Effect of hypothalamic norepinephrine depletion on median eminence CRF-41 content and serum ACTH in control and adrenalectomized rats.

In this study we examined the role of the noradrenergic innervation of the hypothalamus on the adrenalectomy-induced changes in median eminence (ME) CRF-41 and serum ACTH. 6-Hydroxydopamine (6-OHDA), the catecholaminergic neurotoxin, or vehicle was injected into the ventral noradrenergic bundle of male rats. One week later animals underwent adrenalectomy or sham operation and were sacrificed 18 or 120 h later. In sham-operated rats 6-OHDA did not affect ME CRF-41 content or serum ACTH. In vehicle-injected adrenalectomized rats ACTH was increased approximately 3-fold at 18 h and almost 6-fold at 120 h. At 18 h CRF-41 content was markedly depleted (reduced approximately 20-fold) but by 120 h CRF-41 content had partially recovered and was about 70% of control animals. In adrenalectomized animals, 6-OHDA lesions caused a complete inhibition of the increase in serum ACTH both at 18 h and at 120 h. Pretreatment with 6-OHDA partially attenuated the drastic reduction in ME CRF-41 content following adrenalectomy at 18 h. However, at 120 h, the neurotoxin prevented the recovery of CRF-41 following adrenalectomy. These results suggest that intact norepinephrine innervation to the hypothalamus is necessary for the increased production of ACTH following adrenalectomy and that its interruption interferes with both the adrenalectomy-induced ME CRF-41 reduction and subsequent recovery.