Circulating Corticotropin Releasing Factor-Like Activity in Man

Abstract

To investigate the possible existence of corticotropin releasing factor (CRF)-like activity in human plasma, methanol extracts of plasma were incubated with rat anterior pituitary tissue in vitro and ACTH release was determined. The extracts were reconstituted so that 1.0 ml was equivalent to 20 ml of original plasma, and the following doses in 5.0 ml incubation volumes elicited a stepwise increase in ACTH release: 100, 250, 500 and 750 .mu.l. The 250, 500, and 750 .mu.l doses resulted in a linear log dose-response. Parallel experiments with 0.5, 1, 2, 5 and 10 rat hypothalamic equivalents in 5.0 ml incubation volumes resulted in a similar stepwise increase in ACTH release. Control experiments indicated a significantly greater ACTH release when pituitary tissue was incubated with methanol extracts of rat hypothalami in comparison to hypothalami added directly in vitro, validating the methanol extraction technique with a known source of CRF. Ultrafiltration experiments with the human plasma CRF-like activity suggest a MW larger than 10,000 daltons.