Interaction of thyroxine and estrogen on the expression of estrogen receptor alpha, cholecystokinin, and preproenkephalin messenger ribonucleic acid in the limbic-hypothalamic circuit.

To study thyroid hormone and estrogen interactions in the central nervous system (CNS), the expression of estrogen sensitive genes was examined within the limbic-hypothalamic circuit. Estrogen up-regulates the expression of reproductively relevant neuropeptide messenger RNAs (mRNAs) encoding cholecystokinin (CCK) and enkephalin, peptides that stimulate lordosis. Estrogen down-regulates the expression of the estrogen receptor alpha (ER alpha) mRNA in the nuclei of the circuit. We examined the possibility that thyroid hormone treatment would block the estrogen modulation of these messages. Estradiol benzoate (EB), EB + thyroxine (T4), T4, or oil were administered to ovariectomized, adult female rats for 10 days. Isotopic in situ hybridization histochemistry revealed that within the limbic-hypothalamic nuclei, levels of CCK and preproenkephalin (PPE) mRNA levels were significantly higher in EB and EB + T4-treated animals compared with T4 or oil-treated animals. ER alpha mRNA levels were low in EB treated animals, elevated in T4 or oil-treated animals and further elevated in EB + T4-treated animals. In summary, T4 treatment had neither an independent nor an antagonistic effect on estrogen induced expression of CCK or PPE mRNA in the circuit. However, T4 did prevent the normal estrogenic decrease of ER alpha mRNA levels in the nuclei of the limbic-hypothalamic circuit.