Prolactin-Induced Activation of Tuberoinfundibular Dopaminergic Neurons: Evidence for Both a Rapid ‘Tonic’ and a Delayed ‘Induction’ Component

Publisher Website
Google Scholar
Abstract
Results of previous studies have revealed that prolactin causes a delayed (12–16 h) increase in the rate of synthesis and turnover of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence. Attempts to demonstrate a rapid in vivo action of prolactin on these neurons has been frustrated because pharmacological manipulations needed to make the biochemical measurements of TIDA neuronal activity (i.e., administration of α-methyl-tyrosine or NSD 1015) inhibit DA synthesis and thereby remove the tonic inhibitory control of DA on prolactin secretion. Thus, ‘control’ rates of synthesis and turnover of DA in terminals of TIDA neurons are actually values obtained in the presence of high circulating concentrations of prolactin. Results of the present in vivo studies demonstrate that there are two components to the activation of TIDA neurons by prolactin: a rapid ‘tonic’ component, which is responsive to acute changes in prolactin concentrations, and a delayed ‘induction’ component, which is activated by long-term changes in prolactin concentrations. Experimental observations which support this proposal are described below. Hypophysectomy or treatment with bromocriptine (a DA agonist) reduce circulating levels of prolactin and reduce the rate of DA synthesis in the median eminence. Intracerebroventricular (i.c.v.) administration of prolactin to these animals increases the rate of DA synthesis in the median eminence within 4 h (rapid ‘tonic’ component) and then causes a further increase after 12 h (delayed ‘induction’ component); only the latter component is blocked by treatment with cycloheximide, indicating the involvement in protein synthesis. In addition, the delayed ‘induction’ component of the feedback activation of TIDA neurons represents a change in the capacity of the rapid ‘tonic’ component since the delayed effect is observed only if the TIDA neurons are exposed to prolactin for a brief period prior to the time that measurements of DA synthesis rates are made. This is exemplified by the fact that the increased rate of DA synthesis in the median eminence observed after circulating concentrations of prolactin have been elevated for 16 h by the administration of a large dose of haloperidol (1 mg/kg) can be prevented if the prolactin levels are reduced by bromocriptine 4 h prior to measurement. In turn, this action of bromocriptine can be reversed by the i.c.v. administration of prolactin 4 h prior to measurement. Furthermore, a low dose of haloperidol (0.1 mg/kg), which increases prolactin at 1 h but not at 16 h, does not increase DA synthesis in the median eminence at 16 h (delayed component). However, if a second injection of this same low dose of haloperidol is administered at 12 h, the rate of DA synthesis at 16 h is increased to the same degree as the larger dose of the DA antagonist. Thus, at any point in time, the activity of TIDA neurons appears to be influenced by the circulating concentration of prolactin at the time of measurement (rapid ‘tonic’ component) and by the previous patterns of serum prolactin concentrations (delayed ‘induction’ component).