Corticotropin Releasing Factor Distribution in Normal and Brattleboro Rat Brain, and Effect of Deafferentation, Hypophysectomy and Steroid Treatment in Normal Animals

Abstract

Corticotropin-Releasing Factor (CRF) activity was determined (dispersed pituitary cell assay) in rat median eminence (ME), various hypothalamic nuclei, as well as in entire median basal hypothalamus (MBH) and extra-hypothalamic areas. Highest concentrations were seen in ME, with decreased concentrations noted proceeding dorsally and cephalad from ME. Potency (NIAMDD HE-RP-1, ME reference extract, equivalent to 1.0) estimates were: ME-2.2; arcuate n.-0.88; dorsomedial n.-041; ventromedial n.-0.35; periventricular n.-0.24; hypothalamus-0.05; thalamus-0.01; cortex-0.005. Measurable, but lesser amounts, than in the above cited nuclei, were present in supraoptic and paraventricular nuclei. CRF activity was not measurable in preoptic area, septum, olfactory bulb, striatum, mesencephalon, pons, medulla or cerebellum. Complete hypothalamic deafferentation was accompanied by an increase in CRF activity/mug protein in ME and MBH, associated with decreased AM plasma ACTH and corticosterone concentrations. CRF-like activity in ME and MBH increased following hypophysectomy and after dexamethasone pretreatment. These findings indicate that CRF is mainly synthesized in the ME and surrounding area, and this source of CRF is sensitive to feedback effects and that extrahypothalamic inputs affect CRF release. Female animals had higher ME CRF content than did male animals. Homozygous and heterozygous Brattleboro rats had significantly less CRF in ME and MBH than did control animals, with significant differences also noted between homozygous and heterozygous animals.