Noradrenergic afferents to median eminence: inhibitory role in rhythmic growth hormone secretion

The involvement of noradrenergic (NA) afferents to the median eminence (ME) in the regulation of growth hormone (GH) secretion was investigated in chronically cannulated, unanaesthetized male rats by using systemically administered 6-hydroxy-dopamine (6-OHDA). One day after 6-OHDA treatment (50 mg/kg, i.v.) GH peak frequency was substantially increased and examination of catecholamine (CA) fluorescence indicated disruption of CA innervation of the ME, but not other central nervous system (CNS) structures. Prolactin secretion at this time was normal and the administration of butaclamol (1.0 mg/kg, i.v.), a dopamine (DA) antagonist, was effective in increasing secretion, indicating that ME DA mechanisms were functionally intact following 6-OHDA treatment. GH secretory patterns returned to normal by 21 days following 6-OHDA treatment and this corresponded with re-emergence of a normal pattern of CA-fluorescence in the ME. In an additional study, the administration of the alpha-NA agonist clonidine (130 microgram/kg, i.v.) increased GH secretion in previously untreated animals. Administration of the alpha-NA agonist oxymetazoline (45 microgram/kg, i.v.), which does not readily pass the blood-brain barrier (BBB), suppressed GH secretion. These findings indicate that ME NA afferents are inhibitory to GH secretion and are a major determinant of the 3 h pattern of GH release in the rat. This inhibitory input is subsidiary to a NA stimulatory input to an as yet unidentified site inside the BBB.