Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FK143 is a nonsteroidal new inhibitor of steroid 5 alpha-reductase, an enzyme which converts testosterone into 5 alpha-dihydrotestosterone (DHT). We studied in vivo effects of FK143 on rat and dog prostates. FK143 was orally administered to mature male rats for 14 days. At doses above 1 mg/kg, FK143 significantly reduced the wet weights of the ventral prostate and seminal vesicle, but showed no effects on those of the epididymis, testis, and adrenal. Growth of ventral prostate and seminal vesicle was induced by the subcutaneous injection of testosterone propionate (TP) in the castrated young rats and was reduced by FK143 administration at doses above 3.2 mg/kg, while growth induced by 5 alpha-dihydrotestosterone propionate (DHTP) was not affected. FK143 had no binding affinity for the rat androgen receptor. FK143 showed neither estrogenic and antiestrogenic effects on the rat uterus nor androgenic effect on the rat prostate. Concentration of testosterone and DHT in the rat and dog prostates were measured by GC-MS, and administration of 10 mg/kg of FK143 significantly reduced the intraprostatic concentration of DHT. These results indicate that FK143 reduced the prostate growth by inhibiting 5 alpha-reductase activities in the prostates.
J Steroid Biochem Mol Biol 1995 Apr
PMID:FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (2) In vivo effects on rat and dog prostates. 773 5

Searching for hormone-regulated genes in testicular Sertoli cells, we cloned and sequenced a cDNA of 3108 base pairs, named LRPR1 (signifying leucine-rich primary response gene 1). This cDNA sequence has an open reading frame of 2238 base pairs encoding a leucine-rich protein of 746 amino acid residues with a relative molecular mass of 85.6 kDa. As much as 16% of the amino acid residues is leucine. Database analysis revealed significant similarity of LRPR1 to the human brain cDNA sequence EST00443, but not to any other sequences present in databases. The expression of LRPR1 mRNA in Sertoli cells is strongly and rapidly up-regulated by follicle-stimulating hormone (FSH). The level of LRPR1 mRNA was very low in Sertoli cells isolated from 21-day-old rats and cultured for 3 days in the absence of FSH, but LRPR1 mRNA expression was markedly increased within 2 h after addition of FSH to these cultures. A maximal response was reached within 4 h. Dibutyryl-cyclic AMP [(Bu)2cAMP] and forskolin had similar effects compared to FSH, indicating that cAMP acts as a second messenger in the regulation of LRPR1 expression. The up-regulation of LRPR1 mRNA expression by FSH was also observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that FSH regulates LRPR1 mRNA expression through a direct mechanism which does not require de novo protein synthesis. Thus, LRPR1 represents a primary response gene in FSH action on Sertoli cells. The presently available data indicate that LRPR1 mRNA expression is regulated specifically by FSH, since several other hormones and growth factors did not affect LRPR1 mRNA expression in the cultured Sertoli cells. LRPR1 mRNA expression is relatively high in testis, ovary and spleen. A much lower mRNA level was found in brain and lung, and no expression was detected in liver, kidney, heart, muscle, pituitary gland, prostate, epididymis and seminal vesicle. The basal level of testicular LRPR1 expression in intact 21-day-old rats was markedly increased within several hours after a single i.p. injection of FSH, indicating that in vivo LRPR1 mRNA expression may appear to be a useful parameter to evaluate testicular FSH action.
Mol Cell Endocrinol 1995 Feb 27
PMID:Regulation of gene expression in Sertoli cells by follicle-stimulating hormone (FSH): cloning and characterization of LRPR1, a primary response gene encoding a leucine-rich protein. 775 24

An abundant cellular and secretory product of isolated seminiferous tubules from adult rats was identified as having an apparent molecular weight of approximately 24,000 and a pI of 5.3 on autoradiographs of two-dimensional polyacrylamide gels. A protein with identical migration characteristics was identified as a major secretory product of isolated round spermatids. Microsequencing revealed that the protein had homology to phosphatidylethanolamine binding protein (PEBP) identified in rat brain. Primers were used in conjunction with RTPCR to amplify a partial cDNA which was used to probe a rat testis library to obtain full length clones. On Northern blots, PEBP mRNA was abundant in adult rat testis and epididymis and fractions enriched in germ cells but was very low/absent from fetal or immature rat testis or adult rat Sertoli cells. In situ hybridisation identified that abundant mRNA was first detectable in pachytene spermatocytes at stage VII and thereafter at particularly high levels in round and elongating spermatids until step 14. Proteins with significant sequence homology to the rat testis PEBP have been identified previously in mouse testis and epididymis, in rat germ cell cultures and coating the surface of mature rat sperm. Differences in the timing of expression of the PEBP mRNA (first expressed in pachytene spermatocytes) and secretion of the PEBP protein (not a major secretory product until round spermatids) is consistent with PEBP mRNA undergoing delayed translation. The role(s) of secreted lipid binding proteins in spermatogenesis are discussed.
Mol Cell Endocrinol 1995 Feb
PMID:Phosphatidylethanolamine binding protein is an abundant secretory product of haploid testicular germ cells in the rat. 776 34

Previous work has identified a prominent 22-24-kD protein that is present in rat male reproductive tissues, including epididymis and testis (Brooks, 1985; Jones and Brown, 1987; Moore et al., 1987). Using a monoclonal antibody (designated mAb-B109) against this 24-kD antigen (referred to as B109), we have isolated the protein using a combination of chromatofocusing and electroelution from SDS-PAGE gels, and reverse phase HPLC. B109 (pI = 4.8) is amino-terminal blocked. To obtain internal amino acid sequences, the isolated protein was cleaved either with cyanogen bromide in 70% formic acid or with TLCK-treated chymotrypsin. With cyanogen bromide treatment, two peptides, 17.8 kD and 11.9 kD, were isolated and partial amino acid sequences obtained. Chymotryptic peptides were isolated by reverse-phase HPLC and two were chosen for sequence analysis. A computer search for sequence homology through the protein identification resource (PIR) matched B109 to a basic 21-kD cytosolic protein (pI = 7.4) found in bovine brain (> 80% homology). When peptide sequence differences obtained in the present study were substituted into the 21-kD cytosolic protein sequence obtained from the PIR using Intelligenetics software, the calculated pI dropped from 7.4 to 5.8, suggesting that pI differences between the bovine and rat molecules are the result of amino acid substitutions in the testis protein and not tissue-specific posttranslational processing. It has been postulated that the 21-kD bovine brain protein is associated with phospholipid transport, although the function of B109 is unknown.
Mol Reprod Dev 1994 Nov
PMID:Putative rat sperm lipid-binding protein: isolation and partial characterization. 788 68

A method for objective quantification of hamster sperm movement parameters as an indicator of maturation along the epididymis was established using a computerised system. Analysis of spermatozoa released into medium from five epididymal regions showed that the most drastic increases in percentage motility and curvilinear velocity (VCL) occurred from the distal corpus to the beginning of the proximal cauda and in straight-line velocity (VSL) from the beginning to a more distal site within the proximal cauda region. Both high osmolarity (400 mOsm/kg) and the thiol-oxidising agent diamide (10 microM) increased flagellar straightness of distal corpus spermatozoa, but VSL was increased only with the latter. The thiol-reducing agent dithiothreitol (DTT, 1mM) stimulated and maintained percentage motility and velocities of spermatozoa from the caput, stimulated only percentage motility of distal corpus sperm, but decreased velocities of those from the proximal cauda in prolonged incubation. In rats, diamide increased path straightness but not velocities of caput spermatozoa and yet caused immotility within 15 min, whereas DTT prolonged the maintenance of in vitro motility. The slight increases in kinematic parameters in the presence of DTT were enhanced by a 2-min preincubation with diamide. The finding that the effects of DTT and diamide were not compensatory suggests that the influence of the SH/S-S status on sperm movement is multifaceted, with decreasing sensitivity to stimulation upon sperm maturation.
Mol Reprod Dev 1994 Jul
PMID:Maturation of hamster epididymal sperm motility and influence of the thiol status of hamster and rat spermatozoa on their motility patterns. 791 86

The binding of human sex hormone-binding globulin (hSHBG) to plasma membranes prepared from the adult rat epididymis and other potential target and non-target tissues was examined. Specific binding sites were detected in the epididymis, testis, prostate, skeletal muscle and liver. The first three organs exhibited a higher (KD approx. 0.1 nM; Bmax approx. 0.05-0.10 pmol/mg membrane protein, Site I) and a lower (KD approx. 5 nM; Bmax approx. 1.0-2.5 pmol/mg membrane protein, Site II) affinity binding site. Only Site I was detected in muscle membranes and only Site II was detected in membranes isolated from liver. Specific binding was not detectable in either spleen or brain. Regional distribution of hSHBG binding sites occurred in the epididymis. Both Site I and Site II were present in the proximal caput and distal cauda. The distal caput and proximal cauda contained only Site II; no specific binding was detected in the corpus. Binding of hSHBG to epididymal membranes was time- and temperature-dependent. The presence of Ca2+ did not affect binding. Non-liganded [125I]-labeled hSHBG can bind to both sites in epididymal membranes. The affinity of hSHBG for Site I increased 2-fold when it was complexed with 5 alpha-dihydrotestosterone, testosterone or estradiol. The hSHBG-androgen complex had little effect on Site II versus steroid-free SHBG. However, the affinity of the hSHBG-estradiol complex for these sites was increased 10-fold. Cortisol, which has a low affinity for hSHBG, did not influence its binding to either the higher or lower affinity membrane sites.
J Steroid Biochem Mol Biol 1994 Oct
PMID:Interaction of sex hormone-binding globulin with plasma membranes from the rat epididymis and other tissues. 794 46

Based upon findings that the scatter factor/hepatocyte growth factor (SF/HGF) has strong mitogenic and motogenic properties, and that the sperm cell acquires its fertilizing capacity and motility in the distal parts of mammalian epididymis, the present study was conducted to investigate the role of SF/HGF in initiation of sperm cell motility. This was investigated by determining the expression of SF/HGF in various regions of the murine male genital tract by scatter and cell tracking assays using MDCK epithelial cells, Western blot procedure, and the immunohistochemical procedure using paraffin sections of various regions of the male genital tract. The findings from all these assays indicate that SF/HGF is differentially expressed in various parts of the male genital tract with slight or no expression in the testes, caput epididymis, and vas deferens, and with the highest expression in cauda and corpus (distal) epididymis followed by expression in the corpus (proximal) epididymis. This region-specific SF/HGF expression pattern coincides with the pattern of acquiring the fertilizing capacity and motility by the sperm cell during its transit through the male genital tract. However, wherever SF/HGF was expressed in the male genital tract, its molecular weight was slightly higher (Mr, 82 kD), compared to the SF/HGF expressed in various other somatic tissues (Mr, 78 kD), indicating that the genital tract SF/HGF may be a different molecular species that shares some immunoreactive epitopes with the somatic cell SF/HGF. Incubation of immotile sperm from caput epididymis with the purified human placental SF/HGF of 78 kD initiated motility in 5-15% of sperm population. These results strongly suggest that the SF/HGF-like activity is expressed in the male genital tract in a region-specific manner, and this activity may have a role in initiation of sperm motility acquired during its transit through the epididymis in mammals.
Mol Reprod Dev 1994 Aug
PMID:Expression of scatter factor/hepatocyte growth factor is regionally correlated with the initiation of sperm motility in murine male genital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility? 798 Sep 52

Clusterin, also known as sulphated glycoprotein-2 or testosterone-repressed prostate message-2, is a ubiquitous protein found in a variety of tissues and species. In the reproductive tract of the male rat, clusterin is regulated in a complex age-dependent and cell-specific manner. It is expressed at high levels in the epididymis and testis and at very low levels in the prostate under basal conditions. The expression of this gene in the prostate and seminal vesicles is associated with androgen withdrawal, while in the testis clusterin mRNA is repressed by cyclic AMP (cAMP). To understand the mechanisms that control the expression of the clusterin gene better, we isolated and characterized the gene encoding rat clusterin, and analysed its cytosine methylation pattern in various tissues. Several putative regulatory DNA elements were identified, including a consensus AP-1 site in the 5' flanking region. Two AP-1 sites and two transforming growth factor-beta inhibitory elements, one AP-2 site and eight half-sites for glucocorticoid/androgen response elements were found within the first intron, and one cAMP response element was found in the first exon. The cytosine methylation pattern indicated that testicular or epididymal DNA in the rat is hypomethylated in the region between positions -534 and -99 of the clusterin gene, when compared with tissues with lower levels of expression such as prostate as well as liver, lung, kidney and spleen.
J Mol Endocrinol 1994 Aug
PMID:Regulators for the rat clusterin gene: DNA methylation and cis-acting regulatory elements. 799 55

We used two-dimensional gel electrophoresis to analyse the 35S-labelled proteins secreted in vitro by the epithelium of the epididymis. Polypeptides with molecular weight ranging from 10 to > 200 kDa and isoelectric points from < 4 to 9 were observed. These compounds showed high degree of polymorphism. Some were secreted in distinct zones while others were present in the caput and the cauda epididymis.
Cell Mol Biol (Noisy-le-grand) 1994 Feb
PMID:Analysis by two-dimensional gel electrophoresis of ram epididymal secreted proteins. 800 40

Sex-reversed (Sxr) is a duplication of the sex-determining region of the Y chromosome, which gets transposed to a paternal X chromosome. Chromosomally female (XX) zygotes that receive this XSxr chromosome develop as apparent males. Previous work on XXSxr mice (called pseudomales) showed extracellular matrix (ECM) ultrastructural abnormalities in the epididymis and testis. This study examined the biochemical nature of these abnormalities. More hydroxyproline (an indicator of collagen) was noted in the pseudomale testis and epididymis compared to normal male tissues. Western blot analysis showed increased collagen IV in the pseudomale testis and epididymis. In both the hydroxyproline and collagen IV studies, the epididymis was found to contain higher levels of these substances than the testis for both genotypes. There also appeared to be increased messenger RNA for tissue inhibitor of metalloproteinases (Timp), a regulator of collagen, in the pseudomale testis. Data from these studies seem to indicate that the XXSxr genotype influences ECM deposition and/or turnover and exerts a direct genetic influence on the development of the testis and epididymis. According to the existing paradigm of mammalian sexual development, the epididymis is expected to be normal in the presence of adequate androgenization and independent of chromosomal and genetic sex. The results presented here differ from what would be predicted by this paradigm.
Mol Reprod Dev 1994 May
PMID:Extracellular matrix abnormalities in testis and epididymis of XXSxr ("sex-reversed") mice. 804 59


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