Adrenalectomy dramatically modifies the dynamics of neuropeptide and c-fosgene responses to stress in the hypothalamic paraventricular nucleus

We have used in situ hybridization and radio-immunoassay to compare tempora l dynamics of components in the hypothalamo-pituitary limb of the hypothala mo-pituitary-adrenal axis during sustained hypovolemic stress in adrenalect omized (ADX) rats to those previously reported in intact animals. We asked three questions: first, does corticotropin-releasing hormone (CRH) gene tra nscription occur in neuroendocrine neurones of the hypothalamic paraventric ular nucleus (PVH) of ADX rats, and if so, how is it temporally organized; second, what is the expression pattern of the vasopressin and other genes k nown to be colocalized in these neuroendocrine neurones; third, if adrenoco rticotropin hormone (ACTH) secretion occurs, what is its temporal profile? We found that sustained hypovolemia evoked a brief episode of CRH gene tran scription in ADX rats that occurred earlier than in intact rats. However, i n contrast to saline-injected controls, this activation was not maintained because declines in CRH hnRNA and mRNA were seen as the stress continued. A lthough increased vasopressin gene transcription was not seen in intact hyp ovolemic rats, robust increases were measured throughout in ADX rats, sugge sting that in the absence of corticosterone the vasopressin gene is transcr ibed preferentially to the CRH gene during sustained hypovolemia. c-fos and preproenkephalin mRNA profiles also exhibited earlier onsets compared to i ntact rats. Finally, the onset and duration of ACTH secretion was the same in ADX rats as previously reported in intact rats. Collectively, these data support two hypotheses regarding the actions of corticosterone. First, tha t it provides some form of facilitatory signal allowing neuroendocrine CRH transcriptional mechanisms to remain active during sustained hypovolemia. S econd, that it strongly inhibits the response of the vasopressin gene to hy povolemic stress.