contrast, mutations in the two LXXLL motifs of ARIP3 have relatively minor effects on its ability to regulate AR or GR function. ARIP3 is able to interact with different regions of GRIP1, but the strongest interaction is detected with the C-terminal region (amino acids 1122-1462) of GRIP1. The interaction of ARIP3 with the latter GRIP1 domain or full-length GRIP1 and the ability of ARIP3 to cooperate with GRIP1 in the regulation of AR-or GR-dependent transcription are dependent on the ARIP3 zinc-binding region. We also find a strong synergism between GRIP1 and two other PIAS family members, Miz1 and PIAS1. Taken together, our results suggest that PIAS proteins and GRIP1 interact functionally in transcriptional regulation.

Objective: We investigated circulating markers of bone turnover before and during systemic glucocorticoid treatment in paediatric patients with inflammatory bowel disease (IBD). Methods: Twenty-two children (mean age, 12.3 years) with IBD necessitating peroral steroid therapy were studied, with special reference to bone formation and resorption markers amino-terminal type I collagen propeptide (PINP) and carboxyterminal telopeptide of type I collagen (ICTP) respectively. In addition, GH-related IGF-I and sex hormone-binding protein (SHBG) were measured. Bone markers were analyzed at the initiation of the glucocorticoid treatment, at 2 and 5 weeks thereafter and at 1 month following the withdrawal of the steroid. Control group comprised 22 IBD patients in remission.Results: PINP and IGF-I were already lower before glucocorticoid treatment serum in children with active IBD as compared with control children with IBD in remission (median PINP 271 vs 535 mg/l, P!0.05; IGF-I 23 vs 29 nmol/l, P!0.05). After 2 weeks of glucocorticoid treatment serum PINP levels had declined further, from 271 to 163 mg/l (P!0.001), serum ICTP from 14.2 to 9.6 mg/l (P!0.001), and SHBG from 54 to 35 nmol/l (P!0.001) respectively. By contrast, serum IGF-I increased from 23 to 37 nmol/l (P!0.001). One month after the withdrawal of the glucocorticoid, all bone markers restored to levels similar to the controls. Conclusions: Bone formation in children with active IBD appears compromised and systemic glucocorticoid treatment further suppresses bone turnover. After the cessation of the glucocorticoid the bone markers show immediate improvement.European Journal of Endocrinology 159 693-698

Prednisolone doses used in the treatment of pediatric inflammatory bowel disease patients elicit a 4-fold increase in serum GBA that is significantly higher than the increase induced by budesonide. The GBA measurement is an additional tool for assessing steroid therapy at an individual level during systemic glucocorticoid treatment.