Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of neonatal thymectomy, at 3 days of age, on parameters of the reproductive axis were examined in male and female Sprague-Dawley rats. Gonadal and accessory sex tissue (male: epididymis, seminal vesicle, and ventral prostate; female: uterus) weights as well as anterior pituitary, spleen, and adrenal weights were determined in the thymectomized and sham-thymectomized animals at 20, 30, 40, 50, 60, and 90 days of age. Plasma gonadotropin concentrations as well as pituitary content of the gonadotropins and prolactin were assessed at each of these time intervals. No significant difference in gonad and accessory sex tissue weights was detected in thymectomized versus sham-operated controls at each of these times. Adrenal weights were increased in thymectomized animals compared with controls at 50 days of age and older in male rats and at 90 days in females. Spleen weights were decreased in the thymectomized males at 50 and 60 days of age. Thymectomy did not affect the spleen weight of females. Plasma concentrations of gonadotropins were unaffected in thymectomized males but were altered in females during the pre- and peripubertal period (Days 20-40). Vaginal opening, however, occurred at the same time in the thymectomized and control females. Pituitary gonadotropin and prolactin content were unaffected by thymectomy of the females, except at 90 days when pituitary luteinizing hormone (LH) content was lower in thymectomized than in control animals. LH and prolactin content were significantly reduced in the males at 60 and 90 days of age. These results demonstrate that there are sexual differences in the effects of thymectomy on parameters of the reproductive axis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation by neonatal thymectomy of the reproductive axis in male and female rats during development. 313 Jan 12

This study examined the effect of chronic cocaine exposure on selected immune parameters in pregnant rats. Cocaine hydrochloride, 60 mg/kg, was administered by i.p. injection as a divided daily dose on gestation days 8 to 19. This cocaine treatment regimen did not result in any change in maternal body weight, spleen and thymus body weight ratios or lymphocyte recovery from these organs. Cocaine treatment had no effect on the plasma levels of prolactin, growth hormone and insulin-like growth factor-1; hormones with immunoregulatory potential. In contrast, the plasma immunoglobulin G concentration in cocaine-treated animals was 48% higher (P < .05) than in control animals. Spleen lymphocytes and thymocytes were isolated and evaluated for their proliferative responses in vitro to a panel of T and B cell mitogens. Lymphocytes from cocaine-treated animals showed no significant differences in proliferative responses to concanavalin A (conA), phytohemagglutinin, pokeweed mitogen, interleukin-2 or lipopolysaccharide. The ability of conA-stimulated spleen lymphocytes to synthesize and secrete prolactin-immunoreactive proteins was further assessed by Western immunoblotting. We found that conA-stimulated spleen lymphocytes from cocaine-treated animals showed significantly decreased levels of intracellular and secreted 44,000-mw prolactin-immunoreactive proteins. In contrast, conA-stimulated spleen lymphocytes from control and cocaine-treated groups secreted equivalent amounts of the cytokine interleukin-2. In conclusion, chronic administration of cocaine to female rats during pregnancy significantly altered serum immunoglobulin G levels and lymphocyte production of prolactin-immunoreactive proteins in the absence of changes in lymphocyte proliferation in response to mitogens.
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PMID:Evaluation of immune parameters and lymphocyte production of prolactin-immunoreactive proteins after chronic administration of cocaine to pregnant rats. 862 20

The induction of donor-specific unresponsiveness in allograft recipients would lessen the need for chronic immunosuppression and its concomitant morbidities. In view of recognized interactions between the immune and neuroendocrine systems, we hypothesized that manipulating prolactin (PRL) levels might enhance the immunosuppressive effects of donor-specific blood transfusions. Bromocriptine (BR) and domperidone (DOM), administered via osmotic pumps, were used to inhibit or increase pituitary PRL secretion, respectively, in male LEW rats treated with donor-specific transfusions (DST, Day -1), cyclosporine (CsA, 5 mg/kg, Days -1 to +1), and receiving ACI heart allografts. Neither compound had direct effects on lymphoid cells in vitro. BR had no effects on graft survival in rats treated with either BT or CsA (BR-DST, 7.0 +/- 0.7; BR-CsA, 9.2+/-3.1; CsA, 11.3 +/- 3.9 days). DOM-DST-CsA also did not affect graft survival (8.7 +/- 3.1 days). BR and CsA, similarly, had no effects in rats receiving a nonspecific transfusion (8.8 +/- 1.1 days). In contrast, BR administration in rats treated with DST and CsA unequivocally prolonged graft survival (17.0 +/- 1.4 days; P < 0.01 vs all controls), suggesting that hypoprolactinemia increased the tolerogenic effects of DST. Spleen and lymph node cells harvested from BR-DST-CsA rats on Postoperative Day 8 showed impaired responses to mitogenic or allogeneic challenges. Cytotoxic antibody levels at Day 5 were low in all groups receiving CsA. Possible mechanisms are discussed.
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PMID:Prolactin suppression enhances the effects of perioperative donor-specific blood transfusions on graft survival. 881 32

Male rats were grafted an anterior pituitary within breast muscles on day 5 or under the kidney capsule on day 30 or 60 of life. On the 70th day of life (rats operated on the 5th or 30th day) or on the 100th day of life (rats operated on the 60th day), rats were injected subcutaneously with Freund's complete adjuvant, being killed 2 days later. Rats that had received a pituitary graft on the 30th day showed a greater degree of hyper-prolactinemia than rats grafted on the 5th or 60th day. Analyzed as main factors in a factorial analysis of variance (ANOVA), pituitary transplants augmented splenic natural killer (NK) activity and lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced cell proliferation, and decreased splenic cell number. As indicated by significant interactions between treatment and age of transplantation in a factorial ANOVA, splenic NK activity augmented in rats grafted on the 30th day of life, while LPS and Con A splenic cell proliferation augmented in rats grafted neonatally. Spleen cellularity decreased after pituitary transplants in 30- and 60-day-old rats. In a second study, the effect of cyclosporine on spleen immune responses was tested by administering cyclosporine (5 mg/kg) or vehicle to rats grafted as in experiment 1 for 5 days before sacrifice. Cyclosporine decreased splenic NK activity and LPS- and Con A-induced cell proliferation regardless of the presence of a pituitary graft. In rats grafted on the 30th day of life, cyclosporine reversed the effect of pituitary grafts on splenic NK activity, and ectopic pituitary augmenting NK activity in vehicle-treated rats while decreasing it in cyclosporine-injected rats. Cyclosporine reversed the inhibitory effect of pituitary transplants on spleen cell number. The high circulating prolactin levels found in rats with pituitary grafts were decreased by cyclosporine administration. The results are compatible with age-dependent promoting and inhibitory effects of hyperprolactinemia on the immune responses of the spleen, which were antagonized by cyclosporine immunosuppression.
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PMID:Age-dependent effect of pituitary transplants on immune responses in rat spleen: modulatory effect of cyclosporine. 909 19

There is a concern that certain industrial chemicals found in the environment may mimic or antagonize endogenous hormones and adversely affect the endocrine as well as the immune system. The objective of this study was to determine if exposure of Crl:CD (SD)BR male rats to 17beta-estradiol (17beta-E2), an estrogen receptor agonist, or flutamide (FLUT), an androgen receptor antagonist, would significantly alter the primary IgM humoral immune response to sheep red blood cells (SRBC). This study was conducted in the context of a male in vivo Tier I battery designed to identify endocrine-active compounds (EACs). The Tier I male battery consists of organ weights coupled with a comprehensive hormonal assessment. Rats were dosed by the intraperitoneal route for 15 days with vehicle or 0.001, 0.0025, 0.0075, or 0.050 mg/kg/day 17beta-E2 or 0.25, 1, 5, or 20 mg/kg/day FLUT. Six days prior to termination, selected rats were injected intravenously with SRBC for assessment of humoral immune function. Spleen cell number and spleen and thymus weights were obtained. Serum was analyzed for anti-SRBC IgM antibody by using an enzyme-linked immunosorbent assay. At 0.050 mg/kg/day 17beta-E2, mean final body and absolute thymus weights were significantly decreased to 84 and 65% of control, respectively. 17beta-E2 did not significantly alter spleen weight, spleen cell number, or the primary IgM humoral immune response to SRBC. The no-observed-adverse-effect level (NOAEL) for immune system alteration was 0.050 mg/kg/day 17beta-E2 since the decrease in absolute thymus weight was judged to be secondary to the decrements in body weight. In the Tier I male battery, responses to 17beta-E2 included decreased absolute testis and epididymis weights, decreased relative accessory sex gland unit weights, hormonal alterations (decreased serum testosterone (T), dihydrotestosterone (DHT), and luteinizing hormone (LH), and increased serum prolactin and E2 levels). The lowest-observed-adverse-effect level (LOAEL) for the reproductive indices was 0.001 mg/kg/day 17beta-E2 based on the hormonal alterations seen at this level; no NOAEL was established. Exposure to FLUT did not significantly alter mean final body, spleen, or absolute thymus weights, spleen cell number, or the primary IgM humoral immune response to SRBC. A significant increase (118% of control) in relative thymus weight was observed at 20 mg/kg/day FLUT. The NOAEL for immune system alteration was 5 mg/kg/day FLUT based on the increased relative thymus weights that were judged to be compound-related. In the Tier I male battery, responses to FLUT included decreased absolute epididymis and relative accessory sex gland unit weights and hormonal alterations (increased serum T, DHT, E2, and LH, and decreased follicle stimulating hormone levels). The LOAEL for the reproductive indices was 0.25 mg/kg/day FLUT based on the hormonal alterations seen at this level; no NOAEL was established. Based on these data, the reproductive and not the immune system appears to be the primary target organ of toxicity in young adult male rats treated with either 17beta-E2 or FLUT.
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PMID:Evaluation of the primary humoral immune response following exposure of male rats to 17beta-estradiol or flutamide for 15 days. 992 70

In the present study, we investigated the time-dependent interactive effects of daily injections of prolactin (PRL) and corticosterone (CORT) on the activation of lymphocyte function and inhibition of tumor growth in vivo in mice. BALB/c mice were injected subcutaneously with EMT-6 fibrosarcoma cells (a murine connective tissue tumor cell derived from mammary gland), and then different groups of animals were treated with PRL (1 microg/g body weight [BW] ip) at Oh, 4h, 8h, 12h, 16h, or 20h after CRT (1 microg/g BW ip) daily for 10 days. Different control groups were vehicle treated or treated with either hormone alone. Mice were kept in constant light 1 week before and during injections and in a 14:10 light-dark cycle thereafter. Tumor progression was monitored for up to 21 days after the cessation of treatment, and thereafter spleen lymphocytes were harvested and tested for mitogen-triggered proliferation. Prolactin administration at 8h or 16-20h after corticosteroid treatment reduced tumor volume by 77% and 49%, respectively, relative to vehicle-treated controls. Other time relations of hormone treatment were ineffectual. Further studies indicated that the immunosuppressant cyclosporin A (CSA) substantially stimulated tumor growth; this effect was completely abrogated by a simultaneous 8h related hormone treatment. How ever, the 8h hormone treatment was ineffective in inhibiting tumor growth in T-cell-deficient nude mice. Spleen lymphocytes from tumor-bearing (TB) mice showed an elevated basal proliferative capacity stimulated by concanavalin A (ConA; a stimulus for T-cell proliferation) and lipopolysaccharide (LPS; a stimulus for B-cell proliferation) compared to non-TB mice. Spleen lymphocytes from TB mice treated with CORT and PRL at 8h intervals exhibited an increased spontaneous (as well as LPS- and ConA- triggered) proliferation (by 104%, 48%, and 70%, respectively) compared with vehicle control TB mice. Fluorescence-activated cell sorting (FACS) analysis of splenocytes from hormone-treated animals indicated a 34-100% increase in the CD4+ (e.g., T helper cell) population. Treatment of animals with either hormone alone did not inhibit tumor growth or stimulate immune function relative to vehicle controls. The daily rhythms of plasma PRL, CORT, and thyroxine were all substantially altered by the presence of tumor in these mice. These results indicate that appropriately timed daily treatment of PRL and CORT can attenuate tumor growth, in part, via activation of antitumor immune mechanisms. Collectively, these data suggest that circadian neuroendocrine activities must be temporally organized appropriately to inhibit tumor growth.
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PMID:Timed daily administration of prolactin and corticosteroid hormone reduces murine tumor growth and enhances immune reactivity. 1037 1

Previously, the hormone prolactin (PRL) has been found to protect against development of type 1 diabetes induced by multiple injections of streptozotocin (STZ) in mice. To further investigate this effect of PRL, C57BL/Ks mice were injected intraperitoneally with STZ (40 mg/kg body weight) or NaCl for 5 days and PRL (4 mg/kg body weight) or NaCl for 14 days. On day 15, splenocytes were isolated from the in vivo treated mice. Spleen cell preparations depleted in erythrocytes and macrophages were stained for cytoplasmic TNF-alpha, IFN-gamma and IL-10 and analyzed with flow cytometry. Isolated spleen cells were also cultured (RPMI 1640+10% fetal bovine serum) for 24 h. Thereafter, cytokine mRNA expression by the spleen cells was measured by real-time PCR and cytokine secretion determined by enzyme linked immunosorbent assay (ELISA). Freshly isolated spleen cell preparations from PRL and STZ+PRL treated animals seemed to have an increased frequency of IL-10 positive cells compared to controls. In cultured spleen cells isolated from STZ treated mice, IFN-gamma and IL-10 mRNA expression was up-regulated. PRL treatment down-regulated the mRNA expression of these cytokines and also TNF-alpha in the splenocytes obtained from animals treated with STZ. The accumulation of these cytokines in the cultures of the explanted splenocytes showed only minor differences between the experimental groups. Overall, the data seems to favor the view that PRL enhanced a Th2 response, which may reflect the preventive effect of PRL against development of multiple low dose STZ diabetes in mice.
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PMID:Prolactin regulation of the expression of TNF-alpha, IFN-gamma and IL-10 by splenocytes in murine multiple low dose streptozotocin diabetes. 1605 32