Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotroph tumors predominantly secrete FSH or free gonadotropin hormone subunits and rarely LH. In contrast to normal gonadotrophs, a subset of tumors synthesize FSH beta-subunit (SU) in excess of alpha-SU, and the cause of gonadotropin hormone-SU biosynthetic defects in these tumors is unknown. Gonadotropin-releasing hormone (GnRH) is known to modify gonadotropin hormone-SU biosynthesis and secretion and may be an important determinant of gonadotroph tumor hormone regulation. Data in experimental animals have demonstrated that endogenous expression of GnRH may occur in the pituitary. We therefore determined whether 1) the GnRH gene is expressed in gonadotroph tumors and normal pituitaries using reverse transcriptase (RT)-PCR; 2) the GnRH receptor gene is co-expressed in gonadotroph tumors; 3) an alternative upstream transcriptional start site on the GnRH gene is utilized; and 4) media from primary cultures of gonadotroph tumors have detectable GnRH immunoreactivity by RIA. GnRH messenger RNA (mRNA) was detected in 10/10 gonadotroph tumors, eight of which expressed GnRH-Receptor mRNA. Both mRNAs were detected in all normal pituitaries studied (n = 6). Six of 10 gonadotroph tumors and 3/6 normal pituitaries had GnRH transcripts derived from the upstream transcriptional start site (5'GnRH). GnRH immunoreactivity was detected in overnight media from 3/3 primary gonadotroph tumor cultures (range: 1.89-5.86pg/mL; limit of detection (LD) = < 1.58pg/mL) but was not detectable in control media. This is the first study to demonstrate endogenous GnRH gene expression in human pituitary adenomas and normal human pituitary tissue. The presence of both GnRH and GnRH-Rc suggest that GnRH may be a paracrine/autocrine regulator of cell function in the pituitary and may affect gonadotroph tumor hormone phenotype.
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PMID:Gonadotropin-releasing hormone messenger RNA expression in gonadotroph tumors and normal human pituitary. 855 Jul 98

During the infantile period of the female rat (8-21 postnatal days [PND] of age), there is a dramatic increase in plasma FSH, which is thought to be important in initiating ovarian activity and, perhaps, the onset of puberty. To begin to understand the regulation of this FSH surge, we determined the ontogenetic development of LHbeta, FSHbeta, and GnRH receptor (GnRH-R) mRNA levels in the pituitary gland throughout the infantile period of the female rat. Steady-state mRNA levels were determined by an external standard quantitative reverse transcriptase polymerase chain reaction assay. FSHbeta and GnRH-R mRNA levels increased to peak on PND 12 (p < 0.03). LHbeta mRNA levels remained relatively constant until rising on PND 18. A GnRH antagonist (10-100 microg/animal) was administered daily from PND 8-11 or PND 11-13, and animals were killed on PND 12 or PND 14, respectively. FSHbeta, LHbeta, and GnRH-R mRNAs were not affected by GnRH antagonist treatment. Plasma FSH was selectively reduced in the first group, whereas both plasma LH and FSH were suppressed in the second group. These data indicate that gene expression of LHbeta, FSHbeta, and GnRH-R are differentially regulated in the infantile female rat pituitary. GnRH is involved in regulating the secretion of FSH and LH during the infantile period but not in regulating FSHbeta, LHbeta, or GnRH-R mRNA gene expression.
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PMID:Ontogeny of gene expression in the gonadotroph of the developing female rat. 911 62

The binding of gonadotropin-releasing hormone (GnRH) to its receptor in the anterior pituitary gland is the key molecular interaction regulating the reproductive process of mammals. Here, we report the isolation of a cDNA representing this receptor from rat anterior pituitary and the regulation of expression of its mRNA. The rat GnRH receptor cDNA was composed of 2909 nucleotides and encoded a protein containing 327 amino acids having a seven transmembrane topology. Northern blot analysis on RNA from rat pituitary, ovary and testis showed four different transcripts (5.0, 4.5, 2.5 and 1.3 kb) of which the 5.0 kb form was most abundant. The levels of expression of the transcripts were found to be highest in the pituitary followed by the ovary and the testis (about 40% and 5% compared to pituitary, respectively). Using the more sensitive reverse transcriptase/PCR technique, we also detected GnRH receptor mRNA in the adrenal and the hypothalamus. Measurement of pituitary GnRH receptor mRNA levels (the 5.0 kb form) during the estrous cycle showed the lowest levels at estrus (1.0-fold), a 2.2 +/- 0.57 (mean +/- SEM) -fold increase at diestrus I, a 3.5 +/- 0.41-fold increase at diestrus II, a 2.6 +/- 0.34-fold increase on the morning of proestrus, and a 1.9 +/- 0.25-fold on the afternoon of proestrus. Removal of the ovaries led to a 2.7 +/- 0.29-fold increase in GnRH receptor mRNA levels in the pituitary gland; treatment of ovariectomized rats with estrogen resulted in a significant decrease in GnRH receptor mRNA levels. Our studies demonstrate ovarian regulation of GnRH receptor mRNA expression in the anterior pituitary gland.
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PMID:Rat gonadotropin-releasing hormone (GnRH) receptor: tissue expression and hormonal regulation of its mRNA. 939 47

Six endometrial cancer cell lines (Ishikawa, EIIL, HEC1A, 6, 50 and 59), one breast cancer cell line (MCF-7) and two ovarian cancer cell lines (OVHS-1, HRA) were treated for 24 or 168 h with a gonadotropin-releasing hormone (GnRH) analogue, Buserelin acetate, and the cellular growth profile was studied. All these cell lines except for the HRA line had positive GnRH receptor mRNA expression detected by reverse transcriptase polymerase chain reaction. GnRHa suppressed cell growth after 168 h of exposure, but not after 24 h. Suppression of cell growth by the exposure to cis-platinum (CDDP, 10 nM for 24 h) was significantly increased in the presence of GnRHa for 168 h. The mechanism of this growth inhibition was tested by examining both RNA components of human telomerase (hTR) expression and telomerase activity. The results showed that GnRHa inhibits telomerase activity without altering the RNA component of telomerase expression. The present data suggest that GnRH analogue may modulate endometrial, breast and ovarian cancer cell growth through modifying the telomerase activity. Since GnRHa increased the cytotoxic effects of CDDP and GnRHa is a compound of high patient compliance, the value of GnRHa as a tumor sensitizer to CDDP should be further tested in clinical trials.
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PMID:In vitro effects of gonadotropin-releasing hormone (GnRH) analogue on cancer cell sensitivity to cis-platinum. 1038 Nov 37

The present study examined the effects of continuous treatment with gonadotropin-releasing hormone (GnRH) on GnRH receptor (GnRH-R) mRNA levels in dispersed cultures of rat pituitary cells. Pituitary GnRH-R mRNA levels were determined by competitive reverse transcriptase polymerase chain reaction. When pituitary cells were continuously exposed to a low dose of GnRH (0.2 nM), GnRH-R mRNA levels were transiently increased. The levels of GnRH-R mRNA were significantly increased up to 6 h and diminished to untreated levels by 24 h. Luteinizing hormone (LH) release was also increased significantly up to 12 h, maintaining similar levels in LH release thereafter. When GnRH antagonist ([D-pGlu1, D-Phe2, D-Trp3,6]-LH-RH) was added to the cultures together with GnRH (0.2 nM) for 6 h, the stimulatory effect of GnRH on GnRH-R mRNA levels and LH release was significantly diminished in a dose-related manner. In another experiment, pituitary cells were treated with various doses of GnRH (0.02-200 nM) for a relatively short (6 h) or a longer (24 h) period. When pituitary cells were exposed for 6 h, all doses of GnRH (0.02-200 nM) significantly increased GnRH-R mRNA levels in a dose-dependent manner. By contrast, continuous exposure to GnRH for 24 h was ineffective in changing pituitary GnRH-R mRNA levels at any given doses. These results indicate that the duration of GnRH treatment is critical for upregulation of GnRH-R mRNA by continuous GnRH. When pituitary cells were treated for 6 h with either a continuous mode of GnRH (0.2 nM) or an hourly pulsatile mode of GnRH (0.2 nM, 6 min/h), both treatments significantly augmented GnRH-R mRNA levels. Thus, the modes of GnRH application, if treated for a relatively short period, do not appear to make a significant difference in upregulation of GnRH-R mRNA levels. Collectively, our data provide strong evidence that continuous GnRH application is able to upregulate pituitary GnRH-R mRNA levels, if treated for a relatively short period (6 h).
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PMID:Homologous upregulation of GnRH receptor mRNA by continuous GnRH in cultured rat pituitary cells. 1066 41

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to differentially regulate the expression of the gonadotropin subunit genes in cultures of rat pituitary cells. PACAP is expressed within the hypothalamus, and concentrations of PACAP are 2- to 4-fold higher in the portal circulation than in the general circulation. Therefore, PACAP is a candidate regulator of pituitary function. In the present study, we examined the expression of PACAP mRNA within the paraventricular nucleus (PVN) during maturation (Days 20-60) in the male rat and compared this expression to the levels of the gonadotropin subunits, follistatin, and GnRH-receptor mRNAs within the anterior pituitary. Serum concentrations of FSH and LH confirm the established maturational pattern of divergent secretion of LH and FSH. Northern analysis of the gonadotropin subunit mRNAs revealed that FSHbeta expression parallels FSH secretion whereas LHbeta mRNA concentrations do not change during development. Expression of the GnRH receptor in the pituitary parallels that of FSHbeta. In situ hybridization revealed a developmental pattern of PACAP mRNA within the PVN that is reciprocal to that of FSHbeta. Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total pituitary follistatin mRNA revealed no significant changes; however, semiquantitative RT-PCR analyses revealed the presence of two follistatin mRNA species, one of which, corresponding to follistatin-288, was developmentally regulated. These studies identified a reciprocal relationship between PVN PACAP and FSHbeta gene expression in maturing rats. We propose that PACAP contributes to the selective regulation of FSHbeta expression during maturation in the male rat, perhaps via regulation of follistatin.
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PMID:Differential expression of the pituitary gonadotropin subunit genes during male rat sexual maturation: reciprocal relationship between hypothalamic pituitary adenylate cyclase-activating polypeptide and follicle-stimulating hormone beta expression. 1264 91

Previous studies have indicated that arachidonic acid and its lipoxygenase (LO) metabolites play a role in the post-receptor effects of gonadotropin-releasing hormone (GnRH) but the exact role and nature of these putative eicosanoids remain unclear. The potential role of arachidonic acid and LO in GnRH receptor-mediated signaling was investigated in the LbetaT2 gonadotrope cell line, which expresses gonadotropins (LH and FSH) and GnRH-receptor mRNAs. Western immunobloting of LbetaT2 cell extracts, performed with a murine leukocyte polyclonal antibody against 12-LO, showed a 70-kD band, suggesting the presence of 12-LO protein in these cells. GnRH nearly doubled the release of 12-hydroeicosatetraenoic acid, a product of the 12-LO enzyme, within 10 min. A specific reverse transcriptase polymerase chain reaction with a set of primers based on the reported sequence of rat brain 12-LO yielded a 170-bp band which showed 100% homology with the expected rat brain 12-LO sequence. Exposure of LbetaT2 cells to pulsatile GnRH treatment (10 nM, 90-min interpulse, one and three pulses) led to a approximately 3-fold increase in 12-LO mRNA levels. In conclusion, we provide evidence for the presence of a 12-LO enzyme in LbetaT2 cells, the expression and activity of which are increased by short-term/pulsatile exposure to GnRH. LbetaT2 cells represent a potential model to further study the involvement of 12-LO in GnRH receptor signaling.
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PMID:Gonadotropin-releasing hormone activates the 12-lipoxygenase pathway in the LbetaT2 gonadotrope cell line. 1280 74

The hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) serves a key role in regulating mammalian reproductive function. An extrapituitary role for GnRH in the normal and malignant reproductive tissues has been postulated. The purpose of our study is to demonstrate the presence and levels of GnRH receptor (RGnRH) protein and its mRNA in normal and malignant tissues of ovary. Normal human ovarian tissues (n = 13), as well as epithelial ovarian cancer specimens from stages I-IV (n = 39), were obtained from appropriate patients at operation room. Monoclonal antibodies against RGnRH were used for immunohistochemical evaluation of paraffin-embedded ovarian tissue sections by methods of streptavidin-biotin immunostaining. The molecular size and levels of RGnRH were determined by enhanced chemiluminescence-Western blot assay. The amount of RGnRH mRNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The rate of positive immunostaining in ovarian cancers was 53.8% (21/39). The rate of positive staining in the late stage (stages III and IV) was significantly higher than that in the early stage (stages I and II). A single band of molecular weight of about 60 kDa was detected from protein extracts of ovarian cancer as well as from normal ovary. The mean values of fold increase of signal intensities of 60 kDa detected by Western blots in stages I-IV ovarian cancers were 2.39, 2.42, 2.78, and 3.62, respectively, as compared with normal ovarian tissues. The overall positive rate of Western blot analysis for ovarian cancers was 59% (23/39). The mean values of signal intensity of RT-PCR products of RGnRH mRNA in stages I-IV were 2.24, 2.58, 3.10, and 3.20, respectively. The positive rate of overexpression of RGnRH mRNA in ovarian cancer was 70% (21/30). The differences of mean values of signal intensities of Western blot staining (2.41 versus 2.85) as well as RT-PCR products (2.40 versus 3.11) between the early stage and the late stage of ovarian cancers were statistically nonsignificant. Mechanism of autocrine regulation of tumor growth in human epithelial ovarian cancer can be explained by the coexistence of GnRH, RGnRH, and its mRNA, according to our own and other studies. The level of RGnRH expressed by ovarian cancer might be used for targeting chemotherapeutic agents to those patients who harbor RGnRH-positive tumors.
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PMID:Detection of gonadotropin-releasing hormone receptor and its mRNA in primary human epithelial ovarian cancers. 1522 17

Mammalian gonadotropin-releasing hormone (GnRH) was initially isolated from hypothalamus and its receptor from anterior pituitary, although extrapituitary GnRH receptors have been reported. The aim of the present study was to investigate whether GnRH receptor and its mRNA are expressed in cerebral cortical neurons of rat embryos and adult rats using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The immunohistochemistry and RT-PCR analysis showed expression of GnRH receptor and presence of its mRNA, in both cerebral cortical neurons of rat embryos and cerebral cortical tissues of adult rats. Additional experiments showed a decrease in the receptor mRNA expression when cultured neurons of rat embryos were treated with GnRH. It is possible that the presence of GnRH receptors in cortical neurons of rat may be involved in other physiological roles such as neurohormone or neuromodulator.
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PMID:Expression of gonadotropin-releasing hormone receptor in cerebral cortical neurons of embryos and adult rats. 1711 36

Gonadotophin-releasing hormone (GnRH) peptide released from the terminal nerve (TN)-GnRH neurones of the dwarf gourami primarily modifies the electrical properties of various neurones, including the TN-GnRH neurones themselves. However, our knowledge on the expression of GnRH receptors (GnRHRs) in the TN-GnRH neurones is still limited. Here, we used the single-cell reverse transcriptase-polymerase chain reaction after whole-cell patch-clamp recording to study the distribution of various GnRHR types expressed in the individual TN-GnRH neurones. We found that TN-GnRH neurones express two of the three types of GnRHRs cloned in the dwarf gourami: GnRHR1-2 and -R2, but not -R1-1. Furthermore, in agreement with our previous findings, all TN-GnRH neurones contained mRNAs of salmon GnRH but not chicken GnRH-II.
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PMID:Terminal nerve gonadotrophin-releasing hormone (GnRH) neurones express multiple GnRH receptors in a teleost, the dwarf gourami (Colisa lalia). 1750 41


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