This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McArthur, S. Articles by Gillies, G. E. Search for Related Content PubMed PubMed Citation Articles by McArthur, S. Articles by Gillies, G. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DEXAMETHASONE DOPAMINE

Perinatal Glucocorticoid Treatment Disrupts the Hypothalamo-Lactotroph Axis in Adult Female, But Not Male, Rats

Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College (S.M., Z.-L.S., E.T., C.D.J., J.C.B., G.E.G.), London W12 0NN, United Kingdom; Respiratory Health Services Research Group, National Heart and Lung Institute, Imperial College (S.F.S.), London W6 8RF, United Kingdom; Department of Human Anatomy and Genetics, University of Oxford (H.C.C., J.F.M.), Oxford OX1 3QX, United Kingdom; and Dipartemento di Scienze Farmaceutiche, Universita di Modena e Reggio Emilia (G.C.), 41100 Modena, Italy

Address all correspondence and requests for reprints to: Dr. Glenda E. Gillies, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom. E-mail: g.gillies{at}imperial.ac.uk.

This study aimed to test the hypothesis that the tuberoinfundibular dopaminergic neurons of the arcuate nucleus and/or the lactotroph cells of the anterior pituitary gland are key targets for the programming effects of perinatal glucocorticoids (GCs). Dexamethasone was administered noninvasively to fetal or neonatal rats via the mothers’ drinking water (1 µg/ml) on embryonic d 16–19 or neonatal d 1–7, and control animals received normal drinking water. At 68 d of age, the numbers of tyrosine hydroxylase-positive (TH+) cells in the arcuate nucleus and morphometric parameters of pituitary lactotrophs were analyzed. In control animals, striking sex differences in TH+ cell numbers, lactotroph cell size, and pituitary prolactin content were observed. Both pre- and neonatal GC treatment regimens were without effect in adult male rats, but in females, the overriding effect was to abolish the sex differences by reducing arcuate TH+ cell numbers (pre- and neonatal treatments) and reducing lactotroph cell size and pituitary prolactin content (prenatal treatment only) without changing lactotroph cell numbers. Changes in circulating prolactin levels represented a net effect of hypothalamic and pituitary alterations that exhibited independent critical windows of susceptibility to perinatal GC treatments. The dopaminergic neurons of the hypothalamic periventricular nucleus and the pituitary somatotroph populations were not significantly affected by either treatment regimen in either sex. These data show that the adult female hypothalamo-lactotroph axis is profoundly affected by perinatal exposure to GCs, which disrupts the tonic inhibitory tuberoinfundibular dopaminergic pathway and changes lactotroph morphology and prolactin levels in the pituitary and circulation. These findings provide new evidence for a long-term disruption in prolactin-dependent homeostasis in females, but not males, after inappropriate GC exposure in perinatal life.

This article has been cited by other articles:

				C. C. Hoppe, R. G. Evans, J. F. Bertram, and K. M. Moritz Effects of dietary protein restriction on nephron number in the mouse Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1768 - R1774. [Abstract] [Full Text] [PDF]