The foetus, though protected by the placental barrier, is highly susceptible to changes in both maternal diet and the hormonal milieu. In particular, a chronically poor maternal diet resulting from either protein/calorie restriction or excess maternal nutrients, as well as elevated hormones, such as insulin and glucocorticoids, have major consequences for foetal development and metabolic disease in adult life. Maternal under-nutrition, for example, can lead to intrauterine growth retardation, which is linked to an increased risk of diabetes, hypertension and cardiovascular disease in the adult offspring [1–3]. Emerging evidence also suggests that maternal over-nutrition may have similar long-term metabolic consequences in the offspring [4–6], but the mechanisms underlying the foetal origins of these diseases have only begun to be investigated. The concept of foetal ‘programming’describes a change in gene expression due to an environmental exposure in utero, resulting in a persistent altered metabolic phenotype in the adult offspring [7]. During development, glucocorticoids are essential for organ maturation, particularly the foetal lung. Administration of synthetic glucocorticoids is currently recommended for mothers at risk of preterm and delivery between 24–36 weeks, in order to promote proper foetal lung maturation, and is successful in reducing neonatal mortality and chronic lung disease [8]. Numerous laboratories have, however, provided compelling evidence that foetal exposure to inappropriate amounts of glucocorticoids has profound effects on foetal growth, placental function, and foetal and post-natal brain development, and can result in persistent hyperglycaemia throughout life [9–11]. Suboptimal maternal nutrition [12] and maternal stress [13, 14] are also thought to expose the foetus to excess glucocorticoids. Regardless of the source, elevated glucocorticoid levels during pregnancy predispose to in utero growth retardation and low birthweight [15, 16]. In this issue of Diabetologia, Nyirenda et al.[17] report an exciting new potential mechanism for glucocorticoidinduced foetal programming of hyperglycaemia. The authors’ previous work demonstrated that exposure to prenatal dexamethasone resulted in persistent upregulation of the mRNA and activity of the cytosolic form of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK) in adult offspring [18]. Furthermore, these changes in PCK expression in adult offspring could not be attributed to altered postnatal maternal behaviour, suggesting that excess foetal glucocorticoid exposure has a permanent effect, programming increased gluconeogenesis [19]. Nyirenda et al.[17] have now followed up this work by investigating the effects of supraphysiological levels of glucocorticoids, administered to female rats during the last week of pregnancy, on key hepatic transcription factors known to regulate PCK expression in the rat foetus and adult offspring. Prenatal dexamethasone resulted in an early increase in the transcription of the gene encoding foetal hepatic nuclear factor 4 (Hnf4a), which remained elevated into adulthood, and paralleled the rise in Pck1 expression and hyperglycaemia. Interestingly, dexamethasone treatment not only increased Hnf4a mRNA expression, but altered the expression of the of Hnf4a isoforms, such that the adult isoforms (Hnfa1/2) were favoured over the foetal isoforms (Hnf4a7/8). Expression of the different isoforms results from alternative promoter usage and differential splicing. An early promoter switch to produce