Effects of neurotransmitters on the release of corticotropin releasing hormone (CRH) by rat hypothalamic tissue in vitro

Summary Effects of neurotransmitters on in vitro release of CRH from rat hypothalamic tissue were investigated. Three whole hypothalami or three mediobasal hypothalami from male rats, adrenalectomized 7 days before, were incubated for 10 min in a medium similar to cerebrospinal fluid at 37 ° C under 95% O₂, 5% CO₂. CRH activity was assayed by radioimmunological measurement of ACTH released by isolated pituitary cells from adrenalectomized rats.Norepinephrine (NE) at a concentration of 0.02×10^–6 M to 2×10^–6 M stimulated dose-related CRH release. At larger concentrations the response decreased again (bell-shaped dose-response relationship). The action of norepinephrine was completely blocked by coincubation with phentolamine. Similar results were obtained whether whole hypothalami or mediobasal hypothalami were incubated with norepinephrine. This suggests that the site of action of NE was within the mediobasal hypothalamus. The possibility that the observed effects were due to the CRH-like activity of vasopressin released from the hypothalamic tissue was excluded by simultaneous measurements of CRH activity and arginine-vasopressin concentrations in the medium. Dopamine at very large concentrations (17.6×10^–6 M) also stimulated CRH release. Acetylcholine, serotonin, histamine and GABA did not influence the basal CRH release at any of the concentrations tested.These results suggest that in the rat, norepinephrine may have a physiological role as stimulator of CRH-release at the level of the mediobasal hypothalamus. However, in view of the conflicting results obtained with similar and other methods, no definite conclusions should yet be drawn.This work was supported by Deutsche Forschungsgemeinschaft. Bonn-Bad Godesberg. SFB 87/B2. K.H. V. is a recipient of a Heisenberg Stipendium