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Transforming Growth Factor-ß3 Increases Gap-Junctional Communication among Folliculostellate Cells to Release Basic Fibroblast Growth Factor

Endocrinology Program and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901

Address all correspondence and requests for reprints to: Dipak K. Sarkar, Endocrinology Program and Department of Animal Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, New Jersey 08901. E-mail: sarkar{at}aesop.rutgers.edu.

	Abstract

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Folliculostellate (FS) cells are known to communicate with each other and with endocrine cells via gap junctions in the anterior pituitary. We investigated whether TGFß3 and estradiol, known to regulate FS cell production and secretion of basic fibroblast growth factor (bFGF), increases gap junctional communication to alter bFGF secretion from FS cells. FS cells in monolayer cultures were treated with TGFß3 or vehicle alone for 24 h and then microinjected with Lucifer Yellow and high-molecular-weight Texas Red dextran. Ten minutes later the transfer of dye among adjacent cells was recorded with a digital microscope. TGFß3 increased the transfer of dye. The TGFß3-neutralizing antibody and the gap junction inhibitor octanol reduced the effect of TGFß3 on the transfer of dye. The TGFß3-induced transfer of dye was unaltered by simultaneous treatment with estradiol. The steroid alone also had no effect. TGFß3 increased total and phosphorylated levels of connexin 43. Estradiol treatment did not produce any significant changes on basal or TGFß3-induced increases in connexin 43 levels. The gap-junction inhibitor octanol reduced TGFß3-increased levels of bFGF in FS cells. Taken together, these results suggest that TGFß3 may act on FS cells to increase gap-junctional communication to maximize its effect on bFGF secretion.

	Introduction

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FOLLICULOSTELLATE (FS) CELLS of the anterior pituitary are S-100-positive cells thought to be important for the regulation of pituitary endocrine cell functions (1, 2). FS cells have long and complex processes that interact with each other forming a mesh around endocrine cells (1). They also secrete factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and IL-6 (3). Recently it has been suggested that gap-junctional communication may be important for the function of FS cells (4, 5).

Gap junctions are composed of transmembrane channels joining the interiors of adjacent cells (6, 7, 8, 9, 10, 11). These junctions allow cell-to-cell exchange of cytoplasmic molecules like ions and small polar molecules including water, amino acids, calcium, inositol 1,4,5,-triphosphate (IP3), cAMP, sugars, and small peptides of 1000–1200 Da (12, 13, 14, 15, 16, 17). A large body of evidence suggests that gap junctions are involved in controlling growth and differentiation by allowing cell-to-cell transfer of signal molecules and metabolites (18, 19, 20). The exchange through gap junctions between the neighboring cells is dependent on the functional state of the channels, which can be estimated by measuring either the electrical coupling (e.g. current transfer or gap-junctional conductance) (21) or the dye coupling (e.g. transfer of a fluorescent probe from an injected cell to its neighboring cells) (22). The effects of TGFß3 on gap-junctional communication in the pituitary cells have not been studied. However, TGFß1 and forskolin modulate gap-junctional communication of Schwann cells, close cellular phenotypes of FS cells because both cell types produce the immunoreactive S-100 protein (23).

The TGFß family of peptides has been shown to be involved in the regulation of proliferation and secretion of various pituitary cells including lactotropes (24, 25). TGFß3 in particular, secreted by lactotropes, has been shown to increase the function of FS cells (2). FS cells, in turn, secreted bFGF and caused the proliferation of lactotropes (2). This interaction among FS cells and lactotropes seems to have relevance to prolactinomas, tumors of the prolactin-secreting lactotropes in the pituitary gland, especially in an estrogen-rich environment (24). Recent studies have identified the regulatory role of TGFß-related peptides in estradiol’s action on lactotropes (24, 25). Moreover, it was shown that TGFß3 and bFGF interact to facilitate the communication among lactotropes and FS cells, which is necessary for the mitogenic action of estradiol (24).

Gap junctions connect the cytoplasmic domains of contacting cells to allow metabolic and ionic exchange between them (26). Gap junctions consist of channel proteins called connexins, a family of proteins that, upon phosphorylation, increase permeabilization of the cells to molecules, which are permeable through gap junctions (26). There are various types of connexins. Of these, connexin 43 (Cx43) is known to express in astrocytes and in the pituitary (4, 27, 28, 29). It was shown that Cx43 is present in the mink pituitary and that this protein’s level changes with the seasons of the year and during pregnancy (3, 4). It has been suggested that Cx43 is found in the FS cell based on its distribution pattern in the pituitary (4). However, the production of Cx43 and the effect of TGFß3 on this protein in the presence and absence of estradiol in rat FS cells have not been determined. Therefore, we tested whether, in either the presence or absence of estradiol, TGFß3 increases Cx43 expression and gap-junctional communication in FS cells. Here we report that TGFß3, but not estradiol, increased Cx43 activation and gap-junctional communication to increase the release of bFGF from FS cells.

	Materials and Methods

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Folliculostellate cell cultures
An FS cell line established from anterior pituitary cells from cyclic female Fischer-344 rats was used (30). The cell line was maintained in DMEM/F-12 media with heat-inactivated 10% fetal bovine serum. Before gap-junction study, 1 x 10⁶ cells/well were maintained for 2 d in DMEM/F-12 medium containing serum supplement (consisting of 100 µM human transferrin, 5 µM insulin, 1 µM putrescine, and 30 nM sodium selenite) in 6-well plastic dishes. All chemicals were purchased from Sigma-Aldrich (St. Louis, MO) unless noted otherwise.

Dye transfer study
FS cultures were treated with various concentrations of TGFß3 prepared in fresh DMEM/F12 medium containing serum supplement at the indicated doses or with vehicle (4 mM HCL and 0.1% BSA) for 24 h before microinjection of the dye. TGFß3 and the TGFß3 blocking antibody were obtained from R&D Systems, Inc. (Minneapolis, MN). The blocking antibody was used at a concentration of 10 µg/ml with or without 10 ng/ml of TGFß3 for a period of 24 h before microinjection. Antirabbit -globulin (ARGG; Calbiochem, San Diego, CA) was used at a concentration of 10 µg/ml. In some cultures octanol, known to block gap-junctional communication (31, 32), was used. The blocker was used at concentrations of 1 mM and added to the culture 30 min before microinjection of the dye.

Confluent cultures were microinjected with Lucifer Yellow and a high-molecular-weight dextran (molecular weight 10,000 or 70,000) coupled to Texas Red (Molecular Probes, Eugene, OR). Care was taken to inject the dye in only one cell. We used an Eppendorf Injectman N12 microinjection system and a vibration-isolated platform. The amount of dye transfer to other cells was recorded 10 min after injection. Phase contrast, fluorescein isothiocyanate channel, and Texas Red channel images were photographed separately with appropriate filters.

Dye transfer was recorded with a charge-coupled device camera coupled to a TE-2000 inverted phase-contrast microscope equipped with epi-fluorescence (Nikon, Tokyo, Japan). Phase and double-fluorescent digital images in the fluorescein isothiocyanate and Texas Red channels were merged using Photoshop (version 7; Adobe, San Jose, CA). The number of Lucifer Yellow-positive cells (green in the figures) was counted visually in the growth factor-treated and control cultures.

Immunostaining for Cx43
FS cells (10,000 cells/well) were grown on 8-chamber slide plates in serum-containing medium. After 2 d of plating, the medium was changed to serum-free, chemically defined medium. On the following day, cells were treated for 24 h with vehicle (control) or TGFß3 (10 ng/ml) in serum supplement media. Cultures were washed with 0.1 M PBS for 5 min, fixed with 4% formaldehyde for 15 min, and then washed in 0.05 M Tris-HCl buffer (pH 7.6). These cultures were blocked for 1 h with Tris-HCl buffer containing 10% horse serum, 0.2% Triton X-100, and 0.1% sodium azide. Cultures were treated overnight at 4 C with primary rabbit anti-Cx43 (1:1000; Zymed Laboratory Inc., San Francisco, CA) in the blocking buffer. They were washed in Tris-HCl buffer and then incubated for 1 h with goat biotinylated antirabbit IgG (H+L) secondary antibody (1:3000; Vector Laboratories Inc., Burlingame, CA) in the blocking buffer. Cell-containing chambers were washed with Tris-HCl, dried, and mounted using 4',6'-diamino-2-phenylindole-containing mounting medium (H-1200; Vector Laboratories).

Western blot for Cx43
FS cells (500,000/well) were grown in 6-well plates in serum-containing medium. After 2 d of plating, the medium was changed to serum-free medium. On the following day, cells were treated for 3 or 24 h with vehicle (control), TGFß3 (10 ng/ml), estradiol (10 nM), or octanol (1.0 mM) in media containing serum supplement. Cells were then lysed in sample gel loading buffer containing Tris-HCl (pH 6.8), 2% glycerol, 0.05% bromophenol blue, 10% glycerol, and 5% ß-mercaptoethanol (14.4 M) and heated at 95 C for 5–6 min. Each sample was resolved on SDS-PAGE and transferred to Immobilon-P polyvinyl difluoride membranes (Millipore, Bedford, MA). Membranes were incubated for 1 h with anti-Cx43 antibody or anti-actin antibody (BD Biosciences, Palo Alto, CA) at room temperature in 5% milk, 50 mM Tris-HCl (pH 7.5), 150 mM NaCl, and 0.1% Tween 20. Membranes were then washed, incubated for 1 h with peroxidase-conjugated antimouse antibody, and developed using enhanced chemiluminescence reagent (Amersham, Piscataway, NJ). For quantification of Cx43 levels, the band intensities of Cx43 or phosphorylated Cx43 were determined using Scion Image software (Scion Corp., Frederick, MD) and normalized to the corresponding actin band intensities.

bFGF assay
FS cells (500,000/well) were grown in 6-well plates in serum-containing medium. After 2 d of plating, the medium was changed to serum-free medium. On the following day, cells were treated for 3 h with vehicle (control), TGFß3 (10 ng/ml), estradiol (10 nM), or octanol (1.0 mM) in medium containing serum supplement media. Cell supernatants were collected and assessed for bFGF levels using Quantikine immunoassay kits (R&D Systems). Cells were lysed in 100 µl of lysis buffer containing 150 mM Tris-HCl (pH 7.5), 300 mM NaCl, 0.1% Triton X-100, and a protease inhibitor cocktail (Sigma). Total protein concentration in each cell lysate was determined using the Bio-Rad assay to normalize the bFGF release per milligram of total protein.

Statistical analysis
The data shown in the figures and the text are means ± SEM. Comparisons between two groups were made using t tests. Data comparisons among multiple groups were done using one-way ANOVA. Post hoc tests involved the Student-Newmann-Keuls test. A value of P < 0.05 was considered significant.

	Results

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Effect of TGF ß3 and estradiol on FS cell gap-junctional communication
To determine whether TGFß3 modulates gap-junctional communication, FS cells were treated for 24 h with or without various doses of TGFß3. Afterward, cells were microinjected with the low-molecular-weight, gap-junction passing, fluorescent probe Lucifer Yellow, and the high-molecular-weight, gap-junction nonpassing, dextran coupled to a fluorescent probe, Texas Red (10 kDa). Figure 1 shows the dose-related effect of TGFß3. After 10 min of microinjection in control cultures treated with vehicle alone, Lucifer Yellow spread to 24.5 ± 3.5 cells (n = 46). After TGFß3 treatment with 5 ng/ml for 24 h, low-molecular-weight dye, but not the high-molecular-weight dextran-coupled fluorescent probe, spread was seen in approximately 2-fold more neighboring cells. This value was significantly higher (P < 0.01) than the number in the control group. Treatment with 10 ng/ml TGFß3 showed Lucifer Yellow dye spread in approximately 6-fold more (P < 0.001) neighboring cells. Compared with 5 ng/ml TGFß3, the 10 ng/ml TGFß3 treatment caused a significantly higher dye spread (P < 0.001), indicating a dose-dependent response to TGFß3 treatment. Interestingly, when cells were treated for 24 h with 10 ng/ml TGFß3 simultaneously with a TGFß3-neutralizing antibody (10 µg/ml), the Lucifer Yellow dye spread to neighboring cells was similar to the control values. In a preliminary study in which a small number of cultures (n = 3) were treated with the neutralizing antibody alone, dye transfer was seen in the number of cells (22 ± 7) similar to those in the control group (Fig. 1), suggesting that the antibody by itself had no effect on dye transfer. When cells were treated with TGFß3 and the nonspecific immunoglobulin ARGG, dye transfer occurred in the same number of cells as in the group treated with growth factor alone, suggesting that the increase in dye transfer was specifically due to TGFß3 and not due to the nonspecific presence of protein or antibodies.

View larger version (103K): [in this window] [in a new window]   FIG. 1. Effect of TGFß3 on dye transfer in FS cells. Confluent cultures of FS cells were treated for 24 h with either vehicle (CONT; A and B), 5 ng/ml TGFß3 (C and D), 10 ng/ml TGFß3 (E and F), 10 µg TGFß3 neutralizing antibody (A-TGFß3) with 10 ng/ml of TGFß3 (G and H), or 10 µg ARGG with 10 ng/ml of TGFß3 (I and J). One cell in each culture was microinjected with Lucifer Yellow and 10 kDa Texas Red dextran. Representative phase-contrast (A, C, E, G, and I) and phase overlaid with double-channel fluorescence (B, D, F, H, and J) images taken 10 min after dye injection are shown: Lucifer Yellow in green and Texas Red dextran in red. Overlapping regions appear as dark yellow. Scale bar, 10 µM. The number of Lucifer Yellow-positive cells counted 10 min after injection was used as the measure of dye transfer. Mean ± SEM values of Lucifer Yellow-positive cells are shown in the histogram (K); n = 9–46. *, P < 0.001, significantly different from the CONT-treated group; **, P < 0.001, significantly different from the CONT and the 5 ng/ml TGFß3-treated groups; ***, P < 0.001, significantly different from the 10 ng/ml of TGFß3-treated groups.

View larger version (81K): [in this window] [in a new window]   FIG. 2. Influence of octanol on TGFß3-induced dye transfer in FS cells. Representative phase-contrast (A, C, and E) and phase overlaid with double-channel fluorescence (B, D, and F) images of cultures treated with 1 mM octanol (OCT; A and B), 10 ng/ml TGFß3 (C and D), or 10 ng/ml TGFß3 with 1 mM octanol (TGFß3 + OCT; E and F) are shown: Lucifer Yellow is shown in green and Texas Red dextran in red. Scale bar, 10 µM. Mean ± SEM values of Lucifer Yellow-positive cells are shown in the histogram (G); n = 9–12. *, P < 0.001, significantly different from the TGFß3 + OCT-treated group.

View larger version (79K): [in this window] [in a new window]   FIG. 3. Influence of estradiol on TGFß3-induced dye transfer in FS cells. Representative images of phase-contrast (A, C, and E) and phase overlaid with double-channel fluorescence (B, D, and F) cultures treated with 10 nM estradiol-17ß (E2; A and B), 10 ng/ml TGFß3 (TGFß3; C and D), or 10 nM E2 with 10 ng/ml TGFß3 (TGFß3 + E2; E and F) are shown: Lucifer Yellow in green and Texas Red dextran in red. Scale bar, 10 µM. Mean ± SEM values of Lucifer Yellow-positive cells are shown in the histogram (G); n = 9–12.

Fluorescence microscopy studies of Cx43 immunoreactivity in FS cell cultures, using a commercially available specific antibody for Cx43, identified many FS cells stained with Cx43 (Fig. 4). The number of Cx43-positive cells was significantly increased (P < 0.01) after 10 ng/ml TGFß3 treatment. Visual comparisons of the cultures treated with TGFß3 and with control suggest that the intensity of the Cx43 staining per cells was increased by TGFß3 (Fig. 4). Estradiol-17 ß (10 nM) treatment failed to significantly affect the number of Cx43 immunoreactive FS cells (data not shown).

View larger version (36K): [in this window] [in a new window]   FIG. 4. Effects of TGFß3 on Cx43 immunoreactivity in FS cells. Representative microphotographs showing Cx43 immunoreactivity in FS cells treated for a period of 24 h with vehicle (A) or TGFß3 (10 ng/ml; B). Arrows identify some of the Cx43 immunopositive cells. –, 10 µm. C, Means ± SEM values of the percentage of the total cells that were Cx43 immunoreactive are shown; n = 3. *, P < 0.05, compared with control (CONT).

View larger version (27K): [in this window] [in a new window]   FIG. 5. Effects of TGFß3 and estradiol on phosphorylation and total Cx43 levels in FS cells. FS cells were treated for 24 h with TGFß3 (10 ng/ml) and estradiol(E2; 10 nM) alone or in combination. The levels of Cx43 were determined using an anti-Cx43 antibody. The antibody detects nonphosphorylated and phosphorylated forms of Cx43; a high-molecular-size band represents phosphorylated Cx43 (p-Cx43) and lower-size band represents nonphosphorylated Cx43. Total protein includes both the bands. A, Representative Western blot. B, Densitometric analysis showing changes in levels of p-Cx43 and non-p-Cx43 levels. C, Densitometric analysis showing changes in levels of total Cx43. Each bar represents mean ± SEM of three to five individual experiments. *, P < 0.05, compared with the respective control group.

View larger version (27K): [in this window] [in a new window]   FIG. 6. Role of gap-junctional communication in TGFß3-induced bFGF release from FS cells. The effects of TGFß3 (10 ng/ml) treatment for a period of 3 h was determined on phosphorylated (p-Cx43) or nonphosphorylated Cx43 proteins levels (A and B) and bFGF release in the presence and absence of octanol (OCT; C) from FS cells. A, Representative Western blots showing the effect of TGFß3 on p-Cx43, non-p-Cx43, and total Cx43 levels. B, Densitometric analysis showing changes in p-Cx43, non-p-Cx43, and total Cx43 levels after TGFß3 treatment. Each bar represents mean ± SEM of four individual experiments. *, P < 0.05, compared with respective control (CONT) groups. C, Effect of octanol on TGFß3-induced increase on bFGF release from FS cells. The level of bFGF in the culture media was assessed using immunoassay. Each bar represents mean ± SEM of four individual experiments. *, P < 0.05, compared with the respective control group.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

In the rat pituitary, formation of gap junctions between FS cells has been demonstrated using electron microscopy methods (38, 39). It has also been shown that FS cells communicate with other FS cells and endocrine cells, including prolactin-secreting lactotropes (5). Data obtained from our present study are in agreement with the observation that FS cells have functional gap junctions among them. One of the structural proteins of a gap junction, Cx43, has also been shown to express between FS cells in the mink anterior pituitary (4, 37). Detection of gap-junctional protein Cx43 in FS cells and the evidence of dye transfer between FS cells suggest that gap-junctional communication exists among FS cells.

The gap-junctional number in the anterior pituitary varied during the estrous cycle; it was highest in proestrous and estrous and increased during middle to late pregnancy in rats (38). This suggests that the gonadal factors such as estradiol may regulate the rate of occurrence of gap-junction in the anterior pituitary gland. Our data, which show no changes in dye transfer or Cx43 after estradiol, indicate that the steroid had no direct effect on the rate of occurrence and molecular transfer across gap junctions in the FS cells. The difference between these two observations could be explained by the fact that progesterone, which is elevated during the proestrous and estrous phases and during pregnancy, enhances the rate of gap junction formation between FS cells in the pituitary (39). Also, estradiol has been shown to increase production of TGFß3 from the lactotropes in the pituitary (2), and TGFß3 increases Cx43 levels and dye transfer in FS cells. Hence, estradiol’s gap-junctional communication-enhancing action in the in situ pituitary might be indirectly via increasing TGFß3 production from the lactotropes.

In the mink anterior pituitary, expression of Cx43 in FS cells was elevated during the spring and during lactation when the lactotrope cell number and prolactin secretion rate were very high (4). During these reproductive phases, enhanced expression of Cx43 in FS cells could have resulted from elevated TGFß3 production and secretion due to increased lactotropic cell number. In this study we found that, in FS cells, TGFß3 increased dye transfer, Cx43 phosphorylation and bFGF release, and all of these actions were suppressed by the gap-junctional blocker octanol. Together these data support a physiological role for TGFß3 in increasing gap-junctional communication to maximize its effect on FS cells.

Within the anterior pituitary, FS cells are known to form a cell network, which is involved in the propagation of cytosolic calcium waves via gap junctions after electrical stimulation (40). Furthermore, in the rat pituitary, these cells are believed to be involved in synchronization of intrapituitary electrical and calcium signaling (1, 41). Injection of IP3 into FS cells has been shown to initiate intercellular calcium waves that can be blocked by gap-junctional channel blockers (40). In this context, it is interesting to note that TGFß alters calcium influx in fibroblasts (42) and that TGFß-induced calcium influx involves the IP3 receptor (43). It could be hypothesized that the observed TGFß3-increased gap-junctional communication in FS cells plays a role in the coordination of the propagation of cytosolic calcium waves between these cells. However, this role of TGFß-related peptides needs to be experimentally verified by determining the effect of the growth factor on cytosolic calcium waves between the cells.

Because FS cells were shown to be activated by the TGFß3 secreted by the lactotropes (2), increased gap-junctional communication after TGFß3, which is reported in this paper, may also underlie the modulatory role of FS cells in pituitary function and pathology. For instance, increased gap-junctional communication could lead to more FS cells being activated by lactotropes that could then lead to more bFGF release by the FS cells that, in turn, could increase more lactotropic cell growth (Fig. 7). In conclusion, the finding of this paper may have relevance to TGFß3’s action on FS cells in terms of its physiological function, including bFGF release and calcium influx or pathological development, such as lactotropic cell tumors.

View larger version (20K): [in this window] [in a new window]   FIG. 7. A diagram summarizing the postulated role of gap-junctional communication between FS cells in estradiol-induced prolactinoma. Estradiol exposure elevates TGFß3 secretion from lactotropic cells that increases bFGF production from FS cells by activating TGFß receptor signaling and by increasing gap-junctional communication between FS cells. The increased release of bFGF induces lactotropic cell growth and tumors.

	Footnotes

 
This work was supported by National Institutes of Health Grants CA775500 and AA11591.

First Published Online June 16, 2005

Abbreviations: ARGG, Antirabbit -globulin; bFGF, basic fibroblast growth factor; Cx43, connexin 43; FS, folliculostellate; IP3, inositol 1,4,5,-triphosphate.

Received February 1, 2005.

Accepted for publication June 8, 2005.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Stojikovic S 2001 A novel view of the function of pituitary folliculo-stellate cell network. Trends Endocrinol Metab 12:378–380[CrossRef][Medline]
2. Hentges S, Boyadjieva N, Sarkar DK 2000 Transforming growth factor-ß3 stimulates lactotrope cell growth by increasing basic fibroblast growth factor from folliculo-stellate cells. Endocrinology 141:859–867[Abstract/Free Full Text]
3. Carding J, Carbajal ME, Vitale ML 2000 Biochemical and morphological diversity among folliculo-stellate cells of the mink (Mustela vison) anterior pituitary. Gen Comp Endocrinol 120:75–87[CrossRef][Medline]
4. Vitale ML, Cardin J, Gilula NB, Carbajal ME, Pelletier RM 2001 Dynamics of connexin 43 levels and distribution in the mink (Mustela vison) anterior pituitary are associated with seasonal changes in anterior pituitary prolactin content. Biol Reprod 64:625–633[Abstract/Free Full Text]
5. Morand I, Fonlupt P, Guerrier A, Trouillas J, Calle A, Remy C, Rousset B, Munari-Silem Y 1996 Cell-to-cell communication in the anterior pituitary: evidence for gap junction-mediated exchanges between endocrine cells and folliculostellate cells. Endocrinology 137:3356–3367[Abstract]
6. Unwin PNT, Zampighi G 1980 Structure of junction between communicating cells. Nature (Lond) 283:545–549[CrossRef][Medline]
7. Revel JP, Nicholson BJ, Yancey SB 1985 Chemistry of gap junctions. Annu Rev Physiol 47:263–279[CrossRef][Medline]
8. Loewenstein WR 1981 Junctional intracellular communication: the cell to cell membrane channel. Physiol Rev 61:829–913[Free Full Text]
9. Gilula NB 1984 The biosynthesis of gap junctions. Fed Proc 43:2678–2680[Medline]
10. Warner A 1988 The gap junction. J Cell Sci 89:1–7[Free Full Text]
11. Stagg RB, Fletcher WH 1990 The hormone-induced regulation of contact-dependent cell-cell communication by phosphorylation. Endocr Rev 11:302–325[Abstract]
12. Simpson I, Ross B, Loewenstein WR 1977 Size limit of molecules permeating the junctional membrane channels. Science 195:294–296[Abstract/Free Full Text]
13. Flagg-Newton JL, Simpson I, Loewenstein WR 1979 Permeability of the cell to cell membrane channels in mammalian cell junction. Science 205:404–407[Abstract/Free Full Text]
14. Schwartzmann G, Wiegandt H, Rose B, Zimmerman A, Ben-Haim D, Loewenstein WR 1981 Diameter of the cell to cell junctional membrane channels as probed with neutral molecules. Science 213:551–553[Abstract/Free Full Text]
15. Saez JC, Connor JA, Spray DC, Bennett MVL 1989 Hepatocyte gap junctions are permeable to the second messenger, inositol 1, 4, 5' triphosphate and to calcium ions. Proc Natl Acad Sci USA 86:2708–2712[Abstract/Free Full Text]
16. Charles AC, Naus CCG, Zhu D, Kidder GM, Dirksen ER, Sanderson MJ 1992 Intercellular calcium signaling via gap junction in glioma cells. J Cell Biol 118:195–201[Abstract/Free Full Text]
17. Murray SA, Fletcher WH 1984 Hormone-induced intracellular signal transfer dissociates cyclic AMP-dependent protein kinase. J Cell Biol 98:1710–1719[Abstract/Free Full Text]
18. Warner AE, Guthrie SC, Gilula NB 1984 Antibodies to gap junction protein selectively disrupt junctional communication in the early amphibian embryo. Nature (Lond) 311:127–131[CrossRef][Medline]
19. Loewenstein WR 1979 Junctional intracellular communication and the control of growth. Biochim Biophys Acta 560:1–65[Medline]
20. Mehta PP, Bertram JS, Loewenstein WR 1986 Growth inhibition of transformed cells correlates with their junctional communication with normal cells. Cell 44:187–196[CrossRef][Medline]
21. Neyton J, Trautmann A 1986 Physiological modulation of gap junction permeability. J Exp Biol 124:93–114[Abstract/Free Full Text]
22. Stewart WW 1978 Functional connection between cells revealed by dye-coupling with a highly fluorescent naphtalimide tracer. Cell 14:741–759[CrossRef][Medline]
23. Ishikawa H, Nogami H, Nobuyuki S 1983 Novel clonal strain from adult rat anterior pituitary producing S-100 protein. Nature (Lond) 303:711–713[CrossRef][Medline]
24. Hentges S, Sarkar DK 2001 Transforming growth factor-ß regulation of estradiol-induced prolactinomas. Front Neuroendocrinol 22:340–363[CrossRef][Medline]
25. Sarkar DK, Hentges ST, De A 1998 Hormonal control of pituitary prolactin-secreting tumors. Front Biosci 3:d934–d943
26. Bennett MV, Barrio LC, Bargiello TA, Spray DC, Hertzberg E, Saez JC 1991 Gap junctions: new tools, new answers, new questions. Neuron 6:305–320[CrossRef][Medline]
27. Chen KC, Nicholson C 2000 Spatial buffering of potassium ions in brain extracellular space. Biophys J 78:2776–2797[Abstract/Free Full Text]
28. Yeager M, Unger VM, Falk MM 1998 Synthesis, assembly and structure of gap junction intercellular channels. Curr Opin Struct Biol 8:517–524[CrossRef][Medline]
29. Evans WH, Martin PE 2002 Gap junctions: structure and function. Mol Membr Biol 19:121–136[CrossRef][Medline]
30. Pastorcic M, De A, Boyadjieva N, Vale W, Sarkar DK 1995 Reduction in the expression and action of transforming growth factor ß1 on lactotropes during estrogen-induced tumorigenesis. Cancer Res 55:4892–4898[Abstract/Free Full Text]
31. Vazquez-Martinez R, Shorte SL, Boockfor FR, Frawley LS 2001 Synchronized exocytotic bursts from gonadotropin-releasing hormone-expressing cells: dual control by intrinsic cellular pulsatility and gap-junctional communication. Endocrinology 142:2095–2101[Abstract/Free Full Text]
32. Veenstra RD, DeHaan R 1986 Measurement of single channel currents from cardiac gap junctions. Science 29:972–974
33. Chaturvedi K, Sarkar D 2004 Involvement of PKC dependent p44/42 MAP kinase signaling pathway for cross-talk between estradiol and TGFß3 in increasing bFGF in folliculostellate cells. Endocrinology 145:706–715[Abstract/Free Full Text]
34. Yeager M, Nicholson BJ 1996 Structure of gap junction intercellular channels. Curr Opin Struct Biol 6:183–192[CrossRef][Medline]
35. Hansson E, Muyderman H, Leonova J, Allansson L, Sinclair J, Blomstrand F, Thorlin T, Nilsson M, Ronnback L 2000 Astroglia and glutamate in physiology and pathology: aspects on glutamate transport, glutamate-induced cell swelling and gap-junction communication. Neurochem Int 37:317–329[CrossRef][Medline]
36. Medda P, Pepper MS, Traub O, Willecke K, Gros D, Beyer E, Nicholson B, Paul D, Oreil L 1993 Differential expression of gap junction connexins in endocrine and exocrine glands. Endocrinology 133:2371–2378[Abstract]
37. Yamamoto T, Hossain MZ, Hertzberg EL, Uemura H, Murphy LJ, Nagy JL 1993 Connexin 43 in rat pituitary: localization at pituicyte and stellate cell gap junctions and within gonadotrophs. Histochemistry 100:53–64[CrossRef][Medline]
38. Soji T, Mabuchi Y, Kurono C, Herbert DC 1997 Folliculo-stellate cells and intercellular communication within the rat anterior pituitary gland. Microsc Res Tech 39:138–149[CrossRef][Medline]
39. Sakuma E, Herbert DC, Soji T 2002 Leptin and ciliary neurotrophic factor enhance the formation of gap junctions between folliculo-stellate cells in castrated male rats. Arch Histol Cytol 65:269–278[CrossRef][Medline]
40. Fauquier T, Guerineau NC, McKinney RA, Bauer K, Mollard P 2001 Folliculostellate cell network: a route for long-distance communication in the anterior pituitary. Proc Natl Acad Sci USA 98:8891–8896[Abstract/Free Full Text]
41. Guerineau NC, Bonnefont X, Stoeckel L, Mollard P 1998 Synchronized spontaneous Ca2+ transients in acute anterior pituitary slices. J Biol Chem 273:10389–10395[Abstract/Free Full Text]
42. Muldoon LL, Rodland KD, Magun BE 1998 Transforming growth factor ß and epidermal growth factor alter calcium influx and phosphatidylinositol turnover in rat-1 fibroblasts. J Biol Chem 263:18834–18841
43. McGowan TA, Madesh M, Zhu Y, Wang L, Russo M, Deelman L, Henning R, Joseph S, Hajnoczky G, Sharma K 2002 TGFß-induced Ca (2+) influx involves the type III IP(3) receptor and regulates actin cytoskeleton. Am J Physiol Renal Physiol 282:F910–F920

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