Age-Related Loss of the Responsiveness of the Tuberoinfundibular Dopaminergic Neurons to Prolactin in the Female Rat

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Abstract
In the old female rat the previous findings of a sustained reduction of the secretory activity of the hypothalamic tuberoinfudibular dopaminergic (TIDA) neurons associated associated with a persistent hyperprolactinemia as well as the observation of a failure of the prolactin (PRL) short-loop feedback mechanism have been suggestive of an age-related loss of the responsiveness of the TIDA neurons to the stimulatory action of PRL. Yet the existence of significant impairments in the capacity of the neurons to respond to PRL could not be demonstrated in an earlier study using multiparous old rats in constant estrus compared to young nulliparous estrous rats. In the present study we have readdressed the issue using nulliparous old rats (24-26 months) compared to virgin young rats (4-5 months); two sets of old rats were studied which displayed distinct senile reproductive states, namely persistent diestrus or repetitive pseudopregnancy, and they were compared to young rats in diestrus or in repetitive pseudopregnancy, respectively. The secretory activity of the TIDA neurons was evaluated by measurement of dopamine biosynthesis in the neurons (DOPA accumulation in the median eminence after decarboxylase inhibition) and dopamine release into hypophysial portal blood, and PRL influence on the activity of the TIDA neurons was studied after repeated s.c. administrations of ovine PRL (oPRL) or the solvent vehicle. A reduced activity of the TIDA neurons was observed in both groups of nulliparous aged rats compared to their respective young control group. As for PRL regulation of the TIDA neurons, a significant increase of the activity of the neurons was found in both groups of young rats (diestrous and pseudopregnant) whereas no effect of PRL treatment was observed on the activity of the neurons in the aged rats. Furthermore, the effects of oPRL treatment on PRL circulating plasma levels were tested in the young and old diestrous rats; oPRL treatment was accompanied by a decrease in PRL circulating levels in young rats whereas the typical hyperprolactinemia found in the old rats was not influenced by oPRL treatment. The present results are, therefore, supportive of a loss of the responsiveness of the TIDA neurons to PRL in old female rats and they are suggestive of age-related alterations in PRL receptors in the hypothalamus. The apparent discrepancy between our observations and previous reports may be attributed to differences in the reproductive state of the aged rats and particularly to multiparity, a documented influential parameter in aging processes.