Alteration of pituitary-adrenal responses to adrenalectomy by the immunological targeting of CRF neurons.
We previously demonstrated that cellular toxins added to a cytotoxic IgG2a monoclonal antibody to corticotropin releasing factor (CRF-MAb) may specifically penetrate some hypothalamic CRF neurons, after central injection near the paraventricular nuclei. We attempt here to evaluate the consequential effects on the CRF neurons functioning. Such a toxic mix, 4 weeks after its central injection, caused a marked reduction (66%) of the chronic adrenocorticotropic hormone (ACTH) release in response to a bilateral adrenalectomy (7th day). This change was accompanied by a reduction in the CRF concentration (43%) measured in the median eminence. We concluded that specific internalization of toxins, by the way of CRF-MAb, leads to a long-term dysregulation of the CRF synthesis and/or neuronal transport.
Menzaghi
F
F
Laboratory of Cellular Biology, INSERM U.308, Nancy, France.
Burlet
A
A
Chapleur
M
M
Nicolas
J P
JP
Burlet
C
C
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012016:Reference Values
D011498:Protein Precursors; D012333:RNA, Messenger; C041645:pro-corticotropin releasing hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone