Thyroid hormones and estrogen affect oxytocin gene expression in hypothalamic neurons.

The oxytocin (OT) gene promoter has a composite hormone response element, such that several members of the steroid/thyroid hormone superfamily of nuclear receptors can interact at this response element in vitro. To investigate this in brain tissue, parallel to foregoing behavioural experiments, we used in situ hybridization histochemistry to seek interactions between estrogen 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 thyroidectomized (TX) in addition to OVX had dramatically elevated levels of OT gene expression in the PVN following EB treatment. That is, endogenous thyroid hormones interfered with EB-induction of gene expression. Moreover, in both OVX and TX/OVX animals, OT gene expression was reduced to values equivalent to controls when T3 was given together with EB. Particular subdivisions of the PVN responded differentially to T3 and EB treatment, demonstrating marked heterogeneity of OT-containing neurons in this nucleus. Thus, parallel to and perhaps related to the manner in which thyroid hormones reduced estrogen-stimulated behaviour, endogenous or exogenous thyroid hormones interfered with estrogen stimulation of OT mRNA. These data demonstrate competition between nuclear proteins, transcription factors, in hypothalamic neurons.