Sex-Related Alterations in Hypothalamic Tyrosine Hydroxylase after Neonatal Monosodium Glutamate Treatment

Abstract

This study compared tyrosine hydroxylase (TH) mRNA signal levels, relative quantity of TH protein, and the catalytic activity of TH in the tuberoinfundibular dopaminergic neurons (TIDA) of male and ovariectomized (OVEX) female rats. In addition, the effects of monosodium glutamate (MSG) neurotoxicity on these parameters of TH regulation were evaluated. Neonatal rats were injected with MSG (4 mg/g body weight) or 10% sodium chloride (controls) on alternate days for the first 10 days of life. Females were ovariectomized on day 45 of age, and all rats were used between 60 and 80 days of age. The TH mRNA signal levels, as assessed by an in situ hybridization technique, were 2-fold higher in control females than in control males, whereas the number of TH mRNA-containing cells was similar between sexes. The TH immunostainings of the TIDA perikarya in the arcuate nucleus and of the nerve terminals in the median eminence were qualitatively more intense in females than males. The catalytic activity of TH, as determined by in vitro DOPA accumulation in the stalk-median eminence, was 3-fold greater in females than males. Neonatal MSG-treatment resulted in a marked reduction in the number of TH mRNA-containing cells and TH-immunopositive cells in the arcuate nucleus of both sexes, as well as a decrease in the intensity of TH immunostaining in the median eminence. The cellular mRNA signal levels for TH were markedly reduced in females after MSG treatment, but were unchanged in males. MSG treatment reduced TH activity to 20% of control levels in females, but did not alter enzyme activity in males. Serum PRL levels were 3-fold higher in intact males than in OVEX females, but were not changed after MSG treatment in either sex. The PRL and protein contents of the anterior pituitary were reduced similarly, by 50–60%), in both female and male rats. These data suggest that a greater expression of the TH gene may, in part, account for the higher TH activity in the TIDA neurons of control female versus control male rats. Furthermore, a stimulatory input in initiating or maintaining cellular TH mRNA levels in the TIDA neurons is functionally disrupted by MSG treatment in female rats, but not in male rats. Aspects of TH regulation other than mRNA levels, possibly the activation state of the enzyme, may be altered in male rats after MSG treatment to maintain TH activity similar to that found in control males, in spite of the reduction in total TH mRNA levels. The lack of any change in plasma PRL levels in the adult rat treated neonatally with MSG suggests that alterations in dopaminergic neuronal function are not always inversely related to circulating PRL levels.