Most of the corticotrophin-releasing factor (CRF) activity of normal rat median eminence (ME) extract binds to a neurophysin affinity column. The bound material contains the large and small factors, which we have previously demonstrated to be required together for full activity. Most of the CRF activity of Brattleboro rat ME extract, which contains as much CRF activity as the ME extract of a normal rat, does not bind to a neurophysin affinity column. The CRF activity of Brattleboro rat ME extract resides entirely in a large molecule as determined by Sephadex G-25 chromatography. The different properties of Brattleboro and normal rat CRF suggest that the CRF activity in the Brattleboro rat may result from a substance which is different from that in a normal rat.

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