Previous studies have shown that the responsiveness of porcine preadipocytes to glucocorticoids increases progressively with fetal age. In the current study, the development of fetal glucocorticoid receptors in porcine preadipocytes was examined in primary cultures derived from 50-, 75-, and 105-d fetal and 7-d postnatal porcine adipose tissue. Three dams were used for each fetal age group and three young pigs were used for the postnatal studies. Using [3H]dexamethasone as the radioligand, cytosolic glucocorticoid receptors were measured in preadipocytes. There was an age-related increase in the number of glucocorticoid receptors during fetal development. The number of glucocorticoid receptors was very low in 50-d fetal porcine preadipocytes (1.350 +/- .178 fmol/mg of protein) and increased progressively to a peak at 105 d (8.990 +/- .741 fmol/mg of protein). This represents an approximate sixfold increase in receptor number between these two ages (P < .05). After birth, the glucocorticoid receptor number significantly decreased compared with that of 105-d fetuses (2.766 +/- .218 fmol/mg of protein, P < .05). Furthermore, the dissociation constant (Kd) of the glucocorticoid receptor in 105-d fetal preadipocytes was numerically smaller than the Kd of receptors derived from other age groups, although only significantly lower than that of the 75-d group (P < .05). Insulin markedly increased the number and binding affinity of glucocorticoid receptors in preadipocytes, indicating its potential involvement in regulation of glucocorticoid receptors. The effect of glucocorticoids on differentiation in preadipocytes is, at least in part, mediated by the number of glucocorticoid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)