Endocrine Abstracts

Our recent studies show that perinatal exposure to the synthetic glucocorticoid (GC), dexamethasone, altered the number of dopaminergic cell bodies in mesencephalic nuclei in adult male and female rats, with implications for mood, behaviour and motor activity. The present study therefore aimed to determine whether hypothalamic dopaminergic populations are also subject to such 'programming' effects. Using timed pregnant rats, dexamethasone was included in the drinking water between gestational days 16-19 or postnatal days 1-7. At 70 days of age the tyrosine hydroxylase immunoreactive (THir) cell numbers in the arcuate nucleus were significantly greater in control females compared with males. Both pre- and neonatal exposure to dexamethasone abolished these sex differences by reducing cell numbers in the female, while having no effect in males. No sex differences or GC responsiveness were seen in the THir cells of the periventricular nucleus. As arcuate dopaminergic neurones play a significant role in regulating prolactin secretion, levels of prolactin in the pituitary gland and circulation were also measured, using radioimmunoassay. Neither parameter was affected by early dexamethasone exposure in male rats. In contrast, the female-dominant sex difference in pituitary prolactin content in control animals was significantly attenuated by prenatal, but not postnatal, dexamethasone administration, whereas circulating levels were significantly increased by postnatal, but not pre-natal treatment. These results are the first to reveal a differential responsiveness of hypothalamic dopaminergic populations to the organisational actions of glucocorticoids which differs, yet again, from responses seen in the mid-brain dopaminergic populations of the ventral tegmental area and substantia nigra. They also demonstrate a time-dependent and gender specific susceptibility of the hypothalamo-pituitary-prolactin axis to GC programming. The particular susceptibility of the female may have possible implications for the development of pathophysiological changes in the whole animal.

Acknowledgements: This work was supported by the Wellcome Trust, the Medical Research Council UK and Hammersmith Hospitals Research Trust.