Development steroid receptors

During development, steroid-hormone receptors become evident in target neurons of the brain 854... 

Zinc-fingers are common in DNA-binding proteins of eukaryotes but are not found in prokaryotes. Examples of zinc-finger proteins include the RNA polymerase III transcription factor TFIIIA, steroid receptors, and some gene products that control development. The zinc-finger consists of pairs of cysteine and/or histidine residues within an a-helix. These residues bind tightly to a Zn2+ ion, which allows the a-helical amino acids to interact with specific sequences. See Figure 12-18. 

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. 

Nestorone (12) is a member of the group of 19-nor-pregnane derivatives. It was developed by the Population Council and is one of the most potent progestins. Its profile at other steroid receptors is quite neutral. However, nesterone is not orally active, thus its use is limited to transdermal applications or implant devices. 

The 26-hydroxyl group is further oxidized to ecdysonoic acid (119) and 20-hy-droxyecdysonoic acid (120) [205] which have been identified in developing eggs of the desert locust, S. gregaria (Fig. 23). The occurrence of both compounds in Spodoptera littoralis pupae was also established. These oxidations are apparently inactivation steps. 26-Hydroxylation, 3-epimerization, 3-acetylation, and conjugation diminish the interaction with the steroid receptor and thus cem be viewed as inactivation. 

There is no doubt that patients who are both ERP+/PRP+ have a higher response to endocrine therapy at relapse. There are a substantial number of patients having either one or the other positive receptor status who also respond to hormonal therapy. It has been stated that ERP+ lesions are most likely to spread to bone, whereas those that are ERP- are more likely to develop visceral metastases, especially in liver or brain (Kl). Most breast cancers exhibit significant steroid receptor heterogeneity at a cellular level in both positive and negative cells, but in negative cells can be shown to be highly proliferative (Bl). 

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