Developmental regulation of tyrosine hydroxylase in the mediobasal hypothalamus

In the adult rodent the mediobasal hypothalamus (MBH) interacts extensively with the pituitary gland to regulate a variety of endocrine functions. The dopaminergic (DA) neurons of the mature MBH are influenced by numerous transmitters and hormones, however, little is known about developmental regulation of this system. Ontogeny of DA neurons was examined in vivo and in explant culture by monitoring tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. The influence of the depolarizing agent, veratridine, was examined to determine whether development of TH in the MBH is regulated by depolarizing signals as in other CA neurons. Veratridine elicited a significant increase in TH activity in cultures of MBH. Adult MBH neurons are influenced by hormones such as estradiol. We investigated the possible role of estradiol in regulating the ontogeny of MBH DA neurons in culture. We developed a steroid-depleted culture medium to rigorously define the effects of steroids on the developing system. This enabled us to determine that estradiol does not appear to influence TH during embryonic development, though estrogen receptors are present at this stage. These results were confirmed in vivo by injecting neonates with moxestrol, a synthetic estrogen which is not sequestered by alpha-fetoprotein. This treatment did not elicit any change in TH. Our observations suggest that although estrogen regulates TH in the adult MBH, this hormone does not play a role in developmental regulation of TH in this brain region. In contrast, however, depolarizing signals appear to be a widespread mechanism for regulation of TH in numerous neuronal populations.