Inhibition of corticotropin releasing factor (CRF)-induced adrenocorticotropin (ACTH) secretion in pituitary corticotropic cells by substance P.

Substance P (SP) is one of the three distinct peptides of tachykinin system which possess a common spectrum of biological activities including a modulation of stress. It is assumed that the anterior pituitary is one possible target of SP in attenuation the stress response. Therefore the interaction between the hypothalamic stress hormone corticotropin releasing factor (CRF) and SP was investigated in AtT20/D16v-cells, a cellular model derived from a pituitary tumor. CRF stimulates the release of ACTH from AtT20/D16v cells in a concentration dependent manner. SP (1 microM) was able to abolish the CRF (100 nM)-induced ACTH release. In the same way SP inhibited the CRF-induced accumulation of cyclic adenosine monophosphate (cAMP), indicating that SP influenced the signal transduction pathway of CRF receptor activation. Thus, a direct inhibition of the CRF-mediated stress response by SP at the level of anterior pituitary seems to be likely.