Suppressed tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic system during lactation

Suckling-induced PRL secretion is regulated in part by a reduction in tuberoinfundibular dopamine (TIDA) neuronal activity. We have examined the effects of suckling on TIDA activity in the arcuate nucleus by measuring changes in gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. TH gene expression was assessed by performing in situ hybridization, using a 35S-labeled antisense riboprobe for quantitating TH mRNA and analyzing grain density with the aid of an Optimas Bioscan image analysis system. Lactating rats suckled by eight pups were studied on postpartum day 10, and diestrous day 1 rats were used as controls. The results showed that lactation suppressed TH mRNA content throughout the arcuate nucleus to about 10% of diestrous levels. The dramatic reduction in TH mRNA during lactation was specific to the arcuate nucleus, as TH mRNA levels in the zona incerta were similar during lactation and diestrus. The suckling stimulus was the primary signal responsible for the suppression of TH mRNA in the arcuate nucleus, as removal of the pups for 6 h restored TH mRNA content to diestrous levels. By 24 h after pup removal, TH mRNA had reached almost twice diestrous levels. In view of the dramatic reduction in TH mRNA levels during lactation, we examined whether TH protein in the arcuate nucleus was similarly diminished. TH protein was detected by immunocytochemistry using a monoclonal antibody to TH. Qualitatively, TH staining was heavier in cell bodies, nerve fibers, and median eminence during diestrus. There was a small, but significant, decrease in TH-positive cell numbers during lactation (14% reduction) compared to those on diestrus. These data provide clear evidence that TH expression is suppressed during lactation, as evidenced by the decrease in TH mRNA and TH protein. The reduction in TH expression most likely contributes to the decrease in dopaminergic tone during lactation.