Effect of axonal transport blockade on corticotropin-releasing factor immunoreactivity in the median eminence of intact and adrenalectomized rats: relationship between depletion rate and secretory activity.

Male Wistar rats were anaesthetized, injected intracisternally (i.c.) with saline or colchicine and were decapitated at various time intervals. Trunk blood was collected for the determination of immunoreactive adrenocorticotropic hormone (ACTHi) by radioimmunoassay (RIA) and of corticosterone by a fluorometric assay. Changes in corticotropin-releasing factor (CRF) content of the median eminence (ME) were assessed by quantitative immunocytochemistry (QICC) on cryostat sections of ME preparations or by RIA of CRF in ME-extracts. Administration of colchicine resulted in a long-lasting and dose-dependent stimulation of ACTHi secretion. At a dose of 25 micrograms, high plasma ACTHi levels were found for up to 24 h. A dose of 5 micrograms per rat, that has been reported to effectively block vasopressin transport in paraventricular-neurohypophyseal neurons, resulted in a small elevation of plasma ACTHi. In intact rats, i.c. administration of saline of saline containing 5 micrograms of colchicine had no effect on the CRF content in the ME. In contrast, colchicine caused a depletion of the CRF stores in the ME of 1-week adrenalectomized (ADX) rats. The disappearance rate was 9.2%/h as measured by RIA and 11.2%/h as measured by QICC. When plasma corticosterone and ACTHi were normalized by giving ADX rats corticosterone in drinking water, the colchicine-induced depletion of the CRF stores was fully prevented. We conclude that the rate of decline of CRF in the ME of rats treated with a non-toxic dose of colchicine to block axonal transport is positively correlated to the secretory activity of CRF neurons of the paraventricular-infundibular system.