Estrogen Analysis Using Mass Spectrometer

Estrogen Analysis Using Mass Spectrometer



Literature Review Estrogen Analysis utilising Mass Spectrometer

1. Background information on estrogen  

 Estrogen biosynthesis which happens in the breast tissue of postmenopausal women is basically distinct from that which happens in the ovaries of premenopausal women. Unlike the ovaries, breast tissue needs the proficiency to synthesize androgen precursors. [26] Hence, estrogen output is reliant upon the accessibility of circulating C-19 androgen antecendent and localized alteration to estrogens in goal tissues for example the breast.

The estrogens can then be issued into the circulation, which presents biomarkers of tissue estrogen biosynthesis. [6] Thyroxine, thyroids principle hormone, affects the activity of cells throughout the body. Increased levels of thyroxine in the blood stimulated cells to become more active. The activity of this gland is controlled by the hypothalamus and the anterior pituitary glands. When the hypothalamus senses that the thyroxine level in the blood is low, it secretes a hormone known as Thyroid releasing hormone (TRH), stimulating the anterior pituitary gland to secrete Thyroid stimulating hormone (TSH) and this stimulating the release of thyroxine from the thyroid gland. The feedback happens to keep thyroxine level constant. 17ß-Estradiol (estradiol) induces tumors in animal forms and in humans and increased estrogen grades in postmenopausal women are affiliated with expanded breast cancerous infection risk. This is considered to originate from a dual means in which estradiol can proceed either as a hormone to stimulate aberrant cell expansion or as the forerunner to the formation of genotoxic metabolites [3]. Estrogen receptors (ERa and ERß) are important transcriptional regulators that mediate a number of fundamental processes, including regulation of the reproductive system and maintenance of skeletal and cardiovascular tone. As such, these receptors are molecular targets of drugs used to treat diseases such as breast cancer and osteoporosis. Both positive and negative effects of ER ligands have been demonstrated in target tissues, so tissue-selective ER ligands have been developed and are called selective estrogen receptor modulators (SERMs).

Traditional medicine programs for ER modulators are most commonly associated with the use of receptor-binding as a primary screen to identify high affinity ligands, and then use an in vitro cell assays to determine the functional activity of the ligand (1). Compounds with the desired intrinsic properties for selective affinity and functional response are then evaluated in vivo efficacy in animal models of disease targets. Although the drug-discovery paradigm has been used successfully to identify the most clinically relevant SERMs discovered to date, the ability of in vitro biochemical and cellular functional assays to translate in vivo tissue selectivity is limited. cofactor recruitment assays were a useful tool for identifying ligand-induced conformational changes for many nuclear receptors, but may be less effective for the profiling of SERMs because key coactivator interaction surface (AF-2) was blocked ligand-induced repositioning of helix 12.

Classical approaches to the structural analysis of receptor-ligand interactions involve the use of X-ray crystallography and NMR spectroscopy. The importance of studying changes in the dynamics of proteins in the modulation of the ...