Nuclear androgen receptors

Moreover, DHT was shown to bind preferentially to specific nuclear (androgen) receptor proteins (Mainwaring, 1969 Fang et al.,... 

Fig. 7. Changes in the contents of specific mRNAs and nuclear receptors in mouse kidney after exposure to testosterone. Female NCS mice were given a single intraperitoneal dose of 10 mg of testosterone at time zero. Thereafter, nuclear androgen receptors were measured, The specific mRNAs of three proteins were also assayed, namely for ornithine decarboxylase (- -), KAP (-0-) and /3-glucuronidase (- -). Redrawn from Catterall et al. [26],...

Mechanism of Action. Flutamide being an orally active and potent competitive inhibitor of speeific nuclear androgen receptors in target tissues e.g., seminal vesicles, adrenal cortex and prostate. Its pharmacologieal aetion is mainly on aeeount of its major metabolite, 2-hydroxyflutamide, as given below ... 

Endocrine disruptors apparently affect all nuclear receptors. Thus, a notable increment in impotence, alterations of the libido and of oligospermia in workers exposed to pesticides has been described. These alterations are due to the action of some compounds with estrogen-mimetic action and to their interaction with the androgen receptor. Additionally, alterations of thyroid function have been detected in rats exposed to dioxin and other toxic agents,... 

PRMTl, a nuclear receptor coactivator, exists as in a 330 kDa complex and is a H4 Arg-3 methyltransferase [133,215]. The enzyme appears to be a chromatin bound, and evidence from immunodepletion and knockout studies suggest that it is the principle, if not sole, H4 Arg-3 methyltransferase [133,215]. Mutation of the S-adenosyl methionine binding site in PRMTl annihilated its nuclear receptor coactivator activity with the androgen receptor, providing evidence for the importance of the methylation event in gene expression [215]. Yeast Rmtl, which is homologous to human PRMTl, methylates Arg-3 only in free H4 [208]. 

Gene expression inhibition. Hexane extract of the fruit, taken orally by male adults at a dose of 320 mg/day, significantly reduced nuclear estrogen and androgen receptors in the prostate . 

Steroid hormones achieve their effects on target tissues through intracellular receptor proteins. According to recent views, oestrogen and progestin receptors are localized in the nuclear compartment of the cells, whereas glucocorticoid receptors may reside in both the cytoplasm and the nucleus. Determination of the intracellular localization of androgen receptors awaits the development of (monoclonal) antibodies which will enable immunohistochemical studies. The molecular aspects of the mechanism of action of steroid hormones will be covered in other chapters [1-3] in this volume. The present chapter deals with the characterization, assay and purification of steroid receptors. 

H19. Hsieh, T., and Wu, J. M., Induction of apoptosis and altered nuclear/cytoplasmic distribution of the androgen receptor and prostate-specific antigen by 1 alpha, 25 dihydroxyvitamin D3 in androgen responsive LNCaP cells. Biochem. Biophys. Res. Commun. 235, 539-544 (1997). 

ER Estrogen Receptor, AR Androgen Receptor, GR Glucocorticoid Receptor, TR Thyroid Receptor, RAR Retinoic Acid Receptor, RXR Retinoie X Receptor, PR Progesterone Receptor, VDR Vitamin D Receptor, PPAR Peroxisome Proliferator-Activated Receptor, PXR Pregnane X Receptor, ROR Retinoic Acid-Related Orphan Receptor, NHF-4 Hepatocyte Nuclear Eactor 4, ERR Estrogen-Related Receptor... 

The activation or inhibition of nuclear hormone receptors by synthetic androgens, with a readout (way) downstream of transcriptional regulation such as muscle growth or inhibition of sperm production (a highly educational example, isn t it). 

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