Ontogeny of androgen receptor expression in the ovine fetal central nervous system and pituitary

Abstract

In fetal sheep, circulating androgens influence fetal stress responsiveness and timing of parturition. Nevertheless, little is known about the presence and development of androgen receptors in the fetal brain. The present study was undertaken to test the hypothesis that expression of androgen receptor occurs in fetal brain and pituitary, and that the abundance of the AR is ontogenetically regulated. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brainstem in fetal sheep that were 80, 100, 120, 130, 145 days gestation, and 1 and 7 days postnatal (n=4-5/group). Using real-time RT-PCR, we measured mRNA expression levels of the receptor in these brain regions and pituitary. In a separate study, we isolated protein from the same brain regions in fetal sheep that were 80 (n=3), 120 (n=4), and 145 (n=4) days. AR mRNA expression in hypothalamus increased in late gestation, starting at 145 days, and increasing progressively after birth. A trend of increasing AR protein in hypothalamus was not significant. AR mRNA expression in pituitary was elevated after 80 days gestation, but with no further increases or decreases in late gestation, while AR protein increased significantly at the end of gestation. In hippocampus and brainstem AR mRNA was constant throughout the latter half of gestation, and AR protein was below the sensitivity of our western blot assay. We conclude that the fetal brain and pituitary are target sites for circulating androgens or androgen precursors in fetal plasma, and we speculate that the increase in hypothalamic action of androgens immediately prior to birth might be integral to the timing of parturition. Keywordsreal-time PCR; sheep; parturition; neuroendocrinology; placenta; adrenal In fetal sheep, there are several notable developmental changes in the neuroendocrine control mechanisms that prepare the fetus for postnatal life. We and others have reported maturational changes in the neuroendocrine components of the fetal hypothalamus-pituitary-adrenal axis; the development of this endocrine axis is important for the development of appropriate fetal responses to stress as well as the control of parturition in this species [1]. Late gestation is characterized by marked changes in the concentrations of several steroid hormones, including glucocorticoids, estrogens, and androgens [2][3][4][5][6]. We have recently reported developmental changes in the expression of glucocorticoid and mineralocorticoid receptors in fetal brainstem, hypothalamus, and pituitary [7]. For example, decreases in the pituitary expression of the Address all correspondence to: Charles E. Wood, Ph.D., Box 100274, Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610-0274. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting pro...

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