EP24.15 as a Potential Regulator of Kisspeptin Within the Neuroendocrine Hypothalamus.

Abstract:

:The neuropeptide kisspeptin (Kiss1) is integral to the advent of puberty and the generation of cyclical LH surges. Although many complex actions of Kiss1 are known, the mechanisms governing the processing/regulation of this peptide have not been unveiled. The metallo enzyme, endopeptidase 24.15 (thimet oligopeptidase), has been demonstrated to play a key role in the processing and thus the duration of action of the reproductive neuropeptide, GnRH, which signals downstream of Kiss1. Initial in silico modeling implied that Kiss1 could also be a putative substrate for EP24.15. Coincubation of Kiss1 and EP24.15 demonstrated multiple cleavages of the peptide predominantly between Arg29-Gly30 and Ser47-Phe48 (corresponding to Ser5-Phe6 in Kiss-10; Kiss-10 as a substrate had an additional cleavage between Phe6-Gly7) as determined by mass spectrometry. Vmax for the reaction was 2.37±0.09 pmol/min · ng with a Km of 19.68 ± 2.53μM, which is comparable with other known substrates of EP24.15. EP24.15 immunoreactivity, as previously demonstrated, is distributed in cell bodies, nuclei, and processes throughout the hypothalamus. Kiss1 immunoreactivity is localized primarily to cell bodies and fibers within the mediobasal and anteroventral-periventricular hypothalamus. Double-label immunohistochemistry indicated coexpression of EP24.15 and Kiss1, implicating that the regulation of Kiss1 by EP24.15 could occur in vivo. Further studies will be directed at determining the precise temporal sequence of EP24.15 effects on Kiss1 as it relates to the control of reproductive hormone secretion and treatment of fertility issues.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Woitowich NC,Philibert KD,Leitermann RJ,Wungjiranirun M,Urban JH,Glucksman MJ

doi

10.1210/en.2015-1580

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

820-30

issue

2

eissn

0013-7227

issn

1945-7170

journal_volume

157

pub_type

杂志文章
  • The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones.

    abstract::It has previously only been possible to assess osteoclastic bone resorption in intact bone, where other cell types may modify or mediate osteoclastic responses to environmental agents. We have recently developed techniques which enable us to measure bone resorption by osteoclasts extracted from bone and have used thes...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-116-1-234

    authors: Chambers TJ,McSheehy PM,Thomson BM,Fuller K

    更新日期:1985-01-01 00:00:00

  • Immediate-early transcriptional response to angiotensin II in human adrenocortical cells.

    abstract::Angiotensin II binds to the angiotensin II receptors type 1 (AT1 receptors) in adrenocortical cells and triggers an intracellular signaling cascade leading to changes in the gene expression pattern. Here, we show that stimulation with angiotensin II induces the expression of biologically active early growth response (...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2011-1243

    authors: Thiel G,Rössler OG

    更新日期:2011-11-01 00:00:00

  • Arginine vasopressin triggers intracellular calcium release, a calcium-activated potassium current and exocytosis in identified rat corticotropes.

    abstract::Arginine vasopressin (AVP) stimulates the secretion of ACTH from pituitary corticotropes. We investigated the action of AVP in single corticotropes of male rats. Corticotropes were identified with the reverse hemolytic plaque assay using antibodies against ACTH. Using the whole-cell recording technique in conjunction ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.5.5999

    authors: Tse A,Lee AK

    更新日期:1998-05-01 00:00:00

  • Neurons that migrate from the olfactory epithelium in the chick express luteinizing hormone-releasing hormone.

    abstract::In several mammalian species, luteinizing hormone-releasing hormone (LHRH) neurons have been shown to migrate from nasal regions to the brain during early development. Using immunocytochemistry, we have identified LHRH containing neurons in developing chick embryos. In embryonic day 4 (E4) and E5 animals, a small grou...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-128-3-1676

    authors: Norgren RB Jr,Lehman MN

    更新日期:1991-03-01 00:00:00

  • Developmental regulation of the sodium/hydrogen ion exchangers and their regulatory factors in baboon placental syncytiotrophoblast.

    abstract::Although Na+/H+ exchange is important to maintenance of pH and volume and thus placental-fetal homeostasis, regulation of the Na+/H+ exchange system is incompletely understood. We previously showed that Na+/H+ exchanger (NHE)1 and -3 and their regulatory factors NHERF1 and -2 were expressed in human and nonhuman prima...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-0887

    authors: Pepe GJ,Burch MG,Albrecht ED

    更新日期:2006-06-01 00:00:00

  • The chronic intracerebroventricular infusion of interleukin-1 beta alters the activity of the hypothalamic-pituitary-gonadal axis of cycling rats. I. Effect on LHRH and gonadotropin biosynthesis and secretion.

    abstract::We have previously reported that the acute injection of interleukin-1 beta (IL-1 beta) into the brain ventricles of intact female rats promptly decreases LHRH release and inhibits gene expression of this peptide in the medial preoptic area (MPOA). The present studies were therefore designed to determine whether contin...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.133.6.8243260

    authors: Rivest S,Lee S,Attardi B,Rivier C

    更新日期:1993-12-01 00:00:00

  • Studies on the irreversible nature of prolactin binding to receptors.

    abstract::Studies on hormone-receptor interactions generally assume that the formation of a hormone-receptor complex is a reversible process. This assumption has been examined directly in three experiments using liver membrane receptor preparations from pregnant rats and ovine PRL (oPRL). In Exp 1, Receptors were preincubated w...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-106-1-402

    authors: van der Gugten AA,Waters MJ,Murthy GS,Friesen HG

    更新日期:1980-01-01 00:00:00

  • Chemical UV Filters Mimic the Effect of Progesterone on Ca2+ Signaling in Human Sperm Cells.

    abstract::Progesterone released by cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the cationic channel of sperm (CatSper) Ca2+ channel and controls multiple Ca2+-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of pro...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2016-1473

    authors: Rehfeld A,Dissing S,Skakkebæk NE

    更新日期:2016-11-01 00:00:00

  • Characterization, neurosteroid binding and brain distribution of human membrane progesterone receptors δ and {epsilon} (mPRδ and mPR{epsilon}) and mPRδ involvement in neurosteroid inhibition of apoptosis.

    abstract::Three members of the progestin and adipoQ receptor (PAQR) family, PAQR-7, PAQR-8, and PAQR-5 [membrane progesterone (P4) receptor (PR) (mPR)α, mPRβ, and mPRγ], function as plasma mPRs coupled to G proteins in mammalian cells, but the characteristics of two other members, PAQR6 and PAQR9 (mPRδ and mPRε), remain unclear...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2012-1772

    authors: Pang Y,Dong J,Thomas P

    更新日期:2013-01-01 00:00:00

  • Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut.

    abstract::The ileal proglucagon-derived peptides (PGDPs) play important roles in the regulation of gastric function and insulin secretion. We have previously demonstrated the existence of a proximal-distal enteroendocrine loop mediated by glucose-dependent insulinotropic peptide (GIP), through which intestinal PGDP secretion is...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.137.6.8641190

    authors: Roberge JN,Gronau KA,Brubaker PL

    更新日期:1996-06-01 00:00:00

  • Processing of human growth hormone by rat hepatocytes in monolayer culture.

    abstract::The fate of cell-bound [125I]iodo-human GH ([125I]iodo-hGH) was studied in monolayer cultures of hepatocytes from pregnant and nonpregnant rats. Both the binding of [125I]iodo-hGH and its degradation were significantly higher in cells from pregnant than from nonpregnant rats. The positive correlation between the numbe...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-114-5-1475

    authors: Wakai K,Tsushima T,Isozaki O,Sato Y,Sato K,Shizume K

    更新日期:1984-05-01 00:00:00

  • Production of insulin-like growth factors, platelet-derived growth factor, and transforming growth factors and their role in the density-dependent growth regulation of a differentiated embryonal carcinoma cell line.

    abstract::P19 EPI-7, a differentiated murine embryonal carcinoma cell line with an epithelioid morphology, does not require external growth factors for proliferation under clonal and subconfluent conditions. At saturation density, however, cells become quiescent in the G1/G0 phase of the cell cycle from which they can be restim...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-124-4-2029

    authors: van Zoelen EJ,Koornneef I,Holthuis JC,Ward-van Oostwaard TM,Feijen A,de Poorter TL,Mummery CL,van Buul-Offers SC

    更新日期:1989-04-01 00:00:00

  • Hormonal regulation of rabbit uteroglobin gene transcription.

    abstract::Synthesis of uteroglobin in rabbit uterine epithelial cells during early pregnancy is induced by progesterone and apparently suppressed by estrogen. To assess whether the steroid hormones exert regulatory effects on the expression of the uteroglobin gene, we performed transcriptional rate assays in endometrial nuclei ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-112-3-871

    authors: Shen XZ,Tsai MJ,Bullock DW,Woo SL

    更新日期:1983-03-01 00:00:00

  • Biphasic effects of transforming growth factor-beta on the production of osteoclast-like cells in mouse bone marrow cultures: the role of prostaglandins in the generation of these cells.

    abstract::Osteoclast-like multinucleated giant cells are induced in bone marrow cultures by 1,25-dihydroxyvitamin D3 and other agents. These cells resemble osteoclasts in their morphology, their ability to resorb bone, and the possession of calcitonin receptors. We report here a biphasic effect of transforming growth factor-bet...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-126-6-3153

    authors: Shinar DM,Rodan GA

    更新日期:1990-06-01 00:00:00

  • Altered bcl-2 and bax expression and intracellular Ca2+ signaling in apoptosis of pancreatic cells and the impairment of glucose-induced insulin secretion.

    abstract::Apoptosis is the process of cellular self-destruction, and genes such as bcl-2 and bax are known to inhibit and promote apoptosis, respectively. In this study, we show that apoptosis can be induced in pancreatic beta-cell lines, and we investigate the apoptotic pathways through the bcl-2 and bax genes and intracellula...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.3.5798

    authors: Mizuno N,Yoshitomi H,Ishida H,Kuromi H,Kawaki J,Seino Y,Seino S

    更新日期:1998-03-01 00:00:00

  • Cnr2 deficiency confers resistance to inflammation-induced preterm birth in mice.

    abstract::Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate immune responses. We ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2014-1387

    authors: Sun X,Cappelletti M,Li Y,Karp CL,Divanovic S,Dey SK

    更新日期:2014-10-01 00:00:00

  • Importance of uterine cell death, renewal, and their hormonal regulation in hamsters that show progesterone-dependent implantation.

    abstract::This study was initiated to investigate the significance of uterine cell death and proliferation during the estrous cycle and early pregnancy and their correlation with sex steroids in hamsters where blastocyst implantation occurs in only progesterone-primed uteri. The results obtained in hamsters were also compared w...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2005-1555

    authors: Zhang Q,Paria BC

    更新日期:2006-05-01 00:00:00

  • Effects of electrical stimulation of the medial basal hypothalamus on the in vivo release of luteinizing hormone-releasing hormone in the prepubertal and peripubertal female monkey.

    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

    authors: Claypool LE,Watanabe G,Terasawa E

    更新日期:1990-12-01 00:00:00

  • sFlt-1 gene therapy of follicular thyroid carcinoma.

    abstract::Tumor progression largely depends on blood supply and neovessel formation, and angiogenesis is emerging as a promising target for cancer therapy. Vascular endothelial growth factor (VEGF), a major proangiogenic molecule, stimulates angiogenesis via promoting endothelial proliferation, survival and migration. VEGF has ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2003-1106

    authors: Ye C,Feng C,Wang S,Wang KZ,Huang N,Liu X,Lin Y,Li M

    更新日期:2004-02-01 00:00:00

  • Lysophosphatidic acid inhibits C-type natriuretic peptide activation of guanylyl cyclase-B.

    abstract::C-type natriuretic peptide (CNP), found in endothelial cells, chondrocytes, and neurons, binds its cognate transmembrane receptor, natriuretic peptide receptor-B (NPR-B/GC-B), and stimulates the synthesis of the intracellular signaling molecule, cGMP. The known physiologic consequences of this binding event are vasore...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2002-220702

    authors: Abbey SE,Potter LR

    更新日期:2003-01-01 00:00:00

  • Adrenocorticotropin increases expression of c-fos and beta-actin genes in the rat adrenals.

    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

    authors: Imai T,Seo H,Murata Y,Ohno M,Satoh Y,Funahashi H,Takagi H,Matsui N

    更新日期:1990-10-01 00:00:00

  • Effect of zinc deficiency on serum somatomedin levels and skeletal growth in young rats.

    abstract::We have studied potential mechanisms by which zinc deficiency (ZD) may result in growth impairment in young animals. Dietary-induced ZD in young rats resulted in diminished skeletal growth as measured by tibial epiphyseal width. Treatment with bovine GH (bGH) did not increase skeletal growth suggesting GH resistance r...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-114-5-1860

    authors: Oner G,Bhaumick B,Bala RM

    更新日期:1984-05-01 00:00:00

  • Effects of Peripheral Neurotensin on Appetite Regulation and Its Role in Gastric Bypass Surgery.

    abstract::Neurotensin (NT) is a peptide expressed in the brain and in the gastrointestinal tract. Brain NT inhibits food intake, but the effects of peripheral NT are less investigated. In this study, peripheral NT decreased food intake in both mice and rats, which was abolished by a NT antagonist. Using c-Fos immunohistochemist...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2016-1329

    authors: Ratner C,Skov LJ,Raida Z,Bächler T,Bellmann-Sickert K,Le Foll C,Sivertsen B,Dalbøge LS,Hartmann B,Beck-Sickinger AG,Madsen AN,Jelsing J,Holst JJ,Lutz TA,Andrews ZB,Holst B

    更新日期:2016-09-01 00:00:00

  • Epigenomic silencing of the BMP-4 gene in pituitary adenomas: a potential target for epidrug-induced re-expression.

    abstract::Bone morphogenetic protein (BMP)-4 is a key mediator of anterior pituitary organogenesis. However, through inappropriate expression patterns, BMP-4 is also pathogenic in a pituitary adenoma subtype-specific context. In these cases, increase or decrease in BMP-4 in lactotroph- and corticotroph-derived adenomas, respect...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/en.2012-1231

    authors: Yacqub-Usman K,Duong CV,Clayton RN,Farrell WE

    更新日期:2012-08-01 00:00:00

  • S14: insights from knockout mice.

    abstract::Spot 14 (S14) is a protein whose mRNA is rapidly up-regulated by lipogenic stimuli including thyroid hormone and a high-carbohydrate diet. Previous investigation into the role of S14 suggested that it is involved in de novo lipogenesis. Knockout of the gene in mice has given further support to this hypothesis. The lac...

    journal_title:Endocrinology

    pub_type: 杂志文章,评审

    doi:10.1210/en.2006-0473

    authors: LaFave LT,Augustin LB,Mariash CN

    更新日期:2006-09-01 00:00:00

  • 1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent.

    abstract::We and others have recently shown that 1alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibits cell proliferation and increases secretion of prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human prostate cancer cell line. The present study was designed to investigate the possible int...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.138.8.5328

    authors: Zhao XY,Ly LH,Peehl DM,Feldman D

    更新日期:1997-08-01 00:00:00

  • Developmental and tissue-specific regulation of proglucagon gene expression.

    abstract::The pattern of glucagon gene expression and the posttranslational processing of proglucagon was studied in the fetal and neonatal rat. Pancreatic immunoreactive glucagon (IRG) and glucagon-like immunoreactivity (GLI) were low in both fetal pancreas and intestine, respectively. Immediately after birth, pancreatic IRG r...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo-127-5-2217

    authors: Lee YC,Brubaker PL,Drucker DJ

    更新日期:1990-11-01 00:00:00

  • Endotoxin injection increases growth hormone and somatostatin secretion in sheep.

    abstract::Endotoxin has been shown to stimulate GH secretion in human and sheep. However, changes in hypothalamic neurohormones involved in the GH regulation by endotoxin have never been studied in vivo. In sheep it is possible to collect hypophysial portal blood (HPB) and quantify GH-releasing hormone (GHRH) and somatostatin (...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.139.6.6072

    authors: Briard N,Guillaume V,Frachebois C,Rico-Gomez M,Sauze N,Oliver C,Dutour A

    更新日期:1998-06-01 00:00:00

  • Targeting of green fluorescent protein to secretory granules in oxytocin magnocellular neurons and its secretion from neurohypophysial nerve terminals in transgenic mice.

    abstract::Oxytocin (OT) is a hypothalamic nonapeptide that is synthesized as part of a larger precursor protein that also contains an approximately 10-kDa protein called neurophysin at its C-terminus. This precursor protein is trafficked through the regulated secretory pathway into secretory granules and then axonally transport...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.143.3.8700

    authors: Zhang BJ,Kusano K,Zerfas P,Iacangelo A,Young WS 3rd,Gainer H

    更新日期:2002-03-01 00:00:00

  • Differential activation of the IGF binding protein-3 promoter by butyrate in prostate cancer cells.

    abstract::Sodium butyrate (NaB), a dietary micronutrient, is a potent growth inhibitor that initiates cell differentiation in many cell types, including prostate cancer cells. The molecular mechanisms by which these effects occur remain largely unknown. In this study, we investigated the effects of NaB on the expression of IGF ...

    journal_title:Endocrinology

    pub_type: 杂志文章

    doi:10.1210/endo.143.5.8766

    authors: Tsubaki J,Hwa V,Twigg SM,Rosenfeld RG

    更新日期:2002-05-01 00:00:00