Modulation by thyroid hormones of cytoplasmic estrogen receptor concentrations in reproductive tissues of the rat.

The influence of induced variations in circulating levels of thyroid hormones upon the estrogen receptor content of rat uterine, anterior pituitary and hypothalamic cytosol fractions has been investigated. Sucrose gradient centrifugation analyses showed no observable effects of thyroidectomy or acute induced hyperthyroidism upon receptor levels in uterus hypothalamus of ovariectomized rats, but an apparent positive thyroidal influence upon anterior pituitary receptor content. Qualitatively, the receptor complex sedimentation coefficients were unaltered. Binding assays showed that thyroid hormone administration to the ovariectomized rat resulted in a marked increase in pituitary receptor content, whereas the same treatment had no significant effect on the pituitary receptor level of the intact animal. Conversely, a marked fall in uterine receptor content was found in thyroxine-treated intact, but not castrate, animals. The changes in measurable receptor levels could not be attributed to competition for estrogen binding sites by thyroxine or triiodothyronine. Pituitary receptor content of ovariectomized rats was studied following administration of varying levels of thyroxine; 5 mug/day significantly depressed receptor levels, while enhancement of binding capacity was occasioned by levels of thyroxine ewual to or greather than 25 mug/day. The hypothalamus was completely unaffected by similar treatment and the uterus responded with decreased receptor level only at the highest dosage used. Thyroxine replacement reversed the decrease in anterior pituitary receptor concentration detectable following thyroidectomy. The effect of the thyroid hormones on the pituitary receptor content was not a result of changes in the capability of the tissue to respond to estrogen-induced synthesis of receptor.