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Thyroid hormone is an inhibitor of estrogen-induced degradation of estrogen receptor-alpha protein: estrogen-dependent proteolysis is not essential for receptor transactivation function in the pituitary

Thyroid hormone is an inhibitor of estrogen-induced degradation of estrogen receptor-alpha protein: estrogen-dependent proteolysis is not essential for receptor transactivation function in the pituitary

Endocrinology 144(8): 3469-3476

Proteolysis by the 26S proteasome is an important regulatory mechanism that governs the protein stability of several steroid/nuclear receptors and that has been implicated in the control of receptor transcriptional activation function. Herein, we report that thyroid hormone can prevent estrogen-induced proteolysis of estrogen receptor-alpha (ERalpha) protein in lactotrope cells of the pituitary. The stabilization of ERalpha protein by thyroid hormone represents a selective blockade against estradiol-stimulated degradation, because thyroid hormone (but not glucocorticoid) can protect estrogen-activated ERalpha. Moreover, thyroid hormone treatment does not interfere with signal-induced proteolysis of a separate proteasome target, IkappaBalpha or ERalpha proteolysis induced by ICI182780. Using thyroid hormone as a tool to inhibit ERalpha proteolysis, we examined the effect of loss of this regulatory function on estrogen-induced transcriptional responses. Consistent with earlier reports, estrogen activation of an idealized estrogen response element reporter gene was inhibited. However, thyroid hormone did not prevent induction of prolactin gene expression or the ability of ERalpha to stimulate proliferation. These results demonstrate that estrogen-induced proteolysis of ERalpha is not a general requirement for receptor transcriptional activation function, and they demonstrate that proteolytic regulation is a means by which other endocrine factors can indirectly modulate ERalpha activity.

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Accession: 011569194

Download citation: RISBibTeXText

PMID: 12865327

DOI: 10.1210/en.2002-0092

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