Premium
Negative Feedback by Corticosterone is the Major Mechanism Responsible for Corticotropin‐Releasing Factor‐Induced Desensitization
Author(s) -
Miyanaga Ken,
Miyabo Susumu,
Ooya Eiichi
Publication year - 1990
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1990.tb00649.x
Subject(s) - desensitization (medicine) , endocrinology , medicine , corticosterone , mechanism (biology) , corticotropin releasing hormone , negative feedback , psychology , receptor , hormone , philosophy , physics , epistemology , quantum mechanics , voltage
Subcutaneous infusion of ovine corticotropin‐releasing factor (oCRF) to male rats at a rate of 0.1 μg/h for 4 days did not alter the rise of plasma adrenocorticotropin (ACTH) and corticosterone induced by 3‐min ether exposure. In contrast, 1.0 μg/h oCRF for 4 days virtually abolished the ACTH response to ether, whereas a substantial corticosterone response was preserved. Intravenous administration of phenoxybenzamine (5 mg/kg) prior to ether stress completely inhibited the corticosterone response. Plasma ACTH and corticosterone responses in chronic CRF‐treated rats to an intravenous bolus injection of 2.0 μg oCRF were also markedly blunted by pretreatment with subcutaneous oCRF 1.0 μg/h for 4 days. Adrenalectomized rats given corticosterone in the drinking fluid at a concentration of 80 μg/ml showed a plasma corticosterone pattern mimicking the normal diurnal rhythm. Basal plasma ACTH and thymus weight were within normal limits. In these rats, the magnitude of ACTH rise to ether stress did not differ between the chronic CRF‐treated rats and the vehicle‐treated rats. In cultured pituitary cells prepared from animals infused with oCRF 1.0 μg/h for 4 days, the basal and CRF‐stimulated ACTH release was reduced by 46%. We conclude that among the possible mechanisms proposed for ‘desensitization’ during long‐term infusion of CRF, negative feedback by elevated corticosterone at both brain and pituitary levels is the primary factor. The results also suggest the existence of non‐ACTH‐mediated catecholaminergic systems in the stress‐induced adrenocortical activation.