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*
Institut National de la Santé et de la Recherche Médicale U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker, Paris, France;
Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia; and
Institut National de la Santé et de la Recherche Médicale U-429, Hopital Necker Enfants-Malades, Paris, France
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Other earlier studies using in vivo models of pituitary depletion suggested a role for PRL in lymphohemopoietic development. Hypophysectomized rats present symptoms of immunosuppression such as lymphopenia and impaired humoral and cellular Ag responses (3). Bromocryptine, a dopamine receptor agonist, causes PRL depletion and thereby mimics hypophysectomy. Administration of bromocryptine is also associated with a decreased Ab response following immunization with SRBCs (4). The effects of hypophysectomy or bromocryptine on certain immune responses can be reversed by exogenous PRL administration, implying a role for PRL in immune regulation. However, these models do not allow for complete PRL depletion, because a number of extrapituitary sites of PRL synthesis have also been described. In addition, multiple endocrine pathways are potentially altered in these experimental models, which renders their interpretation difficult.
Subsequent in vitro models have indicated that PRL can induce lymphocyte proliferation, although these findings are controversial (reviewed in Ref. 5). In addition, PRL has been shown to increase the expression of CD25, of the erythropoietin receptor, and of its own receptor. In NK cells, PRL increases DNA synthesis and cytotoxicity against specific target cells (6). PRL inhibits T cell apoptosis under certain conditions and enhances Ab production by mature B cells (7). Finally, a series of publications have indicated a role for nuclear PRL in the T cell response to IL-2 (8). Overall, the body of literature on PRL and its effects on the immune system has suggested several important immunomodulatory roles for this cytokine; however, some of them appear to be contradictory, particularly with regard to the in vitro studies, which indicate either an immunostimulatory or an immunosuppressive role for PRL (reviewed in Ref. 5).
Recently, renewed attention has been given to the potential actions of
PRL on the immune system. Montgomery et al. identified a PRL-like
molecule that is produced and secreted by lymphocytes (9, 10). These authors suggested that lymphocytes might therefore
use PRL in an autocrine fashion. Indeed, in all species analyzed, the
expression of the PRLR appears almost ubiquitous, and several studies
have aimed at determining the level of expression of the PRLR on
immunocompetent cells. Classical approaches involving radiolabeled
ligand binding assays have indicated that the number of PRLR molecules
present on the lymphocyte cell surface is quite low, and often at the
limits of detection (
300 receptors per cell (11)). In
contrast, levels of IL-2R or IL-7R approach 104
receptors per lymphoid cell. More recently, lymphocyte PRLRs have been
evaluated using biotinylated ligands or specific mAbs in FACS analysis
(12). These studies demonstrated the expression of PRLR on
all lymphoid subsets, but did not allow the exact number of PRL binding
sites on these different cell populations to be assessed.
Our laboratory has recently generated a PRLR-deficient mouse model by gene-targeting techniques. In this mouse strain, the PRLR has been invalidated in all tissues. Using immunoprecipitation of PRLR followed by immunoblotting, we could not detect PRLR proteins in extracts from liver and bone cells from knockout (KO) animals (13, 14). In addition, no significant binding of PRLR-specific ligands (growth hormone or PRL) was detected in liver microsome preparations from PRLR-/- mice. Therefore, these mice are useful to analyze any potential role of PRLR signaling in developmental processes. In this report, we have assessed the role of PRL/PRLR pathways in lymphocyte activation and maturation.
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Materials and Methods |
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Mice carrying a null mutation in the PRLR on a mixed (129Ola x C57BL/6) background have been described previously (13) and were maintained in a specific pathogen-free animal facility. C57BL/6 PRLR-/- mice were obtained by backcrossing the PRLR mutation for eight generations onto the C57BL/6 background followed by intercrossing to obtain homozygous mutant mice. Simultaneous identification of the wild-type (WT) or mutated genomic PRLR loci was performed by a three-primer PCR using DNA isolated from tails snips according to standard protocols. The following primers were used: WT forward, 5'-GAGAAAAACACCTATGAATGT-3'; Neo forward, 5'-CCAGTCCCTTCCCGCTTCAGT-3'; common reverse, 5'-GAAGAGCAAGATCTCAAGAAC-3'. Conditions for the PCR were 5' denaturation at 94°C followed by 35 cycles consisting of 45 s at 94°C, 1 min at 57°C, and 45 sec at 72°C. Using these conditions, the WT locus generates a 350-bp fragment, whereas the mutant allele gives a 580-bp fragment. All mice were studied between 3 and 10 wk of age, except in specific experiments as mentioned in the text.
Cell isolation and in vitro proliferation analysis
Organs were removed aseptically, and single-cell suspensions were prepared in sterile medium using a mesh filter. After lysis of contaminating erythrocytes by hypotonic NH4Cl, cells were resuspended and counted; viability was determined using trypan blue dye exclusion. For mitogenic assays, splenocytes were cultured at 2 x 105 cells/well in flat-bottom, 96-well plates in RPMI 1640 medium supplemented with 10% FCS with or without Con A (2.5 µg/ml) and cytokines (IL-2 or IL-7 at 20 ng/ml) for 3 days. For mixed lymphocyte reaction, 2500 rad-irradiated allogeneic (from BALB/c mice, H-2d) or syngeneic (from C57BL/6 mice, H-2b) splenocytes were used as stimulator cells and cocultured with equal numbers (105 cells) of responder cells in round-bottom, 96-well plates for 5 days. In all experiments, cells were pulsed with 1 µCi of [3H]thymidine during the final 8 h of culture.
Immunofluorescence analysis
Cells were resuspended in PBS/1% FCS/0.01% sodium azide
(washing buffer). Abs against the following cell surface Ags were used
for immunofluorescence analysis (all from PharMingen, San Diego, CA) as
FITC, PE, or tricolor conjugates: CD4, CD8, CD24 (heat-stable Ag), CD25
(IL-2R
), CD43, CD45R (B220), CD69, TCRß, IgM, IgD, and NK1.1.
Staining combinations are indicated in the figure legends. Cells
(5 x 105) were initially incubated for 20
min at room temperature with anti-FcRII/III Ab (2.4G2) to block
nonspecific reactivity. Incubation was then performed with specific Abs
for 20 min on ice before extensive washing. Labeled cells were analyzed
on a FACScan flow cytometer using Lysis II software (Becton Dickinson,
Mountain View, CA).
Determination of serum Ig levels and Ag-specific Ig responses
For total serum Ig concentrations, 8- to 10-wk-old mice were
analyzed. Whole blood was collected from retroorbital plexus, and
plasma was stored at -20°C before analysis. Serum Ig isotypes were
determined by ELISA as described previously (15). For T
cell-dependent Ig responses, mice were injected i.p. with
alum-precipitated 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken
-globulin (CG) (NP-CG) (100 µg per mouse). After 7 and 14 days, Ig
isotypes and concentrations were determined for NP-CG-binding Abs,
respectively, by a direct plate binding assay as described
previously.
Tumor cell cytotoxicity assays
Mice were injected with poly(IC) (100 µg in 1 ml normal saline) at 48 h before sacrifice. Unfractionated splenocytes from PRLR-/- mice or their normal littermates were cocultured with 5000 51Cr-labeled YAC-1 target cells at varying E:T ratios for 4 h at 37°C with 5% CO2. Radioactivity was measured in the supernatants, and specific lysis was determined according to the following formula: % lysis = ([test cpm - control cpm]/[max cpm - control cpm]). For in vivo tumor rejection studies, mice (H-2b) were injected i.p. with 107 cells from the allogeneic tumor line P815 (H-2d). The animals were then monitored daily for the appearance of tumors, and survival over a period of 60 days was assessed.
Listeria monocytogenes (L.m.) infection
Groups of five PRLR-/- mice or control mice were injected i.v. with 5 x 103 cfu of L.m. as described previously (16); survival was monitored for a period of 6 wk. For early innate responses to L.m., mice were infected i.v. with 3 x 103 cfu, and the total L.m. burden in the liver and spleen were determined on day 2 postinfection by plating whole organ homogenates on tryptic soy broth plates (16).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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13 mo of age (data not shown). The spleen and thymus of adult (6- to 8-wk-old) PRLR-/- mice were similar in weight and cellularity to those of WT control mice (60 ± 8 x 106 cells vs 50 ± 12 x 106 cells, respectively, for spleen WT and PRLR-/-; 87 ± 11 x 106 cells vs 98 ± 15 x 106 cells, respectively, for thymus WT and PRLR-/-). Histological examination of these tissues, as well as of the intestinal epithelia, failed to reveal obvious structural abnormalities (data not shown).
B cell development in PRLR-/- mice
Total numbers of nucleated bone marrow (BM) cells were similar in
both PRLR+/+ and PRLR-/-
mice (20.2 ± 4 x 106 cells vs
22.4 ± 5 x 106 cells, respectively,
for WT and PRLR-/-), as were the percentages of
B220+ lymphoid cells (Fig. 1
A). We found that the
percentages of immature
B220+/IgM- pro-/pre-B
cells were not significantly decreased in
PRLR-/- mice compared with controls. The early
B cells expressed normal patterns of CD43 and CD24 (heat-stable Ag)
(data not shown). More mature IgM+ B cells in the
BM were also normally represented (Fig. 1A). These results
demonstrate that the absence of PRLR has no major deleterious effects
on the generation of B cell precursors in the BM.
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B). These cells expressed normal levels of IgM and IgD.
Moreover, the ratio of newly generated B cells
(IgMhigh/IgDlow) and
mature, recirculating B cells
(IgMlow/IgDhigh) was
unchanged in the absence of the PRLR.
IgMhigh/IgDlow B cells did
not appear to be activated as evidenced by their lack of CD25 and CD69
expression (data not shown). T cell development in PRLR-/- mice
Thymocyte differentiation was not impaired in
PRLR-/- mice in that the percentages of
CD4-CD8- double-negative,
CD4+CD8+ double-positive,
CD4+ single-positive, and
CD8+ single-positive thymocytes were similar to
control mice (Fig. 2A). The
expression of TCR ß-chain was normal (Fig. 2B), suggesting
that PRLRs do not play a major role in pre-TCR or TCR selection
pathways. With regard to early thymocyte development, earlier reports
suggested that PRL decreased thymic cellularity in vivo
(17) and induced a preferential development of mature
CD4+ thymocytes (18). We examined
early T cell precursors from PRLR-/- mice by
analyzing CD44 and CD25 expression on
CD3-CD4-CD8-
thymocytes. No differences in the differentiation of pro- or pre-T
cells could be discerned between PRLR-/- and
control thymocytes (Fig. 2C). Finally, no age-related
changes in thymocyte development were noted when comparing newborn, 3-
to 4-wk-old, or 6- to 8-wk-old PRLR-/- and
control mice (data not shown).
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ß-expressing cells were found in the spleen and lymph nodes of
adult PRLR-/- mice at normal frequencies (Fig. 3A).
TCR
+ cells were also present normally among
PRLR-/- splenocytes (data not shown). Previous
reports demonstrated that CD25 expression was increased in the presence
of PRL (19). In contrast, we found a normal constitutive
expression of CD25 on a small subpopulation of peripheral splenic
CD4+ T cells (20) from control and
PRLR-/- mice (Fig. 4A). Taken together, these
data rule out any essential role for PRLRs in normal T cell
development.
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Previous reports have indicated that PRL depletion by
hypophysectomy or by treatment with bromocryptine can provoke marked
abnormalities in humoral immune responses (4). To analyze
any effect of PRLR deficiency on B cell Ig production, sera from
8-wk-old PRLR-/- and control mice were analyzed
for total Ig levels. No significant differences were observed in the
levels of IgM, all IgG subclasses, IgA, or IgE (data not shown). We
subsequently sought to determine whether
PRLR-/- mice could generate normal Ag-specific
Ig responses in vivo. WT or mutant mice were immunized with NP-CG to
elicit T-dependent Ig responses. NP-specific IgM and switched IgG
levels were detected in both types of mice (Fig. 5). Ab responses of WT and mutant mice
were quantitatively and kinetically indistinguishable. Thus, in
contrast to previous reports, absence of PRLR signaling does not appear
to perturb normal B cell Ig responses.
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The secretion of a PRL-like molecule by lymphocytes has led to the
speculation that PRL could act as an autocrine factor for lymphocyte
growth (9). Clevenger et al. have further presented a
model in which PRL signaling via its receptor plays a role in the
mitogen-induced CD25 expression necessary for IL-2 mediated
proliferation (21). To evaluate a role for PRLR signaling
in T cell mitogen responses in vitro, we stimulated splenocytes (or
lymph node cells) from control or PRLR-/- mice
with Con A and examined the patterns of CD25 expression. No qualitative
or quantitative differences in the levels of induction of CD25 could be
observed between these mice (Fig. 4B). The proliferation of
Con A-activated splenocytes was increased by the addition of exogenous
cytokines (including IL-2 or IL-7), demonstrating that PRLR-deficient
lymphocytes are fully competent to proliferate in this setting (Fig. 6). These results call into question the
role of the proposed PRL/PRLR autocrine loop during in vitro
mitogen-induced proliferation.
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, both PRLR-/-
and control animals demonstrated normal allogeneic responses and only
background levels of proliferation against syngeneic cells.
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NK and NK-T cell development were examined in
PRLR-/- mice on the C57BL/6 background.
Compared with control animals, PRLR-/- mice
demonstrated normal percentages of liver NK1.1+
CD3- NK cells and NK1.1+
CD3+ NK-T cells (Fig. 3B). After in
vivo NK cell priming with poly(IC), unfractionated splenocytes were
tested for their ability to lyse the NK-sensitive target cell YAC-1.
Both control and PRLR-/- splenocytes were
capable of specifically lysing YAC-1 cells (35% specific lysis vs 32%
specific lysis at a 100:1 E:T ratio, respectively, for
PRLR-/- and controls, see Fig. 8). In vivo antitumor responses were
examined after an i.p. injection of allogeneic P815 mastocytoma cells.
PRLR-/- animals successfully eliminated tumor
cells, with no evidence of palpable lesions over the length of the
experiment (>60 days; data not shown). Taken together, these results
suggest that PRLR signaling is not required for NK differentiation.
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Infection with L.m. serves as the prototypic model for immune responses against intracellular pathogens (reviewed in Ref. 22). Immunity to L.m. in normal animals proceeds in two stages: the initial innate immune response involving macrophages, NK cells, and neutrophils followed by a sterilizing adaptive immune response requiring T and B cells. In contrast, infection of immunodeficient animals can result in either 1) rapid, lethal dissemination of L.m. in a matter of days or 2) chronic listeriosis with mortality after 2–3 wk. Because earlier reports have implicated a role for PRL signaling in the response to L.m. (23), we compared sublethal (3 x 103 cfu, i.v.) L.m. infection in PRLR-/- and control animals. No deaths of PRLR KO or control mice were observed during the period of 6 wk after L.m. infection (data not shown). PRLR-/- mice showed normal innate (day 2) responses to L.m., because total liver or spleen cfu burdens were similar to control mice (4.1 ± 0.6 x 104 cfu/liver and 4.5 ± 0.5 x 104 cfu/spleen vs 4.0 ± 0.9 x 104 cfu/liver and 4.5 ± 0.6 x 104 cfu/spleen, respectively, for PRLR-/- and controls). These results rule out an essential role for PRL signaling in normal immune responses to L.m.
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Discussion |
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Such discrepancies are illustrated by comparing our data with initial reports using hypophysectomized animals in which the Ig production in response to T-dependent Ags such as SRBCs is abrogated (3). From these initial studies, it is not clear whether the defect directly affects B cells or is due to an indirect effect on T cell help. In contrast, our study clearly establishes that PRLR-/- animals exhibit a normal B cell response to T-dependent Ags.
A second example involves the reported role of PRL in normal immunity
to L.m. Bernton et al. reported that hypoprolactinemia resulting from
bromocryptine treatment of mice was associated with increased
susceptibility to L.m within 7 days postinfection (23). In
this report, the authors further suggested that impaired production of
macrophage-activating factors (such as T cell-derived IFN-) could
explain these observations. In support of this hypothesis, the authors
indicated that bromocryptine-treated mice had an impaired proliferative
response to the T cell mitogen Con A. Using our PRLR KO model, we
have reassessed the role of PRL signaling in immunity to L.m. In
contrast to Bernton et al., we find that the resistance of
PRLR-/- mice to sublethal L.m. infection is
similar to that of control mice. The fact that
PRLR-/- mice have normal day 2 liver and spleen
L.m burdens indicates that PRL is not required for generating
macrophage effector functions, which are the hallmark of innate
responses to this pathogen. Normal day 2 responses also indicate that
NK cell-derived IFN- production has occurred at that time. T cells
are only required during the adaptive later phases of L.m. infection
(reviewed in Ref. 22), and normal T cell function in the
absence of PRLRs is suggested by the long-term survival of infected
PRLR-/- mice. Finally, it should be emphasized
that an important role for PRL in normal Con A-induced T cell
proliferation is unlikely, because PRLR-/-
lymphocytes respond to this mitogen in vitro similarly to control cells
(Fig. 5)
The discrepancies between numerous previous reports (5) and the data presented in this study can probably be best accounted for by the differences between the experimental models. As stated above, hypophysectomized animals or bromocryptine-treated mice present pituitary deficiencies encompassing several endocrine pathways. In contrast, our KO model allows direct evaluation of the role of PRL in the immune system. In a similar manner, Montecino-Rodriguez et al. have shown that the B cell defects in Snell-Dwarf mice are most likely due to the absence of thyroid hormone (30), whereas previous reports had left undetermined the exact participation of other pituitary hormones in this defect (31, 32).
An alternative hypothesis for the absence of the immune system alterations in PRLR KO mice would be the existence of another receptor for PRL. Following this scenario, PRL signals would still be possible in the absence of the known PRLR, being transmitted through this alternative receptor. Possible candidates for this "second receptor model" include the growth hormone receptor (GHR), the placental lactogen (PL) receptor, or another as yet unidentified PRLR-like molecule. A role for GHR in transmitting PRL signals appears very unlikely, because in all species analyzed, the GHR is unable to bind PRL (33, 34). We are currently generating double KO animals, deficient for both GHRs and PRLRs, to further analyze the interactions between these two signaling systems. Although a potential PL binding site has been suggested (35, 36), a specific PL receptor has not been identified to date. Finally, despite efforts from several laboratories, experimental evidence for the existence of a second PRLR has not been obtained. The existence of another PRLR would also imply a differential regulation and expression in hemopoietic cells, but not in the mammary gland or the ovary and uterus, where deletion of the known PRLR gene leads to strong phenotypes (13).
As for most members of the cytokine receptor superfamily, the PRLR
signaling cascade activates members of the JAK-STAT family. Still,
cytokine specificity does not appear to be controlled by JAK-STAT
molecules. For example, JAK2, which is activated by PRL, is also
involved in signaling through a large number of other cytokine
receptors, including the erythropoietin receptor, IFN-R, IL-3R,
GM-CSF receptor, IL-5R, thrombopoietin receptor, and GHR. Additional
pathways have also been described for the PRLR, such as the
ras/raf/mitogen-activated protein kinase pathway; however, these
pathways are also not restricted to the PRLR (37, 38). The
existence of these overlapping signaling mechanisms strongly suggests
the occurrence of redundancy between members of the cytokine receptor
superfamily. However, our previous observations using PRLR KO mice have
shown that PRL is essential for reproduction or lactation, and that
compensatory mechanisms do not take place in these systems
(13). In contrast, our current data demonstrate that if
PRL has an immunomodulatory role, its function is completely
compensated. This is not the case for all cytokines, because recent
reports have shown that deficiencies in IL-4 or IL-7 can have
deleterious effects on the immune system (39, 40) without
any possible compensation. Moreover, recent literature strongly
suggests that JAK proteins have nonredundant roles during the induction
of biological effects in response to specific cytokines
(41). Finally, it would be tempting to speculate that the
PRLR could signal using a pleiotropic system, in which the reproductive
and lactating systems would rely on the JAK-STAT pathway, whereas
alternative molecules would be recruited in immunocompetent cells.
However, this hypothesis seems to contradict the body of literature
defining the essential role of the JAK-STAT cascade, even in the
lymphoid tissues (42, 43).
Initial in vitro analysis of the various cytokine/cytokine receptor systems had suggested that pathway redundancy existed for this family of molecules, and their fine specificities remained unknown. The establishment of genetically defined in vivo models has allowed investigators to reassess the biological role of various cytokines and to better evaluate their physiological functions. Using our KO model, we have clearly established that PRL is not essential for the proper development and function of the mouse immune system.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Paul A. Kelly, Institut National de la Santé et de la Recherche Médicale U-344, Endocrinologie Moléculaire, Faculté de Médecine Necker, 75730 Paris Cedex 15, France. E-mail address:
3 Abbreviations used in this paper: PRL, prolactin; PRLR, PRL receptor; GHR, growth hormone receptor; PL, placental lactogen; JAK, Janus kinase; KO, knockout; BM, bone marrow; L.m., Listeria monocytogenes; NP, 4-hydroxy-3-nitrophenyl acetyl; CG, chicken -globulin; WT, wild type.
Received for publication March 5, 1999. Accepted for publication April 26, 1999.
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References |
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production and innate immunity during Listeria monocytogenes infection in the absence of NK cells. J. Immunol. 161:5600. chain, resistance to clonal deletion, and IL-2 dependency. Int. Immunol. 10:371.This article has been cited by other articles:
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  S. Semprini, S. Friedrichsen, C. V. Harper, J. R. McNeilly, A. D. Adamson, D. G. Spiller, N. Kotelevtseva, G. Brooker, D. G. Brownstein, A. S. McNeilly, et al. Real-Time Visualization of Human Prolactin Alternate Promoter Usage in Vivo Using a Double-Transgenic Rat Model Mol. Endocrinol., April 1, 2009; 23(4): 529 - 538. [Abstract] [Full Text] [PDF]
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 C. Huang, F. Snider, and J. C. Cross Prolactin Receptor Is Required for Normal Glucose Homeostasis and Modulation of {beta}-Cell Mass during Pregnancy Endocrinology, April 1, 2009; 150(4): 1618 - 1626. [Abstract] [Full Text] [PDF]
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 J. Cohen-Solal, V Jeganathan, L Hill, D Kawabata, D Pinto-Rodriguez, C Grimaldi, and B Diamond Hormonal regulation of B-cell function and systemic lupus erythematosus Lupus, June 1, 2008; 17(6): 528 - 532. [Abstract] [PDF]
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 Z. Kang, G. Y. Bedecarrats, and D. Zadworny Expression Patterns of the Prolactin Receptor Gene in Chicken Lymphoid Tissues During Embryogenesis and Posthatch Period Poult. Sci., November 1, 2007; 86(11): 2404 - 2412. [Abstract] [Full Text] [PDF]
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M. J. LeBaron, T. J. Ahonen, M. T. Nevalainen, and H. Rui In Vivo Response-Based Identification of Direct Hormone Target Cell Populations Using High-Density Tissue Arrays Endocrinology, March 1, 2007; 148(3): 989 - 1008. [Abstract] [Full Text] [PDF]
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 T. Matsutani, T. S. A. Samy, L. W. Rue III, K. I. Bland, and I. H. Chaudry Transgenic prolactin-/- mice: effect of trauma-hemorrhage on splenocyte functions Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1109 - C1116. [Abstract] [Full Text] [PDF]
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 C. Dosiou and L. C. Giudice Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives Endocr. Rev., February 1, 2005; 26(1): 44 - 62. [Abstract] [Full Text] [PDF]
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 K Horiguchi, S Yagi, K Ono, Y Nishiura, M Tanaka, M Ishida, and T Harigaya Prolactin gene expression in mouse spleen helper T cells J. Endocrinol., December 1, 2004; 183(3): 639 - 646. [Abstract] [Full Text] [PDF]
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 A. M. Corbacho, G. Valacchi, L. Kubala, E. Olano-Martin, B. C. Schock, T. P. Kenny, and C. E. Cross Tissue-specific gene expression of prolactin receptor in the acute-phase response induced by lipopolysaccharides Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E750 - E757. [Abstract] [Full Text] [PDF]
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T. Fujikawa, H. Soya, K. L. K. Tamashiro, R. R. Sakai, B. S. McEwen, N. Nakai, M. Ogata, I. Suzuki, and K. Nakashima Prolactin Prevents Acute Stress-Induced Hypocalcemia and Ulcerogenesis by Acting in the Brain of Rat Endocrinology, April 1, 2004; 145(4): 2006 - 2013. [Abstract] [Full Text] [PDF]
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N. Krishnan, O. Thellin, D. J. Buckley, N. D. Horseman, and A. R. Buckley Prolactin Suppresses Glucocorticoid-Induced Thymocyte Apoptosis in Vivo Endocrinology, May 1, 2003; 144(5): 2102 - 2110. [Abstract] [Full Text] [PDF]
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 S. Zhou, F. R. A. Cagampang, J. A. Stirland, A. S. I. Loudon, and S. J. Hopkins Different Photoperiods Affect Proliferation of Lymphocytes but Not Expression of Cellular, Humoral, or Innate Immunity in Hamsters J Biol Rhythms, October 1, 2002; 17(5): 392 - 405. [Abstract] [PDF]
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 L.-Y. Yu-Lee Prolactin Modulation of Immune and Inflammatory Responses Recent Prog. Horm. Res., January 1, 2002; 57(1): 435 - 455. [Abstract] [Full Text] [PDF]
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A Stevens, D W Ray, J Worthington, and J R. Davis Polymorphisms of the human prolactin gene--implications for production of lymphocyte prolactin and systemic lupus erythematosus Lupus, October 1, 2001; 10(10): 676 - 683. [Abstract] [PDF]
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A R Buckley Prolactin, a lymphocyte growth and survival factor Lupus, October 1, 2001; 10(10): 684 - 690. [Abstract] [PDF]
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L.-y. Yu-Lee Stimulation of interferon regulatory factor-1 by prolactin Lupus, October 1, 2001; 10(10): 691 - 699. [Abstract] [PDF]
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L. Welniak, S. Richards, and W. Murphy Effects of prolactin on hematopoiesis Lupus, October 1, 2001; 10(10): 700 - 705. [Abstract] [PDF]
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L Matera, M Mori, and A Galetto Effect of prolactin on the antigen presenting function of monocyte-derived dendritic cells Lupus, October 1, 2001; 10(10): 728 - 734. [Abstract] [PDF]
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S E Walker Bromocriptine treatment of systemic lupus erythematosus Lupus, October 1, 2001; 10(10): 762 - 768. [Abstract] [PDF]
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A. J. Craven, C. J. Ormandy, F. G. Robertson, R. J. Wilkins, P. A. Kelly, A. J. Nixon, and A. J. Pearson Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice Endocrinology, June 1, 2001; 142(6): 2533 - 2539. [Abstract] [Full Text] [PDF]
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S E Walker Treatment of systemic lupus erythematosus with bromocriptine Lupus, March 1, 2001; 10(3): 197 - 202. [Abstract] [PDF]
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 K. A. McClellan, F. G. Robertson, J. Kindblom, H. Wennbo, J. Törnell, B. Bouchard, P. A. Kelly, and C. J. Ormandy Investigation of the Role of Prolactin in the Development and Function of the Lacrimal and Harderian Glands Using Genetically Modified Mice Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 23 - 30. [Abstract] [Full Text]
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W. Savino and M. Dardenne Neuroendocrine Control of Thymus Physiology Endocr. Rev., August 1, 2000; 21(4): 412 - 443. [Abstract] [Full Text] [PDF]
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K. Dorshkind and N. D. Horseman The Roles of Prolactin, Growth Hormone, Insulin-Like Growth Factor-I, and Thyroid Hormones in Lymphocyte Development and Function: Insights from Genetic Models of Hormone and Hormone Receptor Deficiency Endocr. Rev., June 1, 2000; 21(3): 292 - 312. [Abstract] [Full Text]
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