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ABSTRACT: Estrogen (E) has been shown to play a major role in hypothalamic function and is a prerequisite for progesterone (P) induced sexual behavior in female rats. In the course of studies in search of steroid induced hypothalamic genes, we discovered a surprisingly large number of E-induced genes (21 mRNAs in total). This is the largest number of E-induced genes ever identified in a single organ. Many of these mRNAs exhibit considerable magnitudes of induction and their levels were maintained typically during subsequent P treatment. Among the induced genes, several encode metabolic enzymes and may account for some of the morphological changes observed in hypothalamic neurons in response to E. Since E appears to play a major role in defining the pattern of hypothalamic gene expression in conjunction with its capacity for behavioral modulation, these newly identified cDNAs may serve as genetic markers for correlative studies of E-induced central nervous system behavior.
The Journal of Steroid Biochemistry and Molecular Biology 12/1994; 51(3-4):131-6. · 3.05 Impact Factor
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ABSTRACT: To test further the idea that sexual behavior in rodents is mediated via the progesterone receptor (PR) in the ventromedial nucleus of the hypothalamus, antisense and sense oligonucleotides to progesterone receptor were administered intracerebroventricularly into the third cerebral ventricle of ovariectomized estrogen-primed animals. Progesterone-facilitated sexual behavior was inhibited in animals treated with antisense oligonucleotides, with proceptive and receptive responses being minimal or completely suppressed. Sexual behavior was not altered by control sense oligonucleotides. In vitro binding assays of the cytosol progesterone receptors demonstrated a 52.2% reduction of PRs in the hypothalamus of animals that received antisense oligonucleotides, suggesting a reduction in PR synthesis. These data suggest that a threshold level of estrogen-induced hypothalamic PR is critical in the regulation of progesterone-facilitated sexual behavior in female rats.
Endocrinology 11/1994; 135(4):1409-14. · 4.46 Impact Factor
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ABSTRACT: We have cloned a novel member of the nuclear receptor superfamily that has been identified from complementary DNA libraries derived from mouse tissues using a low stringency cross hybridization strategy. The deduced protein sequence contains 495 amino acids and consists of the characteristic DNA-binding and ligand-binding domains of the nuclear receptor superfamily. The primary sequence of this new orphan is distinct from those of previously cloned members and subgroups. Analysis of the DNA-binding properties of the in vitro synthesized protein revealed that this new orphan receptor binds to the sequence TCAAGGTCA that includes the steroidogenic factor-1 half-site and direct repeat with 0 bp spacing elements. Northern blot and ribonuclease protection assays showed that the receptor was predominantly expressed in the testis. Results from in situ hybridization experiments confirmed this observation and showed it to be located in the spermatogenic cells. High level expression was also detected in developing oocytes in the ovary. Thus, high level expression of this gene is restricted to developing germ cells, the oocytes and spermatogenic cells. We speculate that this orphan receptor may be a molecule involved in regulating some aspect of meiosis, and that the major function of this factor is likely to be involved in the regulation of gene expression in germ cell development during gametogenesis. It has been designated germ cell nuclear factor.
Molecular Endocrinology 11/1994; 8(10):1434-44. · 4.54 Impact Factor
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ABSTRACT: We have cloned a novel member (mTR2R1) of the nuclear receptor superfamily of transcription factors from a mouse brain cDNA library. The cDNA sequence predicts a protein primary structure of 629 amino acids with a calculated molecular weight of 68.8 kDa. The amino acid sequence of the protein contains three regions of consensus sequence that are conserved throughout the nuclear receptor superfamily. One of these regions encodes a type II zinc finger DNA binding domain that is characteristic of this family of transcription factors. Comparison of the amino acid sequence of mTR2R1 with other nuclear receptors indicates that it is most closely related to the orphan receptor, hTR2, and suggests that these proteins constitute a novel subfamily within the nuclear receptor superfamily. mTR2R1 is encoded by two mRNAs that show different but overlapping spatial patterns of expression in the adult mouse. The identification of a subfamily of TR2 receptors together with the existence of variant mRNAs for these receptors prompts a close examination of the tissue-specific regulatory role of this subfamily of nuclear receptors.
Gene Expression 02/1994; 4(1-2):77-84. · 1.31 Impact Factor
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ABSTRACT: Two additional forms of mouse peroxisome proliferator activated receptor have been identified from cDNA libraries derived from mouse tissues using a low stringency cross-hybridization screening method. One is mNUCI, which has 97% amino acid sequence identity with hNUCI in its DNA binding domain. The other one is mPPAR gamma. The full-length cDNA of mPPAR gamma encodes a protein of 470 amino acids in length. The overall amino acid sequence identity is 75% as compared with xPPAR gamma, with the highest homology in the DNA binding region and ligand binding region, 97% and 86% identity, respectively. The discovery of two new forms of mPPAR and the recent cloning of hPPAR provide evidence for the existence of at least five different forms of receptor in the peroxisome proliferator activated receptor subfamily.
Biochemical and Biophysical Research Communications 11/1993; 196(2):671-7. · 2.48 Impact Factor
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ABSTRACT: We have identified and cloned a novel member of the nuclear receptor superfamily. The cDNA was isolated from a mouse brain cDNA library and encodes a protein 598 amino acids in length with a predicted mol wt of 66 kilodaltons. The amino acid sequence of the protein is closely related to an additional family member and immediate early gene product, Nur77, and the novel factor is referred to as Nurr1 (Nur-related factor 1). The relationship between Nurr1 and Nur77 suggests that these proteins constitute an additional subfamily within the nuclear receptor superfamily. Like Nur77, the expression of Nurr1 is induced by membrane depolarization of PC12 cells. However, while Nur77 shows an early transcriptional response to nerve growth factor stimulation, the failure of Nurr1 to respond to this agent suggests a differential selectivity of the two proteins in terms of their transcriptional responses to specific stimuli. Finally, both proteins are differentially expressed during development and in tissues of the adult mouse. Unlike Nur77, Nurr1 appears to be predominantly located in brain tissue, suggesting a primary role for this putative transcription factor in regulation of gene expression in the central nervous system.
Molecular Endocrinology 01/1993; 6(12):2129-35. · 4.54 Impact Factor
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ABSTRACT: Two additional forms of mouse peroxisome proliferator activated receptor have been identified from cDNA libraries derived from mouse tissues using a low stringency cross-hybridization screening method. One is mNUCI, which has 97% amino acid sequence identity with hNUCI in its DNA binding domain. The other one is mPPARγ. The full-length cDNA of mPPARγ encodes a protein of 470 amino acids in length. The overall amino acid sequence identity is 75% as compared with xPPARγ, with the highest homology in the DNA binding region and ligand binding region, 97% and 86% identity, respectively. The discovery of two new forms of mPPAR and the recent cloning of hPPAR provide evidence for the existence of at least five different forms of receptor in the peroxisome proliferator activated receptor subfamily.
Biochemical and Biophysical Research Communications.
