Corticotropin-Releasing Factor Levels in the Peripheral Plasma and Hypothalamus of the Rat Vary in Parallel with Changes in the Pituitary-Adrenal Axis*

Impressive evidence has emerged indicating that immunoassayable and bioassayable CRF, which is immunoneutralizable, is present not only in the hypothalamus but in many peripheral tissues as well. Using highly specific and sensitive RIAs and immunoaffinity chromatography to investigate whether this extrabrain CRF circulates in the rat, we found low but clearly measurable levels in peripheral plasma (mean, 11.4 +/- 0.8 pg/ml). Immunological findings were corroborated by fast protein liquid chromatography, which resolves peptides by both hydrophobicity and ionic charge. With this approach the major immunoreactive peak was eluted at the position of synthetic rat CRF standard. To assess whether levels of peripheral plasma CRF-like immunoreactivity (CRF-LI) vary in parallel with those of hypothalamic CRF-LI, we performed studies with low and high dose dexamethasone administration and withdrawal, adrenalectomy, and hypophysectomy. Seven days after oral administration of dexamethasone, there was a decrement in the levels of peripheral plasma and hypothalamic CRF-LI. Depending on the dose, recovery was also found 7 days after cessation of the treatment. After either adrenalectomy or hypophysectomy, there were increments in the levels of CRF-LI in both peripheral plasma and hypothalamus. Thus, concentrations of CRF-LI in the peripheral plasma and in the hypothalamus vary in parallel in response to alterations in the pituitary-adrenal axis.