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  • The expression and localization of Cx


    The expression and localization of Cx43, Cx46 and Cx50 in the anterior pituitary vary with physiological activities and with various conditions associated with both natural and pathological changes in hormone secretion. Anterior pituitary Cx43 and Cx50 levels increase and exhibit a more widespread distribution during periods of high Prl secretion [69,78]. In contrast, Cx46 levels decrease during the periods of high Prl secretion in mink [78]. In male mink, anterior pituitary Cx43 and Cx50 levels increases whereas Cx46 levels decrease during the active period of the annual reproductive cycle which is characterized by high gonadotropin serum levels [78]. The anterior pituitary and gonadal hormone secretion is deregulated during spontaneous autoimmune orchitis (AIO) in mink [80,81]. The anterior pituitary Cx43 and Cx50 levels drop whereas Cx46 rise in AIO mink compared to normal mink [78]. The ob/ob leptin-deficient and the db/db leptin receptor-deficient male mice exhibit abnormal anterior pituitary hormone and testosterone levels [78,82]. These animals are obese and diabetic. In ob/ob mice, anterior pituitary Cx43 and Cx46 levels decrease but not Cx50 [78]. Only anterior pituitary Cx43 drops in db/db mice [78]. Taken together, these findings show that the expression and localization of Cx43, Cx50 and Cx46 in the anterior pituitary are responsive to the hormone milieu and because of that they could constitute targets for chemicals that cause endocrine toxicity or that mimic hormone activity.
    Folliculostellate Chidamide and gap junctions The FS cells express the S100 protein [83], particularly the β isoform [84] and the glial fibrillary acidic protein (GFAP) [84,85], neither of these proteins is expressed by the endocrine cells. The S100 protein induces Prl secretion [86]. As mentioned above, FS cells are the source of several cytokines and factors affecting anterior pituitary hormone secretion and angiogenesis. Reciprocally, hormones and other endogenous factors influence FS cell proliferation, morphology, activity and network organization [84,[87], [88], [89], [90], [91], [92], [93], [94], [95]]. For example, FS cells show signs of activation during lactation in rats [89] and FS cells are larger and their cytoplasmic processes are more extensive during the high (Fig. 1L) than during the low (Fig. 1M) Prl secretion periods in mink [84]. In surrounding endocrine cells, the FS cells extend delicate cytoplasmic processes that organize the anterior pituitary in incomplete follicles (Figs. 1L and M) [84,96,97]. The FS cell cytoplasmic processes contact other FS cell processes establishing a intrapituitary cellular network [18,84]). These contacts involve the adhering junction protein E-cadherin [22]. In addition, FS cells exhibit high gap junction-mediated connectivity with endocrine cells [68] and with other FS cells [20,98]. The FS cells express the gap junction proteins Cx43 (Fig. 1F) [77], Cx46 (Fig. 1H) [78] and Cx50 (Fig. 1J) [78]. FS cell gap junctions are responsive to hypothalamic factors and gonadal hormones [18,99], adrenal cortex hormones [70], and leptin [71,100]. Moreover, the number of gap junctions increases in FS cells during development in both male and female rats [101,102], and it fluctuates during the estrous cycle and lactation period in female rats [18] and during the seasonal reproductive cycle in horses [73]. FS cell gap junctions are involved in the regulation of estradiol’s mitogenic activity in lactotropes [103]. These gap junctions participate in the transforming growth factor-β3 (TGF-β3)-induced secretion by the FS cells of basic fibroblast growth factor (bFGF), which modulates lactotrope proliferation [72]. The FS cells account for only 5–10% of the anterior pituitary cell population. Therefore, the establishment of FS cell lines greatly facilitated the study of FS cell physiology. In particular, the TtT/GF cell line [104] is widely used. TtT/GF cells express Cx43, Cx46 and Cx50 and they are joined by gap junctions [78,105]. Fig. 1G, I and K show the distribution of these connexins in cultured, resting TtT/GF cells. Cx43 localizes to the cell membrane and to a perinuclear region that is neither the Golgi apparatus nor lysosomes (Fig. 1G) [105]. Cx43 also localizes to the cell nucleus in TtT/GF cells [78]. Cx46 immunolabelling is mostly perinuclear (Fig. 1H) where it localizes to lysosomes [78]. In addition, Cx46 is present in the cell nucleus (Fig. 1I’) where it colocalizes with the nucleole marker Nopp140 [78]. Cx50 labelling occurs at the cell membrane while exhibiting a punctate pattern in the cytoplasm in TtT/GF cells (Fig. 1K) [78]. By contrast, Cx50 does not exhibit a nuclear localization.