Effects of 6-hydroxydopamine on plasma gonadothrophin levels in male rats

Abstract

<p>A. The involvement of central catecholaminergic neurons in tonic gonadotrophin release in male rats was investigated.</p> <p>(i) Animals were given a single intraventricular injection of 6-hydroxydopamine hydrochloride (6-ODHA; 170 μg free base) dissolved in 0.001 N HCl. Plasma LH and FSH were measured by double antibody radioimmunoassay. LH in the 6-OHDA treated animals was significantly reduced after one hour and remained consistently lower for eight hours. The controls, after a transient elevation, showed no significant change. No difference in LH concentrations was found between experimental groups sampled at two days or later. FSH in treated animals showed less consistent difference from the controls.</p> <p>(ii) Animals given an intraventricular injection of 6-OHDA dissolved in different vehicles, with varied pH and osmolarity, gave similar LH and FSH results which suggests the quinone derivative of 6-OHDA is effective in producing the catecholaminergic impairment.</p> <p>(iii) Administration of 6-OHDA dissolved in different vehicles, with varied pH and osmolarity, gave similar LH and FSH results which suggests the quinone derivative of 6-OHDA is effective in producing the catecholaminergic impairment.</p> <p>These findings indicate the LH release in the male rat may be controlled (or at least modulated) by a central adrenergic mechanism.</p> <p>B. The involvement of the ventral noradrenergic ascending pathway in tonic gonadotrophin release was investigated. Bilateral injection of 6-hydroxydopamine hydrochloride given into the preoptic area of the medial forebrain bundle significantly reduced plasma LH at all times tested. Plasma FSH was not significantly different. These results suggest that tonic LH release is modulated by an extrahypothalamic mechanism.</p> <p>C. The hypothalamic catecholamine content was pharmacologically manipulated with various drugs.</p> <p>(i) An intraperitoneal injection of protriptyline was given before 6-OHDA in order to selectively reduce the hypothalamic content of dopamine. Plasma LH, but not FSH was significantly reduced 3 hours after 6-OHDA in animals pretreated with protriptyline compared to controls. Neither plasma nor testicular testosterone were significantly different between groups.</p> <p>(ii) Animals given DL-threo-dihydroxyphenylserine showed a significant increase in plasma LH (previuosly decreased by 6-OHDA) compared to controls. DL-threo-dihydroxyphenylserine selectively restores the noradrenaline content in the hypothalamus.</p> <p>(iii) γ-Butyrolactone blocks the central release of dopamine and produces anaesthesia resembling deep sleep. No consistent significant differences were found in either plasma LH or FSH at any of the times or doses tested in animals given either γ-butyrolactone or a metabolite, γ-hydroxybutyric acid, compared to the control group receiving saline injection alone.</p> <p>(iv) 6-hydroxydopa which selectively reduces brain noradrenaline content, had no effect on plasma LH and FSH.</p> <p>The above findings give further support to the concept of modulation of tonic gonadotrophin release by an extrahypotalamic noradrenergic mechanism.</p>