Dexamethasone counteracts the effect of prolactin on islet function: implications for islet regulation in late pregnancy.

摘要: Islets undergo a number of up-regulatory changes to meet the increased demand for insulin during pregnancy, including secretion and beta-cell proliferation. It has been shown that elevated lactogenic hormone is directly responsible these changes, which occur in phasic pattern, peaking on day 15 pregnancy returning control levels by 20 (term). As placental lactogen remain through late gestation, it was interest determine whether glucocorticoids (which increase gestation) could counteract effects lactogens secretion, proliferation, apoptosis. We found measured over 24 h culture acute 1 response high glucose were at least 2-fold PRL treatment after 6 days culture. Dexamethasone (DEX) had significant inhibitory effect dose-dependent manner concentrations greater than nM. At 100 nM, concentration equivalent plasma corticosteroid level DEX inhibited below levels. The addition (>1 nM) from PRL-treated islets similar those produced alone. Bromodeoxyuridine (10 microM) staining final 6-day showed cell proliferation 6-fold level. alone (1-1000 did not reduce division level, but significantly rate islets. YoYo-1, an ultrasensitive fluorescent nucleic acid stain, added (1 microM; 8 h) medium 1-3 examine death. examined under confocal microscopy (100 cells with apoptotic nuclear morphologies. This quantified counting YoYo-labeled nuclei per islet conventional epifluorescence microscopy. numbers YoYo-1-positive different 3 However, YoYo-1 labeling 7-fold controls. also 3-fold These data show glucocorticoid stages effectively reverse PRL-induced up-regulation function inhibiting while increasing