Endocrine Abstracts

NPY acts centrally to stimulate appetite and the HPA axis. During late pregnancy enhanced inhibition of parvocellular paraventricular nucleus (pPVN) corticotrophin releasing hormone (CRH)/ arginine vasopressin (AVP) neurones reduces HPA-axis stress responses^1,2. We investigated activation of hypothalamic neurones regulating HPA responses to NPY, and a role for endogenous opioids in HPA hyporesponsiveness in late pregnancy.

Pregnant (d21) and virgin rats (n=6-8/group) were treated as follows:

NPY (5 μg, icv) ± iv naloxone (5 mg/kg) injection, with blood sampling for ACTH radioimmunoassay; brains collected at 240 min and cryostat sectioned were processed for AVP mRNA ³⁵S-oligoprobe in-situ hybridisation. Other rats were perfuse-fixed (4% paraformaldehyde) under pentobarbitone anaesthesia 90 min after icv injection of either NPY or vehicle, and coronal brain sections processed for Fos immunohistochemistry. Icv NPY significantly increased plasma ACTH concentration within 15 min in virgin (3.5-fold) but not pregnant rats, yet increased food intake in virgin and pregnant rats. NPY increased the number of Fos positive neurones in the pPVN (p<0.001) and arcuate nucleus (p<0.001) in only the virgin rats. Also, pPVN AVP mRNA expression, measured as silver grain density was significantly lower (5-fold) in the pregnant vs virgin rats after NPY. Naloxone had no further effect on ACTH in virgins but restored a response in the pregnant rats (2.5-fold), and restored an AVP mRNA response (14-fold) to NPY in pregnant rats with no effect in virgins.

Thus the responsiveness of the HPA-axis to central NPY is suppressed in late pregnancy, and endogenous opioids are involved.

¹Brunton, et al., 2003 J Neuroendocrinol. 15: 633; 2005,

²Brunton, et al., 2005, J Neurosci. 25: 5117–5126. Support: BBSRC/MRC