AWL highlight gap maker

File produced at level 2

In healthy premenopausal women, 17-estradiol (E2), the main circulating estrogen, is produced by the ovaries after aromatization of androstenedione to estrone (E1) and subsequent conversion of E1 to E2. Among women with normal menstrual cycles, E2 functions as a circulating hormone that acts on distant target tissues (Figure 1A). In postmenopausal women, however, when the ovaries fail to produce E2 and in men who have naturally low levels of circulating E2%97E2 does not function as a circulating hormone; rather, it is synthesized in extragonadal sites such as breast, brain, muscle, bone, and adipose tissue where it acts locally as a paracrine or intracrine factor (8). Therefore, among both postmenopausal women and men, the determinant of E2 action is not circulating estrogens; rather, E2 function depends on estrogen biosynthesis from a circulating source of androgens (Figure 1B). Consequently, in these individuals, a major driver of E2 action is the aromatization of androgens to estrogens (8). Thus, tissue metabolism or inactivation of E2 is also an essential parameter controlling cellular estrogenic action (9). Tissue estrogen sulfotransferase (EST) is a critical
mediator of estrogen action (Figure 1, A and B). EST is a cytosolic enzyme that provides a molecular switch in target cells that inhibits estrogen activity by conjugating a sulfonate group to estrogens, thereby preventing binding to estrogen receptors and enhancing urinary excretion of the hormone. In this classic signaling pathway, ligand-activated ER dissociates from its chaperone heat-shock protein and binds as a dimer either directly to an estrogen response element (ERE) in target gene promoters or indirectly to activator protein 1 or specificity protein 1 response elements through protein tethering to DNA. After binding, these ER dimers interact with cofactors (coactivators or co suppressors) to regulate gene expression. Importantly, ERs acting on different response elements exert varying activity profiles. For example, when tethered via activator protein 1 sites, ER&%23945; exhibits E2-dependent transcription activation, whereas E2 bound to ER&%23946; has no effect on transcription. In addition, depending on the identity and concentration of the ligand, ER&%23945;-ER&%23945; homodimers, ER&%23946;-ER&%23946; homodimers, or ER&%23945;-ER&%23946; heterodimers are formed, with ER&%23945; playing a dominant role in heterodimer formation. There is overlap in binding sites for E2-liganded ER&%23945; and ER&%23946; when these receptors are present alone in cells. However, when both ERs are present, few sites are shared between ER&%23945; and ER&%23946;.

I got from some resource related my study now. I am using the estrogen receptor signaling to detect the role of estrogen in some pathway in zebrafish. I measure with the established method in the laboratory. I have an example on the above related as gap maker. Could you tell me what does it mean with bold condition?

I will explain you later? Hoping you could find the answer.


Other site related to separate between the special word related our field is like the below. The blue color indicates that it used for common word in my field, and yellow and red color is for limited to understand like technical word. So it is very difficult to understand for other persons. But we should change to other words so the people can understand what we mean.

Nice for your weekend.