Changes in Tuberoinfundibular Dopaminergic Neuron Activity During the Rat Estrous Cycle in Relation to the Prolactin Surge: Alteration by a Mammary Carcinogen

Abstract

An attempt was made to correlate the physiological or the dimethylbenz(a)anthracene (DMBA)-enhanced serum prolactin (PRL) surge, which occurs in the afternoon of proestrus in female Sprague-Dawley (SD) rats, with physiological or pathological changes in two biochemical estimates of the tuberoinfundibular dopaminergic (TIDA) neuron activity. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations as well as tyrosine hydroxylase (TH) activity were measured in the median eminence (ME) of control or DMBA-pretreated SD rats throughout the estrous cycle in relation to PRL secretion. In both groups of females, while the DA content was fairly constant, the DOPAC content and TH activity in the ME fluctuated markedly throughout the estrous cycle. Thus, in control animals, the DOPAC content, DOPAC/DA ratio and TH activity which were stable on the days of diestrus and morning of proestrus were markedly decreased at noon and early afternoon when serum PRL levels began to rise. Later in the afternoon of proestrus, when serum PRL levels were maximal, there was a marked but transient increase in the DOPAC content and DOPAC/DA ratio as well as a brief surge in TH activity. In the evening of the same day, when serum PRL returned to basal levels, the DOPAC content, DOPAC/DA ratio and TH activity were low. Finally on estrus morning, the DOPAC content, DOPAC/ DA ratio and TH activity increased again to reach the diestrus levels. In DMBA-pretreated females, similar fluctuations in TIDA neuronal activity occurred during the estrous cycle, but the dynamics of these changes was altered: the DOPAC/DA ratio and TH activity first showed a marked increase in the morning of proestrus day, before decreasing dramatically. No surge in TH activity was detectable in the afternoon of proestrus and the increase in the DOPAC/DA ratio was of lesser amplitude than that in the controls. In those females whose PRL levels were still higher than those of controls on the morning of estrus, the second increase in the DOPAC/DA ratio was not observed. These results suggest that the lowering in TIDA neuronal activity on the day of proestrus might explain the outset, but not the termination of the preovulatory PRL surge. The regulation involved in the latter process seems to be particularly impaired by DMBA pretreatment.

Stress-Induced Suppression of the Prolactin Afternoon Surge in Ovariectomized, Estrogen-Treated Rats and the Nocturnal Surge in Pseudopregnant Rats Are Accompanied by an Increase in Median Eminence Dihydroxyphenylacetic Acid Concentrations

“…These results indicate that the afternoon estrogen-induced surge of PRL in ovariectomized rats is accompanied by a decrease in the activity of TIDA neurons. These results are consistent with a previous report [19] and suggest that 'disinhibition' of the inhibitory DA tone on PRL secretion during the estrogen-induced PRL surge may be causally related.…”

Prolactin Regulates Tuberoinfundibular Dopamine Neuron Discharge Pattern: Novel Feedback Control Mechanisms in the Lactotrophic Axis

“…To date, this feedback has generally been ascribed to modulating the expression and kinetics of the ratelimiting enzyme in dopamine biosynthesis, tyrosine hydroxylase (TH) (Gonzalez and Porter, 1988;Pasqualini et al, 1988;Voogt, 1991, 1995;Selmanoff et al, 1991). Compared with slow transcriptional and biosynthetic changes, the presumably more rapid electrophysiological effects of Prl on TIDA neurons have yet to be described.…”

Dopaminergic regulation of avian prolactin gene transcription

“…Among them are thyrotropin-releasing hormone (TRH) (Curlewis et al 2002, Kanasaki et al 2002, Yuan & Pan 2002) and the newly described PRL-releasing peptides (Hinuma et al 1998, Curlewis et al 2002. However, PRL release from the anterior pituitary is regulated principally by inhibitory influences imparted by the tuberoinfundibular dopamine (DA) system (Ben-Jonathan et al 1977, Pasqualini et al 1988, Ben-Jonathan & Hnasko 2001. In avian species, the role of DA in regulating PRL secretion is still largely obscure.…”