Effect of AVP on susceptibility of ovine pituitary cells to a cytotoxic analogue of CRF.

Although exposure to arginine vasopressin (AVP) has been reported to induce anterior pituitary corticotrophs to bind and become responsive to corticotropin-releasing factor (CRF), the identity of these inducible CRF target cells is unknown. Such cells may themselves be the AVP-responsive corticotrophs or other cells that become CRF targets secondary to a paracrine signal from AVP target cells. The present study used a cytotoxin (Cx), specific for CRF target cells, that eliminates responses of treated cells to a subsequent challenge with CRF but leaves responses to AVP intact. We hypothesized that, if AVP target corticotrophs themselves become CRF targets, then the addition of AVP during treatment with Cx should render these cells susceptible to the cytotoxin and should eliminate the response to subsequent AVP as well. Ovine pituitary cells were chosen for the study because they respond more robustly than rat cells to AVP. Pretreatment of ovine pituitary cells with Cx (400 pM) or Cx plus AVP (10 nM) eliminated the adrenocorticotropic hormone (ACTH) secretory response to CRF (10 nM), as assessed 3 days later. Cx alone also reduced the secretory response to AVP from 23.9 +/- 3.4 to 11.5 +/- 1.9 ng ACTH/3 h (P less than 0.05). However, pretreatment with AVP (10 nM) plus Cx caused no further reduction in the secretory response to AVP (10.1 +/- 2.6 ng ACTH/3 h). These data suggest that, if AVP induces erstwhile non-CRF target cells to become CRF targets, then these induced cells are not themselves initially AVP target corticotrophs.