From Estrogen to Androgen Receptor: a New Pathway for Sex Hormones in Prostate

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1998 May 20

PMID 9576916

Citations 54

Authors

S Yeh

H Miyamoto

H Shima

C Chang

Affiliations

Soon will be listed here.

Abstract

While all three coactivators ARA70, steroid receptor coactivator 1, and RAC3/ACTR can enhance androgen receptor (AR) transcriptional activity at 1 nM dihydrotestosterone, we here demonstrate that only ARA70 can induce AR transcriptional activity >30-fold in the presence of 10 nM 17beta-estradiol (E2), but not diethylstilbestrol. The significance of this newly described E2-induced AR transcriptional activity in DU145 human prostate cancer cells was further strengthened by finding patients with Reifenstein partial-androgen-insensitive syndrome that fail in the E2-AR-ARA70 pathway. Together, our data suggest, for the first time, testosterone/dihydrotestosterone may not be the only ligands for the AR. E2 represents another important natural ligand for AR that may play an essential role for the AR function and the development of the male reproductive system.

Citing Articles

The emerging role of nuclear receptor coactivator 4 in health and disease: a novel bridge between iron metabolism and immunity.

Le Y, Liu Q, Yang Y, Wu J Cell Death Discov. 2024; 10(1):312.

PMID: 38961066 PMC: 11222541. DOI: 10.1038/s41420-024-02075-3.

The multifaceted therapeutic value of targeting steroid receptor coactivator-1 in tumorigenesis.

Chen Q, Guo P, Hong Y, Mo P, Yu C Cell Biosci. 2024; 14(1):41.

PMID: 38553750 PMC: 10979636. DOI: 10.1186/s13578-024-01222-8.

Revisiting Androgen Receptor Signaling in Breast Cancer.

Dai C, Ellisen L Oncologist. 2023; 28(5):383-391.

PMID: 36972361 PMC: 10166165. DOI: 10.1093/oncolo/oyad049.

Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance.

Altschuler J, Stockert J, Kyprianou N Int J Mol Sci. 2021; 22(4).

PMID: 33672595 PMC: 7924036. DOI: 10.3390/ijms22042100.

Foetal oestrogens and autism.

Baron-Cohen S, Tsompanidis A, Auyeung B, Norgaard-Pedersen B, Hougaard D, Abdallah M Mol Psychiatry. 2019; 25(11):2970-2978.

PMID: 31358906 PMC: 7577840. DOI: 10.1038/s41380-019-0454-9.

References

Rajfer J, Coffey D . Sex steroid imprinting of the immature prostate. Long-term effects. Invest Urol. 1978; 16(3):186-90. View

Brzozowski A, Pike A, Dauter Z, Hubbard R, Bonn T, Engstrom O . Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997; 389(6652):753-8. DOI: 10.1038/39645. View

Metzger D, White J, Chambon P . The human oestrogen receptor functions in yeast. Nature. 1988; 334(6177):31-6. DOI: 10.1038/334031a0. View

Wilding G, Chen M, Gelmann E . Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens. Prostate. 1989; 14(2):103-15. DOI: 10.1002/pros.2990140204. View

Bocquel M, Kumar V, Stricker C, Chambon P, Gronemeyer H . The contribution of the N- and C-terminal regions of steroid receptors to activation of transcription is both receptor and cell-specific. Nucleic Acids Res. 1989; 17(7):2581-95. PMC: 317644. DOI: 10.1093/nar/17.7.2581. View

Veldscholte J, Bolt-de Vries J, van Rooij H, Trapman J, Mulder E . Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: high affinity for progestagenic and estrogenic steroids. Biochim Biophys Acta. 1990; 1052(1):187-94. DOI: 10.1016/0167-4889(90)90075-o. View

Berry M, Metzger D, Chambon P . Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J. 1990; 9(9):2811-8. PMC: 551992. DOI: 10.1002/j.1460-2075.1990.tb07469.x. View

Tasset D, Tora L, Fromental C, Scheer E, Chambon P . Distinct classes of transcriptional activating domains function by different mechanisms. Cell. 1990; 62(6):1177-87. DOI: 10.1016/0092-8674(90)90394-t. View

Ofner P, Bosland M, Vena R . Differential effects of diethylstilbestrol and estradiol-17 beta in combination with testosterone on rat prostate lobes. Toxicol Appl Pharmacol. 1992; 112(2):300-9. DOI: 10.1016/0041-008x(92)90200-c. View

10.

Vogelzang N, Kennealey G . Recent developments in endocrine treatment of prostate cancer. Cancer. 1992; 70(4 Suppl):966-76. View

11.

Nagpal S, Saunders M, Kastner P, Durand B, Nakshatri H, Chambon P . Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors. Cell. 1992; 70(6):1007-19. DOI: 10.1016/0092-8674(92)90250-g. View

12.

Crawford E . Challenges in the management of prostate cancer. Br J Urol. 1992; 70 Suppl 1:33-8. DOI: 10.1111/j.1464-410x.1992.tb15865.x. View

13.

Pratt W, Welsh M . Chaperone functions of the heat shock proteins associated with steroid receptors. Semin Cell Biol. 1994; 5(2):83-93. DOI: 10.1006/scel.1994.1012. View

14.

Jacq X, Brou C, Lutz Y, Davidson I, Chambon P, Tora L . Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell. 1994; 79(1):107-17. DOI: 10.1016/0092-8674(94)90404-9. View

15.

Tsai M, OMalley B . Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994; 63:451-86. DOI: 10.1146/annurev.bi.63.070194.002315. View

16.

Taplin M, Bubley G, Shuster T, FRANTZ M, Spooner A, Ogata G . Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med. 1995; 332(21):1393-8. DOI: 10.1056/NEJM199505253322101. View

17.

Bissada N, Kaczmarek A . Complete remission of hormone refractory adenocarcinoma of the prostate in response to withdrawal of diethylstilbestrol. J Urol. 1995; 153(6):1944-5. View

18.

Bourguet W, Ruff M, Chambon P, Gronemeyer H, Moras D . Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha. Nature. 1995; 375(6530):377-82. DOI: 10.1038/375377a0. View

19.

Cavailles V, Dauvois S, LHorset F, Lopez G, Hoare S, Kushner P . Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995; 14(15):3741-51. PMC: 394449. DOI: 10.1002/j.1460-2075.1995.tb00044.x. View

20.

Horlein A, Naar A, Heinzel T, Torchia J, Gloss B, Kurokawa R . Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995; 377(6548):397-404. DOI: 10.1038/377397a0. View