JCI Table of Contents, Apr...( ia essentially an enlargement of the a...),Health

ia, essentially an enlargement of the adrenal glands above the kidneys. Interestingly, if the mother is given a cortisol-like drug called dexamethasone at this point in the pregnancy, the fetal genitalia can be restored back to the female form. Now, in a study appearing in the April issue of the Journal of Clinical Investigation, researcher Neil A. Hanley and colleagues at the Southampton General Hospital in the United Kingdom, report that the reason for this dexamethasone-mediated reversal is due to the drug's suppression of fetal levels of male hormones (adrenal androgens) produced by a critical determinant of gender known as the "hypothalamic-pituitary-adrenal" (HPA) axis. The researchers analyzed adrenal tissue from 121 human fetuses (following ethical approval from their research ethics committee), and found that although the adrenal gland increased in size over the course of 810 weeks of development, the content of cortisol dropped by approximately 50%. Further, the authors found that individual adrenal glands from first trimester fetuses were able to produce several different androgens, including testosterone, and that this androgen production was responsive to ACTH (a hormone of the anterior pituitary). Together these data suggest that the adrenal cortex participates in the production of cortisol and androgens during the first trimester of human development, and that adrenocortical activity is correlated to that of the anterior pituitary, and identify an important mechanism for safeguarding female sexual development.

In an accompanying commentary, Perrin C. White from the UT Southwestern Medical Center in Dallas states that "by demonstrating that there is indeed a functioning fetal HPA axis when the external genitalia are differentiating, the present work provides a rationale for prenatal treatment of congenital adrenal hyperplasia due to CYP21 deficiency." In addition, he comments that "this study implies that high doses of dexamethasone are mo
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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
3-Apr-2006

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