Hyperprolactinemia Increases and Hypoprolactinemia Decreases Tyrosine Hydroxylase Messenger Ribonucleic Acid Levels in the Arcuate Nuclei, but not the Substantia Nigra or Zona Incerta*

Abstract

The effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase (TH) mRNA signal levels were examined in dopaminergic neurons ovariectomized rats. TH mRNA signal levels and relative TH quantity in the arcuate nuclei, zona incerta, and substantia nigra were evaluated by in situ hybridization and immunocytochemistry, respectively. The catalytic activity of TH in the stalk-median eminence (SME) was determined from the in vitro rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine. Chronic administration of bromocriptine (BROMO), a dopamine (DA) agonist, for 3 days reduced circulating rat PRL (rPRL) levels compared to those in the vehicle-treated controls. BROMO treatment decreased TH mRNA signal levels in the arcuate nuclei, the intensity of TH immunostaining in the arcuate-median eminence area, and the rate of DOPA accumulation in the SME. Concomitant administration of ovine PRL (oPRL) reversed the effects of BROMO on TH, resulting in markedly increased TH mRNA signal levels, intensity of TH immunostaining, and rate of DOPA accumulation. Treatment with oPRL by itself for 3 days increased TH mRNA signal levels in the arcuate nuclei and TH activity in the SME, compared to vehicle. Chronic treatment with haloperidol, a DA antagonist, increased circulating levels of endogenous rPRL and increased TH activity in the SME to values similar to those after oPRL treatment. However, in contrast to oPRL, mRNA levels in the arcuate nuclei of haloperidol-treated rats were similar to levels in vehicle-treated animals. To evaluate whether the effect of PRL on TH was species specific, oPRL or rPRL was continuously infused into the jugular vein using an osmotic minipump. TH mRNA levels in the arcuate nuclei were elevated above control levels by either oPRL or rPRL administration. TH mRNA levels in the DA perikarya located in the zona incerta and substantia nigra were not altered by treatment with a DA agonist, a DA antagonist, or PRL. These results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment, respectively, TH mRNA levels in the tuberoinfundibular dopaminergic neurons. The alterations in TH mRNA content probably contribute to the decrease or increase in TH activity associated with hypoprolactinemia or hyperprolactinemia, respectively.