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Estradiol and tamoxifen interactions with thyroid hormone in the ovariectomized-thyroidectomized rat
V A DiPippo1, R Lindsay, C A Powers
1Department of Pharmacology, New York Medical College, Valhalla 10595.
Endocrinology
|March 1, 1995
Summary
Estrogen and thyroid hormone (T3) receptors may interact, influencing physiological responses like growth and metabolism. This study in rats suggests receptor cross-talk affects hormone actions in vivo.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Estrogen and thyroid hormone (T3) receptors share similar DNA-binding domains and target sequences.
- In vitro studies suggest potential competition (cross-talk) between estrogen and T3 receptors for DNA binding.
- Lack of in vivo physiological studies to confirm receptor cross-talk between estrogens and T3.
Purpose of the Study:
- To investigate in vivo physiological evidence of cross-talk between estrogen and T3 receptors.
- To determine if estrogens can mimic or inhibit T3 actions, and vice versa, through receptor interactions.
- To evaluate the effects of estradiol, tamoxifen, and T3 in a controlled rat model.
Main Methods:
- Utilized an ovariectomized-thyroidectomized rat model to minimize confounding neuroendocrine and pharmacokinetic interactions.
- Administered estradiol, tamoxifen (antiestrogen), and T3 to assess their effects on specific hormone-regulated responses.
- Monitored T3 responses (GH, somatic growth, malic enzyme, TSH) and estrogen responses (pituitary kallikrein, PRL, uterine weight, triglycerides, LH).
Main Results:
- Estradiol and tamoxifen exhibited partial T3 agonist/antagonist effects on growth hormone (GH) induction and pure antagonism on somatic growth and hepatic malic enzyme induction.
- Estradiol inhibited T3-induced decreases in bone mineral density, while T3 partially mimicked estrogen's suppression of luteinizing hormone (LH).
- Estrogen and tamoxifen increased serum triglycerides in a T3-dependent manner, despite T3's tendency to decrease triglycerides.
Conclusions:
- Physiological effects of estrogens on GH, growth, bone, malic enzyme, and triglycerides suggest cross-talk with T3 receptors in vivo.
- Tamoxifen mimicked estradiol's effects by antagonizing T3 actions but acted as an antiestrogen for other responses.
- Evidence supports a physiological mechanism involving estrogen and T3 receptor cross-talk influencing multiple endocrine pathways.