| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Department of Animal Sciences, Rutgers, State University of New Jersey (N.B., D.K.S.), New Brunswick, New Jersey 08901; and the Departments of Veterinary and Comparative Anatomy (S.H.), Pharmacology, and Physiology, Washington State University, Pullman, Washington 99164-6520
Address all correspondence and requests for reprints to: Dr. D. K. Sarkar, Department of Animal Sciences, Rutgers, State University of New Jersey, New Brunswick, New Jersey 08901.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The TGFß family of peptides includes three highly homologous isoforms in mammals that exert their actions via the type I and type II TGFß receptors. These isoforms of TGFß inhibit or stimulate the growth and/or gene transcription in many cell types, including epithelial, endothelial, lymphoid, myeloid, and mesenchymal cells (9, 10, 11). Despite the similarity in structure of each of the isoforms of TGFß, they each have distinct promoters and differential expression (reviewed in Ref. 12). There are also cell-specific differences in responsiveness to TGFß isoforms that may be attributable to receptor affinity and susceptibility to alterations by extracellular factors (13).
We previously demonstrated that estradiol-induced prolactinoma formation is associated with a significant reduction in the expression of both TGFß1 and the type II TGFß receptor (TßR-II) in pituitary lactotropes (5, 6, 7, 8, 14). TGFß1, a potent inhibitor of epithelial cell proliferation, is produced in and acts on lactotropes (5, 6, 7, 8). The reduction of the function of this inhibitory factor is one possible component of estrogen-induced mitogenesis. TßR-II is essential for TGFß to inhibit cell growth (14, 15, 16), so the reduction in this receptor, which follows estrogen treatment, is another way in which estrogen can cause a loss in cell growth inhibition.
In addition to the reduction in the growth inhibitory actions of
TGFß1, estrogen treatment results in the production, secretion, and
activation of several growth stimulatory factors in the anterior
pituitary. Some of these factors act on lactotropes and have been
localized to nonendocrine cells of the anterior pituitary, including
basic fibroblast growth factor (bFGF), insulin-like growth factor I,
and TGF
(17, 18, 19). Recently, we determined that there is an increase
in TGFß3 during estradiol-induced tumorigenesis, TGFß3 stimulates
lactotropic cell proliferation in the presence of estrogen, and
immunoneutralization of endogenous TGFß3 reduces estradiol’s growth
stimulatory action on lactotropes (8). The direct action of TGFß
isoforms is generally growth inhibitory on epithelial cells. However,
in some cell types, TGFß stimulates cell growth via a paracrine
mechanism by increasing growth stimulatory peptide growth factors (11).
Whether such a mechanism exists in pituitary cell culture was examined
in this study. We found that TGFß3 action is mediated via paracrine
interactions with the folliculo-stellate (FS) cells of the anterior
pituitary. In addition, we provide evidence that bFGF is a mediator of
TGFß3 action on lactotropic cell proliferation.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Primary cultures of anterior pituitary cells
Seven to 10 days postovariectomy and estradiol capsule
implantation, rats were killed, and the anterior pituitaries were
collected and enzymatically dissociated as described by us previously
(6). The cells were grown on poly-L-lysine-coated
coverslips and maintained in DMEM/Ham’s F-12 (1:1; Sigma,
St. Louis, MO; containing 100 U/ml penicillin and 100 µg/ml
streptomycin) with 10% FCS (HyClone Laboratories, Inc.,
Logan, UT) for 1 day, then in medium containing 2.5% FCS and 10%
horse serum for another 2 days. Cultures were then maintained in
serum-free DMEM/F-12 containing serum supplement (100 µM
human transferrin, 5 µM insulin, 1 µM
putrescine, and 30 nM sodium selinite) during
experimentation.
Enrichment of lactotropes
Lactotropes were enriched from dissociated anterior pituitary
cell suspensions using a discontinuous Percoll gradient. Cells were
dissociated as described above, filtered through a sterile 30-µm pore
size filter to remove any tissue fragments, then layered, using a 1-ml
plastic pipette, atop the Percoll (Sigma) gradient
consisting of 60%, 50%, and 35% Percoll layers (pH 7.3; osmolality,
300 mosmol) as described previously (20). The gradient was
centrifuged at 450 x g for 20 min. The cells at the
35%/50% interface were collected with a glass pipette and seeded on
poly-L-lysine-coated coverslips as enriched
lactotropes and treated as described above for primary cultures of
anterior pituitary cells. Cultures of mixed anterior pituitary cells
from the estradiol-treated F-344 rats contain approximately 69 ±
2% PRL-immunoreactive cells (7). Cultures enriched by Percoll gradient
separation contained 81 ± 3% (n = 4 separate cultures)
PRL-immunoreactive cells; these cultures were considered to be free of
FS cells, as no S-100 immunoreactivity was detected in cultures that
were Percoll separated. FS cells were identified as cells staining
positively for S-100, which was carried out using S-100 antibody
(1:400; Zymed Laboratories, Inc., San Francisco, CA).
Cultured cells were ethanol fixed. Nonspecific binding was blocked with
3% normal serum. Cells were incubated with primary antibody overnight
at 4 C. The primary antibody was detected with nitro blue tetrazolium
and 5-bromo-4-chloro-3-indolyl-phosphate (Zymed Laboratories, Inc.). Positive controls were cultures of mixed anterior
pituitary cell types where the presence of S-100 staining was detected.
Negative controls were carried out by incubating cells with primary
antibody that had been preabsorbed with a 100-fold excess of antigen
(Zymed Laboratories, Inc.) and staining with nitro blue
tetrazolium and 5-bromo-4-chloro-3-indolyl-phosphate; no S-100
immunoreactivity was detected when the antibody was preabsorbed.
Cell lines
The RC-4B/C cell line, a cell line containing cells with
phenotypes of each of the types of endocrine cells found in the
anterior pituitary gland, was obtained from American Type Culture Collection (Manassas, VA) and maintained according to the
supplier’s instructions. During experimentation, these cells were
maintained in DMEM containing serum supplement.
We established an FS cell line from a primary culture of anterior pituitary cells from cyclic female Fischer-344 rats. The dissociated cells were subjected to Percoll separation as described above, except that the cells from the 50%/60% interface were collected and plated onto a 100-mm culture dish. The culture was maintained in DMEM/F-12 containing 10% FCS until confluent, then the cells were distributed to multiple plates. After 10 passes, immunohistochemical procedures for S-100 detection (described above) revealed that the cultures contained only S-100-positive cells. S-100 has been demonstrated to be an effective marker of FS cell phenotype (21, 22, 23). The FS cell line was maintained in DMEM/F-12 with 10% FCS. During experimentation, FS cells were maintained in DMEM/F-12 with serum supplement. The FS cells used were between generations 20 and 30.
Treatments
Cultures were treated with DMEM containing serum supplement. The
estrogen used was 17ß-estradiol (Sigma; water-soluble)
at 10-nM concentrations. Recombinant human TGFß3 was
obtained from R&D Systems (Minneapolis, MN) and reconstituted in 0.1%
BSA and 4 mM HCl. The doses used were 0–10 ng/ml.
Recombinant human bFGF (R&D Systems) was dissolved in PBS containing
0.1% BSA and 1 mM DTT and used at concentrations of 0–10
ng/ml. Control cultures received vehicle. In all of the cell
proliferation experiments, the total treatment time was 96 h, with
the medium and treatment changed at 48-h intervals. For conditioned
medium experiments, FS cells were treated with TGFß3 for 48 h,
and conditioned media from these cultures were collected, centrifuged
to remove cell debris, and placed on cultures of enriched lactotropes.
Immunoneutralization studies were carried out in a similar fashion,
except that the medium samples collected from the treated FS cells were
incubated for 2 h with bFGF antibody (0–10 µg/ml; R&D Systems)
at room temperature before placement on lactotropic cell cultures.
Antirabbit 
-globulin (ARGG; 10 µg/ml; Calbiochem, San
Diego, CA) was used as an antibody control.
Cell proliferation assays
Lactotropic cell proliferation was determined by identifying
cells that display both bromodeoxyuridine (BrdUrd) and PRL
immunoreactivities, as described by us previously (24). BrdUrd is a
marker of DNA synthesis; therefore, double stained cells were
considered to be dividing lactotropes. Cultures were treated with 0.1
mM BrdUrd 4 h before fixation with 99% ethanol. Cells
were incubated at 4 C overnight with BrdUrd monoclonal mouse IgG
(1:200; Becton Dickinson and Co. Immunocytochemistry
Systems, San Jose, CA) and stained using the Vectastain
ABC kit (Vector Laboratories, Inc., Burlingame, CA) with
diaminobenzidine as the chromagen. The cells were then incubated with
PRL antibody (1:100,100 PRL-S9; NIDDK) at 4 C overnight and stained
using the Vectastain ABC-AP kit. Negative controls were
conducted by exposing cells to 3% normal serum from the host species
rather than primary antibody and also by preabsorbing the antibody with
a 100-fold excess of antigen. Two investigators independently performed
cell counts that involved counting 5 separate areas in each coverslip
with approximately 500 cells/area. For some experiments using purified
cell populations, only BrdUrd immunoreactivity was determined, and the
results are presented as the percentage of BrdUrd-incorporating cells
of the total cell population that was determined by nuclear staining
with Harris hematoxylin.
Some experimental data dealing with cell proliferation were verified using an alternate method to BrdUrd, which was the tritiated thymidine incorporation assay. The tritiated thymidine assay was carried out as we have previously described (7). In brief, cultures were treated with 2 µCi/well [3H]thymidine (SA, 82.2 C/mM; Amersham Pharmacia Biotech, Arlington Heights, IL) for 4 h. The cells were washed with fresh medium containing a 1000-fold excess of cold thymidine, dispersed in trypsin, centrifuged, and precipitated in 10% trichloroacetic acid. The precipitates were digested in 0.5 M NaOH and placed in 10 ml ACSII scintillation cocktail (Amersham Pharmacia Biotech) for counting the disintegrations per min with a scintillation counter. An additional method used for cell counting was a modified 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. This assay is an indicator of mitochondrial activity. The metabolism of MTT has been shown to correlate well with cell number (manufacturer’s specifications). This assay was obtained from Promega Corp. (Madison, WI) and was carried out in accordance with the manufacturer’s instructions.
Quantification of bFGF levels
The content of bFGF was determined in medium collected from FS
cells, enriched lactotropes, or mixed anterior pituitary cells treated
with vehicle, estradiol, or estradiol and TGFß3 using an
enzyme-linked immunosorbent assay (ELISA). A preliminary study was
conducted in which the different number of mixed anterior pituitary
cells and FS cells were cultured, and medium samples were obtained to
determine the medium concentrations of bFGF. It was observed that
approximately 200,000 FS cells and 1,200,000 mixed pituitary cells were
needed to obtain medium levels of bFGF in the good range of the
ELISA. We used 200,000 FS cells, 1,200,000 mixed pituitary cells, and
1,200,000 enriched lactotropes. The bFGF assay was carried out using
the bFGF Quantakine ELISA kit (R&D Systems). The assay was performed as
suggested by the manufacturer. According to the manufacturer’s
specifications, this kit displays no cross-reactivity with related
peptides; no cross-reactivity was observed with TGFß1–3. This assay
measures between 1–320 pg/ml bFGF in culture medium.
Statistical analysis
The data shown in the text and figures are the mean ±
SEM. Data were analyzed using one-way ANOVA or Student’s
t test when only two treatment groups were compared.
Post-hoc analyses after ANOVA employed the
Student-Newmann-Keuls test. P < 0.05 was considered
significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
). These data were verified using
tritiated thymidine assays (Fig. 1B). TGFß3 significantly increased
the incorporation of tritiated thymidine into cells at 0.01, 0.1, and
1.0 ng/ml in the presence of estradiol. TGFß3 had no effect on
tritiated thymidine incorporation in cultures of enriched lactotropes
up to the dose of 1.0 ng/ml, at which moderate inhibition of thymidine
incorporation occurred. The data demonstrate that a differential
response to TGFß3, in terms of lactotropic proliferation, exists
depending on the presence of other cell types in the culture.
|
). As the
lactotropes in mixed anterior pituitary cultures proliferated in
response to TGFß3 (Fig. 1
), and they did not in enriched cultures or
in the RC-4B/C cell line, we hypothesized that FS cells may mediate the
ability of TGFß3 to stimulate lactotropic cell proliferation. To test
this hypothesis, we determined the actions of TGFß3 in RC-4B/C cells
cocultured with FS cells. As shown in Fig. 2B, coculturing RC-4B/C
cells with FS cells resulted in proliferation of the phenotypic
lactotropes of the RC-4B/C cell line to TGFß3 (Fig. 2B). FS cells
alone did not proliferate in response to estradiol (10 nM)
with or without TGFß3 (0–10 ng/ml), as the percentage of dividing FS
cells of the total cell number did not change significantly after
TGFß3 and were 24.13 ± 1.59%, 22.75 ± 1.59%, 24.88
± 2.07%, 27.63 ± 2.14%, 23.63 ± 1.61%, and 20.63
± 2.66% for control and estradiol with 0, 0.01, 0.1, 1.0, and 10
ng/ml TGFß3 groups, respectively (P = 0.253; n =
8/group).
|
). As FS cells
caused the PRL-immunoreactive cells in the RC-4B/C cell line to
proliferate in response to TGFß3, we tested whether FS cells could
induce TGFß3 growth-promoting action on primary lactotropes. To
determine this, primary lactotropes were cocultured with FS cells and
tested for TGFß3 growth-promoting action on lactotropes. As shown in
Fig. 3, when cocultured with FS cells,
lactotropic cells showed increased proliferation in response to
TGFß3, as determined by BrdUrd incorporation.
|
). Further studies with conditioned
medium were conducted using only 1 ng/ml TGFß3.
|
Effect of bFGF on lactotropic cell proliferation
To determine whether bFGF could be a potential paracrine mediator
of TGFß3 action, the proliferative effect of bFGF on enriched
lactotropes was determined. Cultures of enriched lactotropes were
treated with various doses of bFGF in the presence of estradiol. bFGF
increased lactotropic cell proliferation, as determined by BrdUrd
incorporation, in a concentration-dependent manner in the presence of
estradiol, but this peptide had no effect on the lactotropes in the
absence of estradiol (Fig. 5A). These
data were verified using MTT assays (Fig. 5B).
|
, A and B). bFGF was undetectable in the
medium collected from enriched lactotropes (data not shown). Estradiol
had no effect on bFGF release from mixed pituitary cells and FS cells.
At concentrations between 0.001–1.0 ng/ml, TGFß3 concentration
dependently increased the release of bFGF into the culture medium from
FS cells, whereas at concentrations between 0.01–1 ng/ml TGFß3
increased bFGF from mixed anterior pituitary cells.
|
). These data were verified using a
modified MTT assay, which also demonstrated inhibition of the ability
of conditioned medium to stimulate an increase in cell number after
immunoneutralization with bFGF antibody (absorbance at 490
nM was 1.42 ± 0.068, 1.08 ± 0.032, 1.11 ±
0.053, and 0.996 ± 0.102 for lactotropes treated with conditioned
medium from TGFß3-treated FS cells that was incubated with 0, 0.1, 1,
or, 10 µg/ml bFGF antibody; P = 0.009; n =
4–8/group). The ARGG-treated group (1.25 ± 0.010) did not
display significantly different MTT metabolism compared with the group
receiving conditioned medium with no antibody (1.42 ± 0.068;
P = 0.723; n = 4–8/group). bFGF antibody did not
appear to be toxic to the cells, as there was no difference in MTT
metabolism between cultures treated directly with vehicle (1.198
± 0.062) and cultures treated with directly with 10 µg/ml bFGF
antibody (1.229 ± 0.062; P = 0.6015; n =
4/group).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
FS cells were first described in the rat pituitary by Farquar (29). FS cells are characterized by their stellate shape, with long cytoplasmic processes, and they are largely devoid of secretory granules. More recently, S-100 immunoreactivity has proven to be a reliable marker of FS cells (19, 20, 21). FS cells are present in the anterior pituitary throughout the lifespan (30) and have been detected in significant amounts in GH- and PRL-producing adenomas (31). FS cells become activated as phagocytes during estradiol exposure and the onset of prolactinoma formation (26). Estradiol has been shown to induce the expression of the immediate early gene, c-fos, in FS cells and lactotropes (32), possibly indicating direct responsiveness of FS cells to estradiol treatment. Our present data indicate yet another action of estradiol on FS cells, albeit more of a secondary effect to increased TGFß3.
FS cells have been suggested to perform several supportive functions, including regulation of ion transport, phagocytosis, tropic, and stem cell functions (32, 33, 34). More recently, FS cells have been found to act to modulate hormone secretion from other anterior pituitary cells (27, 28, 30). Studies indicate that FS cells are able to attenuate secretory responses to hypothalamic factors from anterior pituitary cells via secreted factors (27, 35). In addition, there is evidence that FS cells form gap junctions with secreting cells of the anterior pituitary and that FS cells may regulate the functions of endocrine cells via these gap-junctional complexes (36). Although we cannot discard such a possibility, the present data provide strong evidence for paracrine mediation of TGFß3 action on lactotropes, as conditioned medium from FS cells treated with TGFß3 stimulated lactotropic cell proliferation.
FS cells were implicated as a potential mediator of TGFß3-induced
lactotropic cell proliferation by the observation that in the RC-4B/C
cell line, phenotypic lactotropes did not proliferate in response to
TGFß3. The RC-4B/C cell line was established from an aged rat
pituitary adenoma and is a permanent epithelial cell line devoid of
fibroblasts (25). The RC-4B/C cell line displays immunoreactivity for
each of the hormone-secreting cell types of the anterior pituitary. For
this reason, we hypothesized that if an endocrine cell type was a
paracrine mediator of TGFß3-induced lactotropic cell proliferation,
the PRL-immunoreactive cells of the RC-4B/C cell line should
proliferate in response to TGFß3. Our data show that TGFß3
paracrine mediation of lactotropic cell proliferation did not involve
an endocrine cell type (Fig. 2A), but, rather, was mediated via FS
cells, as lactotropic phenotypes of RC-4B/C cells showed increased
proliferation in the presence of FS cells. The percentage of
lactotropes incorporating BrdUrd in cultures of RC/4-BC appears to be
lower than that in cocultures of RC/4-BC with FS cells. However, these
differences are not uniformly present. For example, control groups
between these two cultures are different, but estradiol only (0-treated
group) groups between these two cultures are similar. Furthermore,
different number of lactotropes were plated in these two cultures;
monoculture had more lactotropes because it had more RC/4-BC cells
(250,000) than coculture, which had lower numbers of lactotropes
because of lesser numbers of RC/4-BC (200,000). Hence, the addition of
the 50,000 FS cells in the coculture may have resulted in lowering the
percentage of lactotropes.
At high doses, TGFß3 inhibited lactotropic cell proliferation in the RC-4B/C cell line as it also did in cultures of enriched lactotropes. This does not appear to be a toxic effect, as in cocultures these same doses stimulated lactotropic cell proliferation. Previously, we have shown that TGFß1 inhibits lactotropic cell proliferation and that this response is mediated largely via the TGFßR-II (6, 7, 8, 15). These receptors on lactotropes appear to have a higher affinity for TGFß1 than for TGFß3, as high concentrations of TGFß3 were required to displace TGFß1 binding. Hence, it seems that the inhibition of proliferation observed at high concentrations of TGFß3 could be the result of TGFß3 binding to the TGFßR-II, which does not occur at lower concentrations.
TßR-I has been implicated to be more involved in transcriptional responses evoked by TGFß (15). Estrogen exposure reduces the number of TßR-II receptors, and these receptors are extremely reduced in transformed lactotropic cells (14, 15). Recently, it has been demonstrated that TßR-II heterozygous knockout mice develop prolactinomas in response to estradiol exposure, unlike control mice (37). Lactotropic cells with reduced levels of TßR-II display very little or no growth inhibitory response to TGFß1 (15). However, in the presence of type I receptors and very low expression of type II receptors, TGFß1 inhibits PRL secretion (15). These observations indicate that the action of TGFß3 on FS cells may be more dependent on type I receptor activation, as bFGF release from FS cells occurs under conditions where TßR-II levels are reduced. However, further experiments are needed to gain more insight into the nature of TGFß3 receptor binding on FS cells.
FS cells are known to produce several peptides that can modulate the functions and growth of neighboring cells (17, 18, 19). We studied the possible involvement of bFGF, as bFGF has previously been reported to be secreted largely from the FS cells (17) and has been implicated as a factor involved in estrogen-induced mitogenesis and tumorigenesis in the pituitary (38, 39). bFGF was first reported to be present in high concentrations in the bovine pituitary in 1974 by Gospodarowicz (40). Since its discovery, bFGF has been found to be present in a variety of tissues. bFGF is a member of the FGF family of growth factors that is comprised of proteins from at least nine distinct genes. There four mammalian FGF receptor genes that encode a complex family of transmembrane tyrosine kinases are generally composed of three Ig-like extracellular ligand-binding domains, a membrane-spanning domain, and cytoplasmic tyrosine kinase. It has been demonstrated that in pituitary adenomas there exist altered expression patterns of FGF receptor isoforms and subtypes that may determine hormonal and proliferative responses to FGFs (41).
The presence of bFGF has been reported in human pituitary adenomas (42). Baird et al. demonstrated that estradiol treatment results in a doubling of bFGF content in the anterior pituitary of Fischer-344 rats (43). bFGF is recognized as an important factor in tumor formation as an angiogenic factor in the anterior pituitary (44). Recently, bFGF has also been implicated as a mitogenic factor in a lactotrope-derived tumor cell line under estrogenic conditions (39). In this study bFGF is also a proliferative factor in lactotropes in primary culture. Our data show that FS cells are the primary source of bFGF, as detectable levels of this peptide are observed in the medium of FS cell cultures and mixed population pituitary cell cultures, but not in enriched lactotropic cell cultures. Comparison of the amount of bFGF secreted per cell between mixed pituitary cells and FS cells indicated that FS cells culture produce 10- to 12-fold more protein per cell than mixed pituitary cells, suggesting that approximately 8–10% cells in mixed pituitary cultures may be FS cells. Additionally, these data show that the secretion of bFGF may be secondary to the increase in TGFß3 that occurs as a result of estradiol exposure (8). bFGF only stimulated lactotropic cell proliferation in the presence of estradiol. The need for estradiol to be present for bFGF to cause proliferation in lactotropes may be attributable to the fact that estradiol increases bFGF receptor levels in lactotropes (39). This may explain at least in part why there is a more robust response to TGFß3 in the presence of estradiol compared with that in its absence (8).
In several tissues the growth of cells depends not only on the mitogenic stimulus, but also on cell to cell interactions. In uterine, ovarian, and mammary tissues, the communication with mesenchymal cells facilitates the growth of epithelial cells (45, 46, 47). In some cell types, in which various isoforms of TGFß stimulate cell proliferation, the actions of these peptides on the cells appear to be indirect, via increasing the production of other growth factors (reviewed in Refs. 11, 13). The present data indicate that, similar to some other estrogen-responsive tissues, the pituitary is another site where TGFß action is mediated by cell to cell interactions. To the best of our knowledge, this is the first report of TGFß action on FS cells as well as the first evidence indicating that TGFß increases bFGF release in the anterior pituitary.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Present address: Vollum Institute, Oregon Health Science University,
L-474, Portland, Oregon 97201.
Received April 7, 1999.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-Transforming growth factor in the bovine pituitary gland, secretion
by dispersed cells and immunohistochemical localization. Endocrinology 121:1412–1415[Abstract]
on hormone secretion in rat anterior pituitary cell
cultures. Endocrinology 130:3537–3546[Abstract]
This article has been cited by other articles:
 |
|
 |
|
  M. Ishida, W. Takahashi, S. Itoh, S. Shimodaira, S. Maeda, and J. Arita Estrogen Actions on Lactotroph Proliferation Are Independent of a Paracrine Interaction with Other Pituitary Cell Types: A Study Using Lactotroph-Enriched Cells Endocrinology, July 1, 2007; 148(7): 3131 - 3139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vlotides, M. Cruz-Soto, T. Rubinek, T. Eigler, C. J. Auernhammer, and S. Melmed Mechanisms for Growth Factor-Induced Pituitary Tumor Transforming Gene-1 Expression in Pituitary Folliculostellate TtT/GF Cells Mol. Endocrinol., December 1, 2006; 20(12): 3321 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Liu, W. Ding, J. Neiman, and K. M. Mulder Requirement of Smad3 and CREB-1 in Mediating Transforming Growth Factor-beta (TGFbeta) Induction of TGFbeta3 Secretion J. Biol. Chem., October 6, 2006; 281(40): 29479 - 29490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Sarkar, K. Chaturvedi, S. Oomizu, N. I. Boyadjieva, and C. P. Chen Dopamine, Dopamine D2 Receptor Short Isoform, Transforming Growth Factor (TGF)-{beta}1, and TGF-{beta} Type II Receptor Interact to Inhibit the Growth of Pituitary Lactotropes Endocrinology, October 1, 2005; 146(10): 4179 - 4188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kabir, K. Chaturvedi, L. S. Liu, and D. K. Sarkar Transforming Growth Factor-{beta}3 Increases Gap-Junctional Communication among Folliculostellate Cells to Release Basic Fibroblast Growth Factor Endocrinology, September 1, 2005; 146(9): 4054 - 4060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chaturvedi and D. K. Sarkar Role of Protein Kinase C-Ras-MAPK p44/42 in Ethanol and Transforming Growth Factor-{beta}3-Induced Basic Fibroblast Growth Factor Release from Folliculostellate Cells J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1346 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chaturvedi and D. K. Sarkar Mediation of Basic Fibroblast Growth Factor-Induced Lactotropic Cell Proliferation by Src-Ras-Mitogen-Activated Protein Kinase p44/42 Signaling Endocrinology, April 1, 2005; 146(4): 1948 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oomizu, K. Chaturvedi, and D. K. Sarkar Folliculostellate Cells Determine the Susceptibility of Lactotropes to Estradiol's Mitogenic Action Endocrinology, March 1, 2004; 145(3): 1473 - 1480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chaturvedi and D. K. Sarkar Involvement of Protein Kinase C-Dependent Mitogen-Activated Protein Kinase p44/42 Signaling Pathway for Cross-Talk between Estradiol and Transforming Growth Factor-{beta}3 in Increasing Basic Fibroblast Growth Factor in Folliculostellate Cells Endocrinology, February 1, 2004; 145(2): 706 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Gomez and J. A. Balsa Autocrine/Paracrine Action of Pituitary Vasoactive Intestinal Peptide on Lactotroph Hyperplasia Induced by Estrogen Endocrinology, October 1, 2003; 144(10): 4403 - 4409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Chapman, M. J. Epton, J. C. Buckingham, J. F. Morris, and H. C. Christian Evidence for a Role of the Adenosine 5'-Triphosphate-Binding Cassette Transporter A1 in the Externalization of Annexin I from Pituitary Folliculo-Stellate Cells Endocrinology, March 1, 2003; 144(3): 1062 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Bilezikjian, A. M. O. Leal, A. L. Blount, A. Z. Corrigan, A. V. Turnbull, and W. W. Vale Rat Anterior Pituitary Folliculostellate Cells Are Targets of Interleukin-1{beta} and a Major Source of Intrapituitary Follistatin Endocrinology, February 1, 2003; 144(2): 732 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Renner, P. Lohrer, L. Schaaf, M. Feirer, K. Schmitt, C. Onofri, E. Arzt, and G. K. Stalla Transforming Growth Factor-{beta} Stimulates Vascular Endothelial Growth Factor Production by Folliculostellate Pituitary Cells Endocrinology, October 1, 2002; 143(10): 3759 - 3765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kawakami, Y. Fujii, Y. Okada, and S. J. Winters Paracrine Regulation of FSH by Follistatin in Folliculostellate Cell-Enriched Primate Pituitary Cell Cultures Endocrinology, June 1, 2002; 143(6): 2250 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
