Effect of hormonal interaction on desensitization of the adrenocorticotropin response to arginine vasopressin in ovine anterior pituitary cells
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are major physiological stimulators of adrenocorticotropin (ACTH) secretion from the pituitary gland, while glucocorticoids act as inhibitors. In addition to acting alone, CRH, AVP and glucocorticoids interact with each other to regulate ACTH release in response to stress. Prolonged or repeated stimulus results in attenuated ACTH responsiveness, a process termed as desensitization. The aim of this study was to investigate the effects of interactions between CRH, AVP and steroids on desensitization of the ACTH response to AVP. Perifused ovine anterior pituitary cells were stimulated with three 5-min pulses of 100 nM AVP at 120, 200 and 280 min, and were continuously exposed to CRH (0.2 nM) from 80 min and/or cortisol (10-500 nM) from 0 min onwards. Desensitization was induced by a 15 min pre-treatment with 5 nM (0.5 nM for CRH alone) AVP immediately preceding the second AVP pulse. When CRH was absent, pre-treatment with 0.5 nM AVP did not influence the ACTH response to the second AVP pulse. In the presence of CRH, the response to the second AVP pulse was reduced to 66.7±2.2% of control (n=6, P<0.0001, t-test). On the other hand, following 5 nM AVP pre-treatment, continuous perifusion with cortisol (100 nM) results in a significantly smaller reduction in the response to the second AVP pulse compared with that seen in its absence (78.4±1.7% c.f. 66.7±1.9% of control; n=10, P<0.001, t-test). In contrast to this, following 5 nM AVP pre-treatment, continuous CRH and cortisol in combination results in a greater reduction in the response to the second AVP pulse compared with that obtained in the absence of these two hormones (46.5±1.7% c.f. 66.2±1.7 of control; n=8, P<0.0001, t-test). Taken together, these data suggest that desensitization of the ACTH response to AVP can be modulated by CRH and/or cortisol: CRH or CRH and cortisol in combination amplify this desensitization, whereas cortisol reduces it.