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    • The role of cell to cell

    2022-08-03

    The role of cell-to-cell interactions in coordinating the cells’ behaviour to ensure an appropriate anterior pituitary hormone response is receiving increasing attention. Anterior pituitary Sodium Danshensu interact with neighbouring cells through junctional complexes. As their name implies, the complexed are composed of different types of intercellular junctions namely: tight junctions, adhering junctions, desmosomes and gap junctions (Fig. 1A). Annular junctional complexes are extensive. The fact that they are frequently encountered in anterior pituitary cells is suggestive of a rapid turnover of the many different types of junctions (Fig. 1A and A’). The endocrine cells are joined to FS cells by different types of intercellular junctions (Fig. 1B). Tight junctions, adherens junctions, desmosomes (Fig. 1A, B and E) and gap junctions (Fig. 1B, C and D, and [14,15]) join neighbouring FS cells. Endoplasmic reticulum cisternae typically accompany the junctions (Fig. 1D). The presence of gap junctions among anterior pituitary cells indicates that they are highly communicating cells. Recycled gap junctions are found in annular junctions (Fig. 1C). FS cells and endocrine cells of the same lineage establish homotypic contacts among themselves that allow them to form individual cellular tridimensional networks within the pituitary parenchyma [16,17]. Recent investigations begin to identify not only the cell junctions involved in the organization of these networks but, in addition, their essential functional contribution to the network [[18], [19], [20], [21], [22], [23], [24]]. Moreover, hypothalamic and peripheral hormones and physiological stimuli influence Sodium Danshensu the network shape and activity [[25], [26], [27], [28], [29]]. In this manner, gap junctions involved in the establishing of the network are potential targets for environmental toxins with hormone-like activities.
    Toxicant effects on anterior pituitary function The fine tuning of anterior pituitary hormone secretion ensures optimal and appropriate responses of the gland to physiological needs and environmental challenges. Environmental pollutants and drugs that compromise this delicate hormonal equilibrium may result in various pathologies such as infertility, obesity and cancer [[30], [31], [32]]. This notwithstanding, the research focussed on the effect of toxicants and drugs on end-target organs like the gonads and the adrenal cortex. To date reports on the effect of metals and xenobiotics, particularly the “endocrine-disrupting chemicals” on the anterior pituitary are scarce. These studies show that toxicants affect anterior hormone levels in humans and rodents, the extent depending on factors like, age, sex, dose and time of exposure [24,[33], [34], [35], [36], [37], [38], [39], [40], [41]]. When interfering with anterior pituitary hormone secretion, toxicants may act directly on pituitary cells or they may have secondary and tertiary effects when interfering with hypothalamic factors and feedback mechanisms from target organs/tissues [33,39]. By mimicking a given hormonal activity, some toxicants and pharmaceuticals directly interfere with the growth, the proliferation and the reactivity of anterior pituitary cells, and thus modify hormone synthesis and secretion [[33], [34], [35], [36], [37]42,43]. Toxicants also affect autocrine, juxtacrine or paracrine mechanisms, cell-to-cell interactions and intercellular network organization in the rodent anterior pituitary [24,36]. Although these studies revealed adverse effects of these compounds on the pituitary none have addressed their potential impact on anterior pituitary gap junctions.
    Gap junctions, hemichannels and connexins Gap junctions are key players in the establishment of intercellular communication. Gap junction channels are formed by the association of proteins named connexins (Cx). To date around 20 different connexins isoforms have been described in rodents and human [44]. Six connexins oligomerize to form a connexon or hemichannel. Each connexon moves to the plasma membrane where it interacts with a connexon from a neighbouring cell to constitute a channel that communicates the cytoplasm of the cells involved in the gap junction [45]. The free movement of small molecules across the intercellular channels allows sharing of information among communicating cells. A network of gap junction-mediated communicating cells assures the integration and coordination of each individual cell’s response resulting in a synchronized and timely reaction of the connected cells. Connexons or hemichannels not engaged in gap junctions transmit information from the intracellular milieu to the extracellular space and vice versa. Substances released via hemichannels such as ATP, NAD+ and glutathione impact neighbouring cells in a paracrine manner [46]. In addition, connexin molecules or fragments interact with intracellular regulators and modulate cell activities independently of gap junction/hemichannel formation [44,[47], [48], [49]].