Endocrine Abstracts (2001) 2 OC10

Hypothalamo-Pituitary-Adrenal (HPA) Responses to Centrally Administered Orexin-A Are Attenuated in Pregnant Rats

PJ Brunton, C Wilkinson & JA Russell


Department of Biomedical and Clinical Laboratory Sciences; University of Edinburgh; Edinburgh; Scotland.


Orexins are hypothalamic peptides known to stimulate food intake. Recently, orexins have been shown to activate the HPA axis at a central level1. We have previously shown that during late pregnancy the responsiveness of the HPA axis to a range of stressors is attenuated and suggested that the corticotropin releasing hormone (CRH) neurones or pathways impinging on them are less responsive2. If the CRH neurones themselves are less responsive, they should also respond less to other stimuli. Thus, we investigated HPA axis responses to centrally administered orexin-A during pregnancy. Five days prior to the experiment, female virgin and pregnant (d16) Sprague Dawley rats were fitted with an intracerebroventricular (icv) and a jugular vein (iv) cannula under halothane anaesthesia. On the day of the experiment, cannulae were connected and blood samples were withdrawn before and after administration of 2microlitres icv orexin-A (0.25micrograms/microlitre) or vehicle (aCSF). Plasma ACTH and corticosterone concentrations were determined by radioimmunoassay. Brain sections were processed by in situ hybridisation with a radiolabelled oligo-probe complementary to CRH mRNA. Virgin rats treated with orexin-A (n=5) demonstrated a significant rise in plasma ACTH within 10min, which remained elevated over 90min. However icv orexin-A failed to evoke any such effect on ACTH levels in the pregnant (d21) group (n=8). Similarly, orexin-A increased corticosterone secretion significantly only in the virgin group. Quantification of autoradiographs revealed that CRH mRNA expression in the paraventricular nucleus (PVN) of vehicle treated groups was significantly lower in pregnant (n=8) compared with virgin rats (n=5). Orexin-A significantly increased CRH mRNA expression in the virgin group (n=8) and this response was absent in the pregnant group (n=9). Thus, in pregnancy the responsiveness of PVN CRH neurones, and hence the HPA axis to the appetite stimulating peptide: orexin-A, is markedly reduced. [Support: PJB receives a Faculty of Medicine Research Scholarship]. References: 1Jaszberenyi, M et al (2000) J Neuroendocrinol; 12: 1174. 2Brunton, PJ et al (2000) Eur J of Neurosci12; 184.17.

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