Ontogeny of tyrosine hydroxylase mRNA signal levels in central dopaminergic neurons: development of a gender difference in the arcuate nuclei

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Using in situ hybridization and immunocytochemistry, this study examined the tyrosine hydroxylase (TH) mRNA signal levels and immunostaining in the arcuate nuclei of the hypothalamus, zona incerta and substantia nigra of male and female rats during neonatal, peripubertal and adult life. The catalytic activity of TH in the stalk-median eminence was also investigated using the in vitro accumulation of 3,4 dihydroxyphenylalanine (DOPA) after inhibiting aromatic amino acid decarboxylase activity. In the arcuate nuclei, TH mRNA levels increased 3.5-fold between 5 and 15 days of age and remained at a steady level between 15 and 35 days of age in both male and female rats. Similar to TH mRNA levels in the arcuate nuclei, TH activity in the stalk-median eminence increased 2-3 fold between days 10 and 15 of age and remained at a steady level between 15 and 35 days of age in both sexes. A later increase in TH mRNA levels in the arcuate nuclei and catalytic activity in the stalk-median eminence was observed between 35 and 40 days in females, but not males. During adulthood, TH mRNA levels and enzyme activity were 2.7-fold higher in the arcuate nuclei and stalk-median eminence, respectively, of diestrous females vs males. These data suggest that the changes in TH mRNA in the arcuate nuclei may contribute to the developmental alterations, as well as the adult gender differences, in enzyme activity in the stalk-median eminence. Circulating progesterone levels were low (1-10 ng/ml) between days 5 and 25 of age and increased 6-fold between 25 and 35 days of age in both males and females. Progesterone levels increased 2-fold in females, but not males, between days 35 and 40 and were 4-fold higher in diestrous females as compared to adult males. Circulating prolactin levels were low (2-3 ng/ml) between days 5 and 15, increased 15-fold between days 15 and 25 and increased an additional 2- to 3-fold between days 35 and 70 in both males and females. TH mRNA signal levels increased between days 5 and 15 of age in dopaminergic perikarya in the zona incerta and the substantia nigra of both female and male rats. The TH mRNA levels remained constant between days 15 and 70 in the zona incerta, whereas TH mRNA levels declined with age in the substantia nigra.(ABSTRACT TRUNCATED AT 400 WORDS)