Thyroid hormones and estrogen affect oxytocin gene expression in hypothalamic neurons

The oxytocin (OT) gene promoter has a composite hormone response element, s uch that several members of the steroid/thyroid hormone superfamily of nucl ear receptors can interact at this response element in vitro. To investigat e this in brain tissue, parallel to foregoing behavioural experiments, we u sed in situ hybridization histochemistry to seek interactions between estro gen and thyroid hormones on OT mRNA in the hypothalamus. In ovariectomized (OVX) rats, high doses of triiodothyronine (T3) elevated OT mRNA levels in the paraventricular (PVN) nucleus, while treatment with estradiol benzoate (EB) alone had no significant effect, in contrast, animals that were thyroi dectomized (TX) in addition to OVX had dramatically elevated levels of OT g ene expression in the PVN following EB treatment. That is, endogenous thyro id hormones interfered with EB-induction of gene expression. Moreover, in b oth OVX and TX/OVX animals, OT gene expression was reduced to values equiva lent to controls when T3 was given together with EB. Particular subdivision s of the PVN responded differentially to T3 and EB treatment, demonstrating marked heterogeneity of OT-containing neurons in this nucleus. Thus, paral lel to and perhaps related to the manner in which thyroid hormones reduced estrogen-stimulated behaviour, endogenous or exogenous thyroid hormones int erfered with estrogen stimulation of OT mRNA. These data demonstrate compet ition between nuclear proteins, transcription factors, in hypothalamic neur ons.