CHANGES IN GLUCOCORTICOID RECEPTOR MESSENGER-RNA IN THE DEVELOPING OVINE PITUITARY AND THE EFFECTS OF EXOGENOUS CORTISOL

Developmental changes in pituitary glucocorticoid receptor (GR) mRNA w ere examined during gestation and early neonatal life using in situ hy bridization. Pituitaries were harvested from sheep fetuses at days 60- 80, 100-120, 130-135, 140-142 and term, and from lambs of days 0-7 and 30-60, and adults. GR mRNA was present in the pars distalis by day 60 , levels increased through gestation, and there was a redistribution o f GR mRNA, resulting in a relatively greater abundance at the base of the pars distalis. At term, there was a significant (P<0.05 compared w ith the day 140-142 fetuses) elevation of GR mRNA, which was maintaine d in the newborn lamb, reaching highest levels at days 30-60 of neonat al life. GR mRNA was undetectable in the pars intermedia until day 120 , but subsequently increased to high levels at term. Interestingly, th e expression of GR mRNA in the pars intermedia dropped precipitously i n the newborn (P<0.05 compared with term), though levels recovered in the older lambs and adults. The regional and cellular distribution of GR mRNA correlated closely with the presence of immunoreactive GR (irG R) in the pituitary; the majority of irGR was present in the nuclei. I ntrafetal infusion of cortisol (12 h; 5 mu g/min) in late gestation (d ay 135) had no effect on GR mRNA expression in either the pars distali s or pars intermedia. These results indicated that, in the fetal pitui tary, (1) the GR gene is expressed in both the pars distalis and pars intermedia, (2) levels of GR mRNA in the fetal pituitary correlated wi th the distribution of nuclear irGR, (3) GR mRNA is present at higher levels in the. inferior aspect of the pars distalis, its abundance inc reases immediately prior to parturition and is maintained in the newbo rn, and (4) cortisol infusion for 12 h does not affect GR mRNA in eith er region of the pituitary, suggesting that, in the shea term, glucoco rticoids do not directly regulate GR synthesis.