scholarly journals Dynamic Regulation of Mouse Ovarian Stanniocalcin Expression during Gestation and Lactation*

Endocrinology ◽  
2000 ◽  
Vol 141 (9) ◽  
pp. 3412-3421 ◽  
Author(s):  
Harminder K. Deol ◽  
Robin Varghese ◽  
Graham F. Wagner ◽  
Gabriel E. DiMattia
Keyword(s):  
Gene Expression ◽  
Postnatal Development ◽  
Messenger Rna ◽  
Protein Localization ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Glycoprotein Hormone ◽  
Dynamic Regulation ◽  
Functional Relationships ◽  
Mammalian Tissues

Abstract Stanniocalcin is a glycoprotein hormone that appears to play a paracine/autocrine role in several mammalian tissues. Recently studies have shown that stanniocalcin is highly expressed in the ovaries of mice and humans and we have investigated its expression in the mouse ovary during several physiological states to identify potential functional relationships. During postnatal development the pattern of stanniocalcin (STC) gene expression begins to become thecal-restricted as early as day 5 and achieves the adult pattern of expression by two weeks of age. During postnatal development the primary sites of STC protein localization are the theca and oocytes and after maturation it is also strongly concentrated in the corpora lutea. Over the estrous cycle the pattern of both STC gene expression and protein localization do not show dramatic changes though STC immunoreactivity (STCir) staining appears to be greatest during metestrus I. In the superovulation model, however, we observed a significant increase in STC messenger RNA (mRNA) levels after treatment with hCG implying regulation by LH. During gestation the expression of ovarian STC increases 15-fold and is localized to the theca-interstitial cells with lower expression also being found in the corpora lutea. STC also becomes detectable in the serum for the first time suggesting an endocrine role for STC during gestation. Interestingly, the presence of a nursing litter appears to up-regulate STC gene expression in lactating mice suggesting a role for ovarian STC in lactation. Also striking is the intense STCir staining found in oocytes as they are devoid of STC mRNA, thus implying a role for STC in oocyte maturation. Stanniocalcin, to our knowledge, is unique because no other secreted proteins produced by the ovarian thecal-interstitial compartment are significantly induced during mouse pregnancy. In summary, our data provide evidence for the active regulation of STC expression in the ovary during gestation and lactation and therefore implies that STC is a new regulator of the gestational and nursing state.

scholarly journals Differential Effects of Gonadotropin-Releasing Hormone (GnRH) Pulse Frequency on Gonadotropin Subunit and GnRH Receptor Messenger Ribonucleic Acid Levels in Vitro*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1224-1231 ◽  
Author(s):  
Ursula B. Kaiser ◽  
Andrzej Jakubowiak ◽  
Anna Steinberger ◽  
William W. Chin
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Pulse Frequency ◽  
Gnrh Receptor ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Subunit Gene ◽  
Differential Effects ◽  
Messenger Ribonucleic Acid

Abstract The hypothalamic hormone, GnRH, is released and transported to the anterior pituitary in a pulsatile manner, where it binds to specific high-affinity receptors and regulates gonadotropin biosynthesis and secretion. The frequency of GnRH pulses changes under various physiological conditions, and varying GnRH pulse frequencies have been shown to regulate differentially the secretion of LH and FSH and the expression of the gonadotropin α, LHβ, and FSHβ subunit genes in vivo. We demonstrate differential effects of varying GnRH pulse frequency in vitro in superfused primary monolayer cultures of rat pituitary cells. Cells were treated with 10 nm GnRH pulses for 24 h at a frequency of every 0.5, 1, 2, or 4 h. α, LHβ, and FSHβ messenger RNA (mRNA) levels were increased by GnRH at all pulse frequencies. α and LHβ mRNA levels and LH secretion were stimulated to the greatest extent at a GnRH pulse frequency of every 30 min, whereas FSHβ mRNA levels and FSH secretion were stimulated maximally at a lower GnRH pulse frequency, every 2 h. GnRH receptor (GnRHR) mRNA levels also were increased by GnRH at all pulse frequencies and were stimulated maximally at a GnRH pulse frequency of every 30 min. Similar results were obtained when the dose of each pulse of GnRH was adjusted to maintain a constant total cumulative dose of GnRH over 24 h. These data show that gonadotropin subunit gene expression is regulated differentially by varying GnRH pulse frequencies in vitro, suggesting that the differential effects of varying GnRH pulse frequencies on gonadotropin subunit gene expression occur directly at the level of the pituitary. The pattern of regulation of GnRHR mRNA levels correlated with that of α and LHβ but was different from that of FSHβ. This suggests that α and LHβ mRNA levels are maximally stimulated when GnRHR levels are relatively high, whereas FSHβ mRNA levels are maximally stimulated at lower levels of GnRHR expression, and that the mechanism for differential regulation of the gonadotropins by varying pulse frequencies of GnRH may involve levels of GnRHR. Furthermore, these data suggest that the mechanisms whereby varying GnRH pulse frequencies stimulate α, LHβ, and GnRHR gene expression are similar, whereas the stimulation of FSHβ mRNA levels may be different.

scholarly journals Nitric oxide modulation of human leukemia cell differentiation and gene expression

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1880-1884 ◽  
Author(s):  
G Magrinat ◽  
SN Mason ◽  
PJ Shami ◽  
JB Weinberg
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Messenger Rna ◽  
Interleukin 1 ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Tnf Alpha ◽  
Nonspecific Esterase ◽  
Human Leukemia ◽  
Mrna Levels

Abstract Nitric oxide (NO) functions as an intercellular messenger molecule in such varied contexts as neurotransmission, immune regulation, and the control of vascular tone. We report that NO, delivered as purified gas or released from the pharmacologic NO donors sodium nitroprusside or 6- morpholino-sydnonimine, caused monocytic differentiation of cells of the human myeloid leukemia cell line HL-60 and altered gene expression. The treated cells stopped proliferating, became spread and vacuolated, had increased expression of nonspecific esterase and the monocyte marker CD14, and displayed increased capacity to produce hydrogen peroxide. Furthermore, these treated cells had increased steady-state expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF- alpha) and interleukin-1 beta (IL-1 beta), but decreased expression of mRNA for the proto-oncogenes c-myc and c-myb. The increase in TNF-alpha and IL-1 beta mRNA levels was due (at least in part) to a new transcription of these specific mRNAs. NO elaborated in the bone marrow microenvironment may have a role in normal and malignant hematopoietic cell growth and differentiation.

scholarly journals Differential Gene Expression of Steroid 5α-Reductase 2 in Core Needle Biopsies from Malignant and Benign Prostatic Tissue1

1997 ◽  
Vol 82 (7) ◽  
pp. 2210-2214
Author(s):  
Catarina Bjelfman ◽  
Torbjörn G. Söderström ◽  
Einar Brekkan ◽  
Bo Johan Norlén ◽  
Lars Egevad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Mrna Level ◽  
Transrectal Ultrasound ◽  
Mrna Levels ◽  
Prostate Hyperplasia ◽  
Noncancerous Tissue ◽  
Core Needle ◽  
Total Rna ◽  
Prostate Diseases

Androgens are implicated in the development of prostate cancer (CAP) and benign prostate hyperplasia. The conversion of testosterone to the more potent metabolite dihydrotestosterone by prostate-specific steroid 5α-reductase type 2 (5α-red2) is a key mechanism in the action of androgens in the prostate and is important in the promotion and progression of prostate diseases. Manipulation of the turnover of androgens is thus fundamental in the pharmacological treatment strategy. We have developed a sensitive solution hybridization method for quantification of the gene expression of 5α-red2 in core needle biopsies of the prostate. The 5α-red2-specific messenger RNA (mRNA) levels were measured in 50 human prostate transrectal ultrasound-guided core biopsies obtained from 31 outpatients (median age 72, range 57–88 yr) undergoing biopsy for diagnostic purposes. Significant differences were observed in the gene expression of 5α-red2 between cancerous and noncancerous tissue. In the 14 biopsies judged cancerous, the median 5α-red mRNA levels were 3.5 amol/ng total RNA compared with 12.0 amol/ng total RNA in the biopsies showing no cancer (P = 0.0018). The median 5α-red2 mRNA level in noncancerous tissue was thus 3.4 times higher than in the cancerous specimens.

scholarly journals Regulation of c-jun gene expression in human T lymphocytes

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1540-1548 ◽  
Author(s):  
D Chauhan ◽  
SM Kharbanda ◽  
E Rubin ◽  
BA Barut ◽  
A Mohrbacher ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Messenger Rna ◽  
Jurkat Cells ◽  
Pokeweed Mitogen ◽  
Mrna Levels ◽  
Dependent Manner ◽  
B Cell Differentiation ◽  
Normal Peripheral Blood ◽  
Mrna Induction

Abstract The present studies have examined the effects of mitogens on induction of early response gene expression in normal peripheral blood T and Jurkat cells. Pokeweed mitogen (PWM) or anti-CD3 significantly increases c-jun messenger RNA (mRNA) levels in T cells. This transient PWM-related increase in c-jun transcripts is maximal after 15 to 30 minutes of exposure of T cells to PWM. PWM induces c-jun gene expression in a concentration-dependent manner. Moreover, PWM similarly induces expression of other genes coding for leucine zipper transcription factors, ie, jun-B and c-fos. Nuclear run on assays demonstrate that PWM treatment is associated with an increased rate of c-jun gene transcription. Transient expression assays with c-jun promoter fragments linked to the chloramphenicol acetyltransferase gene suggest that the PWM-induced increase in transcription is mediated by the AP-1 transcription factor complex. Moreover, treatment of T cells with actinomycin D to block further transcription before their culture with PWM suggests that the increase in c-jun gene expression by PWM is also regulated at least in part by a posttranscriptional mechanism. Cycloheximide does not alter c-jun mRNA induction by PWM. Finally, given that PWM induces B-cell differentiation in an interleukin-6 (IL- 6)-mediated, T-cell-dependent manner, the relationship of c-jun and IL- 6 gene expression in PWM-stimulated T cells was examined. The induction of IL-6 mRNA in T cells stimulated by PWM occurs after maximal induction of c-jun mRNA, at a time when the latter is no longer detectable. These findings suggest that PWM induces c-jun gene expression in T cells by a transcriptional and posttranscriptional mechanism and that AP-1 confers PWM inducibility of this gene. Because the IL-6 promoter has several potential transcriptional control elements, one of which is an AP-1-binding site, future experiments will evaluate the role of c-jun in the regulation of PWM-induced IL-6 synthesis by T cells.

scholarly journals Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections

2011 ◽  
Vol 79 (9) ◽  
pp. 3821-3832 ◽  
Author(s):  
Karren M. Plain ◽  
Kumudika de Silva ◽  
John Earl ◽  
Douglas J. Begg ◽  
Auriol C. Purdie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mycobacterium Avium ◽  
Protein Localization ◽  
Clinical Disease ◽  
Intracellular Pathogen ◽  
Mrna Levels ◽  
Content Type ◽  
Mycobacterial Infections ◽  
Indoleamine 2,3 Dioxygenase ◽  
Gene And Protein Expression

ABSTRACTVirulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases.Mycobacterium aviumsubsp.paratuberculosisis an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased inM. aviumsubsp.paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells ofM. aviumsubsp.paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses toM. aviumsubsp.paratuberculosisand other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease.

scholarly journals Periovulatory Expression of Hydrogen Peroxide-Induced Sulfiredoxin and Peroxiredoxin 2 in the Rat Ovary: Gonadotropin Regulation and Potential Modification

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5512-5521 ◽  
Author(s):  
Jae-Il Park ◽  
Hye-Jeong Jeon ◽  
Nak-Kyun Jung ◽  
You-Jee Jang ◽  
Jin-Seon Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chorionic Gonadotropin ◽  
Cumulus Cells ◽  
H2o2 Production ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Peroxiredoxin 2 ◽  
Antioxidant Agents ◽  
Preovulatory Follicles

Abstract Reactive oxygen species are involved in ovulation. The aim of this study was to examine gonadotropin regulation of antioxidant enzyme sulfiredoxin (Srx) and peroxiredoxin 2 (PRDX2) expressions and modification during the ovulatory process in rats. Administration of antioxidants in vivo reduced ovulation rate and cumulus expansion. LH treatment increased H2O2 levels within 15 min, which, in turn, induced Srx gene expression in cultured preovulatory follicles. Treatment of preovulatory follicles with catalase suppressed the stimulatory effect of LH on Akt phosphorylation. LH- or H2O2-stimulated Srx mRNA levels were suppressed by inhibitors of antioxidant agents and MAPK kinase. An in vivo injection of equine chorionic gonadotropin-human chorionic gonadotropin (hCG) stimulated Srx mRNA within 1 h in granulosa but not thecal cells of preovulatory follicles. Srx protein levels were stimulated from 3 h post-hCG injection. Immunofluorescence analysis revealed that oocytes expressed the Srx protein. Furthermore, hCG treatment increased Srx expression in mural granulosa, theca and cumulus cells, but the Srx protein was not detected in corpora lutea. Gene expression of PRDX2, identified as an Srx-dependent modified enzyme, was stimulated by gonadotropins. In situ hybridization analysis demonstrated that PRDX2 mRNA was detected in oocytes and theca cells as well as granulosa cells of some antral and preovulatory follicles. High levels of PRDX2 mRNA were detected in corpora lutea. Total levels of PRDX2 protein were not changed by gonadotropins. However, levels of hyperoxidized PRDX2 increased within 2–3 h after the hCG injection. Taken together, gonadotropin stimulation of Srx expression and PRDX2 modification in the ovary suggest the existence of an antioxidant system to maintain H2O2 production and elimination during the periovulatory period.

scholarly journals Methylation and Gene Expression of BCAT1 and IKZF1 in Colorectal Cancer Tissues

2018 ◽  
Vol 12 ◽  
pp. 117955491877506 ◽  
Author(s):  
Maher Jedi ◽  
Graeme P Young ◽  
Susanne K Pedersen ◽  
Erin L Symonds
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Messenger Rna ◽  
Stage Iv ◽  
Mrna Levels ◽  
Polymerase Chain ◽  
Cancer Tissues ◽  
The Relationship ◽  
Neoplastic Tissues

The genes BCAT1 and IKZF1 are hypermethylated in colorectal cancer (CRC), but little is known about how this relates to gene expression. This study assessed the relationship between methylation and gene expression of BCAT1 and IKZF1 in CRC and adjacent non-neoplastic tissues. The tissues were obtained at surgery from 36 patients diagnosed with different stages of CRC (stage I n = 8, stage II n = 13, stage III n = 10, stage IV n = 5). Methylated BCAT1 and IKZF1 were detected in 92% and 72% CRC tissues, respectively, with levels independent of stage ( P > .05). In contrast, only 31% and 3% of non-neoplastic tissues were methylated for BCAT1 and IKZF1, respectively ( P < .001). The IKZF1 messenger RNA (mRNA) expression was significantly lower in the cancer tissues compared with that of non-neoplastic tissues, whereas the BCAT1 mRNA levels were similar. The latter may be due to the BCAT1 polymerase chain reaction assay detecting more than 1 mRNA transcript. Further studies are warranted to establish the role of the epigenetic silencing of IKZF1 in colorectal oncogenesis.

scholarly journals Expression of Estrogen Receptor α and β in the Rhesus Monkey Corpus Luteum during the Menstrual Cycle: Regulation by Luteinizing Hormone and Progesterone*

Endocrinology ◽  
2000 ◽  
Vol 141 (5) ◽  
pp. 1711-1717 ◽  
Author(s):  
Diane M. Duffy ◽  
Charles L. Chaffin ◽  
Richard L. Stouffer
Keyword(s):  
Estrogen Receptor ◽  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Messenger Rna ◽  
Luteal Phase ◽  
Estrogen Receptor Α ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Protein Levels ◽  
Late Luteal Phase

Abstract There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ERβ, adds an additional level of complexity. To reevaluate ER expression in the primate luteal tissue, we used semiquantitative RT-PCR based assays and Western blotting to assess ERα and β messenger RNA (mRNA) and protein levels in corpora lutea (n = 3/stage) obtained from adult female rhesus monkeys at early (days 3–5), mid (days 6–8), mid-late (days 10–12), and late (days 14–16) luteal phase of the natural menstrual cycle. ERα mRNA levels did not vary across the stages of the luteal phase, and ERα protein was not consistently detected in luteal tissues. However, ERβ mRNA and protein levels were detectable in early and mid luteal phases and increased (P &lt; 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase. To determine if ERβ mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release. Treatment with antide alone or concomitant LH administration did not alter luteal ERβ mRNA levels. When monkeys also received the 3β-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERβ mRNA levels were 3-fold higher (P &lt; 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERβ mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ERβ expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ERβ)-mediated pathway. Increased ERβ expression in the progestin-depleted corpus luteum during LH exposure suggests that the relative progestin deprivation experienced by the corpus luteum between LH pulses may enhance luteal sensitivity to estrogens during the late luteal phase of the menstrual cycle.

scholarly journals Levels of messenger RNA encoding ovarian receptors for FSH and LH in cattle during superovulation with equine chorionic gonadotrophin versus FSH

1998 ◽  
Vol 156 (2) ◽  
pp. 373-378 ◽  
Author(s):  
K Soumano ◽  
JG Lussier ◽  
CA Price
Keyword(s):  
Steady State ◽  
Messenger Rna ◽  
Chorionic Gonadotrophin ◽  
Corpora Lutea ◽  
Mrna Levels ◽  
Slot Blot ◽  
Lh Receptor ◽  
Prostaglandin F2 Alpha ◽  
Steady State Levels ◽  
Slot Blot Analysis

This study tested the hypothesis that luteal LH receptor (LHr) and follicular LHr and FSH receptor (FSHr) steady-state mRNA levels are greater during superovulation with equine chorionic gonadotrophin (eCG) compared with that with FSH. Heifers were stimulated with eCG (n = 10) or FSH (n = 10), and ovaries were recovered the day before and at 12 and 24 h after luteolysis was induced with prostaglandin F2 alpha (PGF2 alpha). Total RNA was purified from individual follicles and corpora lutea. Steady-state levels of LHr and FSHr mRNA were assessed by slot blot analysis employing homologous cDNA probes. There were no differences in luteal LHr between FSH- and eCG-stimulated animals before luteolysis, and hybridization signals were detected in only one of six animals by 12 h after injection of PGF2 alpha. After PGF2 alpha injection, steady-state levels of follicular LHr were 4-fold lower (P < 0.05) and follicular FSHr mRNA levels were 2.4-fold lower (P < 0.05) in eCG- compared with FSH-treated cattle. In eCG-treated animals, induction of luteolysis led to a significant increase in follicular LHr mRNA levels (P < 0.01) and a significant decrease in follicular FSHr mRNA levels (P < 0.01). There was no such effect of luteolysis in FSH-treated animals. We conclude that superovulation with eCG, compared with FSH, results in lower follicular levels of LHr and FSHr mRNA but does not affect luteal LHr mRNA levels.

scholarly journals Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats

2009 ◽  
Vol 37 (3) ◽  
pp. 231-238 ◽  
Author(s):  
Thomas S. Postler ◽  
Murat T. Budak ◽  
Tejvir S. Khurana ◽  
Neal A. Rubinstein
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Protein Localization ◽  
Muscle Growth ◽  
Extraocular Muscles ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Wide Range ◽  
Canonical Pathways

Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently affected by thyroid-associated diseases, little is known about the direct effects of thyroid hormone on these muscles. To create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of the thyroid hormone 3,3′,5-triiodo-l-thyronine (T3); subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated control animals. The expression of 468 transcripts was found to be significantly altered, with 466 of these transcripts downregulated in EOMs from T3-treated animals. The biological processes into which the affected genes could be grouped included cellular metabolism, transport, biosynthesis, protein localization, and cell homeostasis. Moreover, 15 distinct biochemical canonical pathways were represented among the genes with altered transcription levels. Strikingly, myostatin ( Gdf8), a potent negative regulator of muscle growth, was found to be strongly downregulated in EOMs from T3-treated animals. Together, these findings suggest that pathological concentrations of thyroid hormone have a unique effect on gene expression in EOMs, which is likely to play a hitherto neglected role in thyroid-associated ophthalmopathies.

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