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Glucocorticoids Do Not Alter Developmental Expression of Hippocampal or Pituitary Steroid Receptor Coactivator-1 and -2 in the Late Gestation Fetal Guinea Pig

Departments of Physiology (E.S., D.O., L.M., A.K., M.H.A., S.G.M.), Obstetrics and Gynecology (S.G.M.), and Medicine (S.G.M.), Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Address all correspondence and requests for reprints to: Dr. S. G. Matthews, Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8. E-mail: stephen.matthews{at}utoronto.ca.

Steroid receptor coactivator (SRC) proteins interact with glucocorticoid receptors in a ligand-dependent manner to enhance transcription. Although glucocorticoids are essential for normal brain maturation, little is known about the presence or regulation of SRC proteins in the developing central nervous system. In the current study we demonstrated that SRC-1 was highly expressed in the fetal limbic system (hippocampal CA3>CA1/2>CA4>dentate gyrus) at gestational d (gd) 40 (term, 70 d), whereas SRC-2 was undetectable at all time points. Hippocampal SRC-1 mRNA and protein expression were reduced in male and female fetuses with advancing gestation. In contrast, SRC-1 mRNA levels increased significantly in the dentate gyrus near term. Repeated maternal injection (1 or 10 mg/kg on gd 40, 41, 50, 51, 60, and 61) with synthetic glucocorticoid had no effect on fetal limbic SRC-1 expression at gd 62 in either sex. SRC-1 and SRC-2 mRNA expression in the anterior pituitary did not change over the second half of gestation and was unaffected by prenatal exposure to synthetic glucocorticoid. In conclusion, SRC-1 expression undergoes spatial, temporal, and region-specific regulation during development, and limbic and pituitary SRC-1 and SRC-2 are not regulated by glucocorticoids in late gestation. Developmental changes in limbic SRC-1 expression probably have important consequences on steroid receptor signaling, which is known to be critical for brain maturation in late gestation.

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