Abstract:
:The ABCB1-type multidrug resistance efflux transporter P-glycoprotein (P-gp) has been hypothesized to regulate hypothalamic-pituitary-adrenal axis activity by limiting the access of glucocorticoids to the brain. In vivo systemic administration studies using P-gp-deficient mice have shown increased glucocorticoid entry to the brain compared with wild-type controls. However, these studies did not control for the presence of radiolabeled drug in the capillaries, verify an intact blood-brain barrier, or confirm stability of the glucocorticoids used. In the present study, an in situ brain perfusion method, coupled with capillary depletion and HPLC analyses, was used to quantify brain uptake of [3H]dexa-methasone, [3H]cortisol, and [3H]corticosterone in P-gp-deficient and control mice. A vascular marker was included in these experiments. The results show that brain uptake of [3H]dexamethasone was increased in the frontal cortex, hippocampus, hypothalamus, and cerebellum of P-gp-deficient mice compared with wild-type controls. Brain uptake of [3H]cortisol was increased in the hypothalamus of P-gp-deficient mice compared with wild-type controls, but no differences were detected in other regions. Brain uptake of [3H]corticosterone was not increased in P-gp-deficient mice compared with wild-type controls in any brain areas. After our systemic administration of the same radiolabeled glucocorticoids, HPLC analysis of plasma samples identified additional radiolabeled components, likely to be metabolites. This could explain previous findings from systemic administration studies, showing an effect of P-gp not only for dexamethasone and cortisol, but also for corticosterone. This in situ study highlights the different affinities of dexamethasone, cortisol, and corticosterone for P-gp, and suggests that the entry of the endogenous glucocorticoids into the mouse brain is not tightly regulated by P-gp. Therefore, our current understanding of the role of P-gp in hypothalamic-pituitary-adrenal regulation in mice requires revision.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Mason BL,Pariante CM,Thomas SAdoi
10.1210/en.2008-0041subject
Has Abstractpub_date
2008-10-01 00:00:00pages
5244-53issue
10eissn
0013-7227issn
1945-7170pii
en.2008-0041journal_volume
149pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::The assembly of the developmentally arrested primordial follicle and the subsequent transition of the primordial follicle to the primary follicle are critical processes in normal ovarian physiology that remain to be elucidated. Ovarian follicles do not proliferate and the primordial follicles present in the neonate re...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2002-0131
更新日期:2003-08-01 00:00:00
abstract::The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a-->g missense mutation in exon 5 of the GH gene, which translates to a D167G amino acid exchange in the mature protein. Mice carrying the mutation are characterized by dwarfism, predominantly due to the reduction (sma1/+) or absen...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-1125
更新日期:2004-05-01 00:00:00
abstract::In this study the hypothesis that the LHRH neurosecretory system of the prepubertal female monkey has the capacity to function in a manner comparable to that of monkeys in more mature stages of development was tested. Using push-pull perfusion in the stalk-median eminence, effects of electrical stimulation of the medi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-6-3014
更新日期:1990-12-01 00:00:00
abstract::Animals shipped from commercial suppliers to laboratories are exposed to a wide variety of stressors. Female C57Bl6/J mice shipped during the peripubertal/adolescent period (6 wk old) display lower levels of female sexual behavior in response to estradiol and progesterone injections after ovariectomy when tested in ad...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-1595
更新日期:2009-05-01 00:00:00
abstract::An isolated perfused rabbit ovary preparation was used to determine the effects of cyanoketone, a potent inhibitor of 3 beta-hydroxysteroid dehydrogenase, on ovulation, ovum maturation and fertilizability, and steroid production. In the first experiment, cyanoketone (10(-4) M) was added to the perfusate of one ovary. ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-6-2555
更新日期:1987-06-01 00:00:00
abstract::Insulin secretion by beta-cells of pancreatic islets is regulated by various soluble factors including glucose and hormones. The importance of direct cell-cell communication among beta-cells or between beta-cells and other cell types for such regulation has remained unclear, however. Transmembrane proteins Src homolog...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0236
更新日期:2008-11-01 00:00:00
abstract::The formation of junctional complexes between adjacent epithelial principal cells leads to formation of the blood-epididymal barrier; this barrier is complete by 21 days of postnatal age. Cadherins are cell surface proteins that mediate intercellular adhesion and are involved in the formation of adherence, gap, and ti...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.132.3.7679970
更新日期:1993-03-01 00:00:00
abstract::We previously showed that receptor-like protein tyrosine phosphatase (RPTP)-alpha inhibited insulin-increased prolactin gene transcription. Others suggested that RPTPalpha was a key intermediary between integrins and activation of Src. We present evidence that inhibition of insulin-increased prolactin gene transcripti...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1386
更新日期:2005-08-01 00:00:00
abstract::The occurrence of the thyroid hormone-binding plasma protein transthyretin in the bloodstream was investigated for four American marsupial species. Serum samples were analyzed by incubation with radioactive T4, followed by electrophoresis, then autoradiography, and Western blotting. Transthyretin was found in serum fr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.8.8754780
更新日期:1996-08-01 00:00:00
abstract::It is established that androgens and unidentified Sertoli cell (SC)-derived factors can influence the development of adult Leydig cells (LC) in rodents, but the mechanisms are unclear. We evaluated adult LC development and function in SC-selective androgen receptor (AR) knockout (SCARKO) and complete AR knockout (ARKO...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0300
更新日期:2005-09-01 00:00:00
abstract::The multifunctional cytokine tumor necrosis factor-alpha (TNF alpha) stimulates osteoclastic resorption. It is not known which steps in osteoclast formation are affected by TNF alpha. We have investigated the effects of recombinant human TNF alpha (rhTNF alpha) on osteoclast development and osteoclastic resorption in ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-3-1596
更新日期:1991-09-01 00:00:00
abstract::A healthy nutritional state is required for all aspects of reproduction and is signaled by the adipokine leptin. Leptin acts in a relatively narrow concentration range: too much or too little will compromise fertility. The leptin signal timing is important to prepubertal development in both sexes. In the brain, leptin...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa204
更新日期:2021-02-01 00:00:00
abstract::The purpose of the present study was to further examine the hypothesis that activation of G protein-coupled receptor 54 (GPR54) signaling at the end of the juvenile phase of primate development is responsible for initiation of gonadarche and the onset of puberty. Accordingly, we determined whether repetitive iv admini...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-1261
更新日期:2006-02-01 00:00:00
abstract::Serum and pituitary thyroid-stimulating hormone (TSH) was measured by radioimmunoassay in male and female Sprague-Dawley rats from 21 through 80 days of age. In males, serum TSH levels increased progressively from days 30 through 50, and were found to be lower on days 60, 70, and 80. In females, serum TSH levels were ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-6-1365
更新日期:1976-06-01 00:00:00
abstract::In order to elucidate the putative role of inhibin in regulation of spermatogenesis, expression of inhibin subunits was examined at defined stages of the cycle of the rat seminiferous epithelium. Twenty 2-mm segments of seminiferous tubules at stages XIII-I, II-VI, VII-VIII, and IX-XII were dissected using the transil...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-2-987
更新日期:1989-02-01 00:00:00
abstract::The uptake of [125I]triiodothyroacetic acid ([125I]Triac) in anterior pituitary cells was investigated and compared with that of [125I]T3. Furthermore, the effects of Triac, T3, and T4 on TSH release were compared. Cells isolated from adult male Wistar rats were cultured for 3 days in medium with 10% fetal calf serum....
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.6.7988460
更新日期:1994-12-01 00:00:00
abstract::Open pig thyroid follicles in which the apical surface of the follicle cells is in direct contact with the incubation medium were used to study the effect of stimulated exocytosis and stimulated H2O2 generation on the iodination of protein in the incubation medium. In previous studies on this system of follicles we ha...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-2-488
更新日期:1988-02-01 00:00:00
abstract::We studied the direct effects of glucocorticoids on plasminogen activator (PA) production by rat granulosa cells. PA production was assayed by culturing rat granulosa cells on [125I]fibrin plates and determining the extent of fibrinolysis after addition of the specific substrate plasminogen. In granulosa cells from pr...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-4-1595
更新日期:1989-04-01 00:00:00
abstract::Insulin stimulation of glucose transport involves the translocation of vesicles containing the glucose transporter Glut 4 to the plasma membrane. Since low mol wt GTP-binding proteins (LMW-GTP-binding proteins) have been implicated in the regulation of vesicular trafficking, we have analyzed these proteins in adipocyt...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-129-6-3343
更新日期:1991-12-01 00:00:00
abstract::Japanese quail, a species with a precocial pattern of development, were used as a model for studying the ontogeny of thyroid responses to TSH. Thiourea was administered to embryos early in incubation, and the effects were assessed by measuring thyroid 32P uptake, serum thyroid hormones, thyroid weights, and body weigh...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-114-4-1238
更新日期:1984-04-01 00:00:00
abstract::The anterior pituitary (AP) is made of five different cell types. The relative abundance and phenotype of AP cells may change in different physiological situations as an expression of pituitary plasticity. Here, we analyze in detail the phenotype of mouse corticotropes and the effects of acute cold stress on AP cell p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-1030
更新日期:2008-05-01 00:00:00
abstract::Recent evidence suggests that ANF neurons of the hypothalamus are dopamine sensitive, and the catecholamine may exert a direct stimulatory or inhibitory effect on the neurons mediated through D1 or D2 receptors, respectively, in a manner related to the differential dopamine binding sensitivity of the two receptor subt...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.12.7588310
更新日期:1995-12-01 00:00:00
abstract::The purpose of these experiments was to test the hypothesis that estrogen has an anabolic effect on cancellous bone formation in long bones of growing rats. In the present studies, estrogen decreased measurements related to cancellous bone formation, including osteoblast number, fluorochrome-labeled bone perimeter, an...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.6.8243320
更新日期:1993-12-01 00:00:00
abstract::Serum levels of progesterone in hysterectomized gilts were determined to evaluate the effects of exogenous 17 beta-estradiol (17 beta-E2) on the secretory activity of aging corpora lutea. Gilts were hysterectomized on day 6 of the estrous cycle and given im injections of 17 beta-E2 to mimic blood levels of endogenous ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-5-1876
更新日期:1984-11-01 00:00:00
abstract::A myometrial explant culture system was developed to investigate the effect of progesterone and the antiprogestagen RU486 on prostacyclin (PGI2) and thromboxane A2 (TXA2) synthesis by the rat myometrium. After culture, eicosanoid synthesis was stimulated with arachidonic acid (AA) and the calcium ionophore A23187 (A23...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-119-2-655
更新日期:1986-08-01 00:00:00
abstract::An estrogen-responsive uterine proenzyme of a proteinase in the immature rat uterus has been known for some time. Its mol wt is 77,000, its N-terminal amino acid sequence is the same as prothrombin's for 15 residues, it contains gamma-carboxyl glutamate residues, its biosynthesis is prevented by warfarin, it cross-rea...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-1-167
更新日期:1990-01-01 00:00:00
abstract::Humanin is a peptide that is cytoprotective against stresses in many cell types. We investigated whether a potent humanin analogue S14G-humanin (HNG) would protect against chemotherapy-induced damage to normal cells without interfering with the chemotherapy-induced suppression of cancer cells. Young adult male mice we...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2015-1542
更新日期:2015-12-01 00:00:00
abstract::Exposure to environmental toxicants during fetal development alters gene expression and promotes disease later in life. Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used for the manufacturing of consumer products. Exposure to DEHP has been associated with obesity, asthma, and low T levels. In utero expos...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2014-1436
更新日期:2015-01-01 00:00:00
abstract::It is widely accepted that expression of protooncogenes is coupled with cellular proliferation and differentiation. Since ACTH stimulates not only steroidogenesis but also cellular proliferation, we investigated whether ACTH affects the expression of c-fos, c-myc, and beta-actin genes. The effect of ACTH on adrenal gl...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-4-1742
更新日期:1990-10-01 00:00:00
abstract::To better understand the role of peptide growth factors in sex steroid hormone-mediated growth of the female reproductive tract, the effect of estrogen on the expression of transforming growth factor-alpha (TGF alpha) in mouse uterus was investigated. Our results show that estrogen induces the expression of TGF alpha ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.4.1396310
更新日期:1992-10-01 00:00:00