A PHYSIOLOGICAL-ROLE FOR SPORADIC INTERRUPTIONS OF THE DOPAMINERGIC TONE IN THE GENESIS OF BIG MASS PROLACTIN PULSES

The present studies were designed to evaluate pulsatile PRL secretion after the establishment of either a continuous dopaminergic input or a complete blockade of the dpaminergic inhibitory tone. Adult female rats on estrus and male rats implanted with indwelling jugular cannulae were bled at 3-min intervals for a 3-h period. Bromocriptine (CB-154) and domperidone (DOM) were administered sc and iv, respectively. The administration protocol used for both treatments produced either a continuous dopaminergic input (CB-154 treatment) or a complete dopaminergic blockade (DOM treatment). Pulse analysis was performed on the data series using the algorithm Detect. In both estrous female and male rats, dopaminergic receptor activation by CB-154 reduced peak and trough values, pulse amplitude, area under the pulse, and mean PRL levels. In contrast, a complete dopamine (DA) receptor blockade by DOM increased these parameters. Domperidone treatment increased pulse frequency and reduced pulse interval and duration. Bromocriptine, however, differentially affected some pulsatility parameters depending on the sex of the rats. In females, CB-154 did not alter any of the qualitative parameters (frequency, pulse interval, and duration) of pulsatile PRL secretion. In contrast, in male rats the treatment reduced frequency and duration while increasing pulse interval. CB-154 reduced basal PRL levels in male rats, whereas in estrous females this parameter was not altered. PRL pulses were further evaluated by frequency distribution analysis, using the area under the pulses divided by the baseline to normalize the data due to treatment-induced differences in baselines. This calculation allows the estimation of the amount of hormone released per pulse over the baseline. In both estrous female and male rats, two classes of PRL pulses were identified. One class corresponded to pulses containing a small mass of hormone [small mass pulses (SM)], while the others were characterized by pulses containing a large mass of hormone [big mass pulses (BM)]. Interestingly, both the dopaminergic agonist CB-154 and the dopaminergic antagonist DOM dramatically diminished BM pulse incidence in both estrous female and male rats. In fact, BM pulses were practically absent in both experimental groups. To further substantiate this notion, animals of each experimental group were assigned to one of the following categories: animals depicting BM and SM pulses or rats presenting solely SM pulses. Statistical analysis using Fisher's test demonstrated that both treatments significantly reduced the number of animals showing both BM and SM pulses, reinforcing the idea that both treatments changed the physiological pattern, i.e. presence of both BM and SM pulses, to a pattern characterized by the presence of only SM PRL pulses. This study indicates that DA is an important inhibitory regulator of pulsatile PRL secretion. The results demonstrate that BM PRL pulses originate from a discontinuous inhibitory dopaminergic tone. This is based on the observation that BM PRL pulses are suppressed by either continuous blockade or activation of the dopaminergic input. SM PRL pulses appear to be DA independent and, thereby, mediated by stimulatory neural inputs that are able to induce PRL secretion even in the presence of a continuous and strong dopaminergic tone.