To examine the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in the control of glucocorticoid actions in the ovine pituitary during development, we have sought developmental changes in the distribution and the level of 11β-HSD1 mRNA by in situ hybridization. In the pars distalis, 11β-HSD1 mRNA was present by day 60; its amount did not change significantly until term (days 145–147) when it increased dramatically. The level of 11β-HSD1 mRNA increased further during the postnatal period. In contrast, 11β-HSD1 mRNA in the pars intermedia was not detectable until day 135; it increased in amount at days 140–143, but did not change significantly thereafter through to adulthood.
We have also measured levels of both dehydrogenase and reductase activities of 11β-HSD1 in the pars distalis of fetal sheep at day 140 and term, and of postnatal sheep at 1–2 months of age, to determine whether changes in 11β-HSD1 mRNA are reflected in the levels of enzyme activities. There were progressive increases in both dehydrogenase and reductase activities from day 140 to 1–2 months postnatally, although dehydrogenase activity was consistently higher than reductase activity.
Finally, we have determined the effect of short-term intrafetal cortisol infusion (5 μg/min for 12 h) on levels of pituitary 11β-HSD1 mRNA by in situ hybridization. There was no effect of cortisol infusion on 11β-HSD1 mRNA expression.
The present results demonstrate that 11β-HSD mRNA and enzyme activity in the pars distalis of fetal sheep increase dramatically at term when plasma levels of both ACTH and cortisol are elevated. This suggests that 11β-HSD1 may contribute to the proposed resetting of cortisol negative feedback within the fetal pituitary at that time.
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