Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Testis, adrenal, ovary and placenta contain a microsomal cytochrome P-450 that is capable of converting progesterone to androstenedione and pregnenolone to dehydroepiandrosterone. This conversion requires 17 alpha-hydroxylation followed by C17,20-lyase activity which are both catalyzed by this one protein. Gene cloning and Northern blotting reveal that, at least in man, the same gene is responsible for both testicular and adrenal enzymes. The enzyme was first purified from neonatal pig testis. Both the testicular and adrenal enzymes show a marked preference for the 5-ene substrate (pregnenolone) in keeping with the extensive use of the 5-ene pathway in that species. Affinity alkylation with 17 alpha-bromoacetoxyprogesterone reveals a conserved cysteine at the active site of the enzyme and confirms the conclusion that a single enzyme catalyzes both reactions. Under some circumstances the enzyme catalyzes only 17 alpha-hydroxylation to permit the formation of the C21 steroid cortisol. The regulation of lyase activity, i.e. the determination of the extent to which the second activity is expressed, results from the availability of P-450 reductase. No doubt the greater concentration of this protein in testicular as opposed to adrenal microsomes (x 3.5) is responsible for the production of androgens in the testis and cortisol in the adrenal. Testicular cytochrome b5 also specifically stimulates lyase activity and also causes the porcine enzyme to catalyze a new reaction, i.e. delta 16-synthetase, resulting in synthesis of the important pheromone androsta-4,16-dien-3-one from progesterone.
J Steroid Biochem Mol Biol 1991
PMID:Cytochrome P-450 C21scc: one enzyme with two actions: hydroxylase and lyase. 195 54

In the course of screening a fetal rat cerebellum cDNA library for developmentally regulated sequences, we have identified a cDNA clone identical in sequence to that encoding a protein originally isolated from thymus, thymosin beta 10. Based on northern hybridization analyses with gene-specific oligonucleotide probes derived from the 3'-untranslated regions of thymosin beta 10 mRNA and the closely related beta 4 mRNA, we showed that both thymosin mRNAs were present at highest levels in fetal cortex and cerebellum but also were present at varying levels in all other fetal tissues examined (thymus, spleen, lung, kidney, adrenal, heart, and liver). Steady-state levels of thymosin beta 10 mRNA in cerebellum declined to negligible levels after day 14 of postnatal development. Its levels exhibited a similar pattern in developing cortex, although the adult cortex had slightly higher thymosin beta 10 mRNA levels. These results suggest that thymosin beta 10 mRNA is subject to strong developmental regulation in the rat central nervous system. Reduction of thymosin beta 10 mRNA levels also was seen during development of kidney, heart, and liver. Levels of both thymosin beta 10 and beta 4 mRNAs remained relatively constant during development of thymus, spleen, and lung. Thymosin beta 4 mRNA levels dropped much less sharply during brain development than did levels of the beta 10 mRNA. Testis and ovary contained the highest relative levels of thymosin beta 10 mRNA among adult tissues, but little thymosin beta 4 mRNA. A novel thymosin beta 10 mRNA species unique to adult testis was detected. These results indicate that both thymosins must function in the development of brain and many other organs, as well as in different subsets of organs in the adult.
J Mol Neurosci 1990
PMID:Developmental expression of mRNAs encoding thymosins beta 4 and beta 10 in rat brain and other tissues. 197 98

Angiotensin-converting enzyme (ACE) is a zinc-containing dipeptidyl carboxypeptidase that catalyzes the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. By analyzing cDNA and genomic DNA, we have constructed a consensus sequence encoding the testis isozyme of mouse ACE. Testis ACE cDNA contains 2,435 base pairs and encodes a protein of 732 amino acids. The N-terminal 66 amino acids are unique to the testis isozyme, while the remaining 666 are identical to the carboxyl half of mouse somatic ACE. The overall conservation of amino acid sequence between the testis isozymes of the mouse, rabbit, and human is 78 to 84%. The conservation of amino acids for the N-terminal domain uniquely expressed within the testis is 63 to 67% between these species. Primer extension and RNase protection experiments show that RNA transcription of the testis ACE isozyme begins 16 or 17 bases upstream from the translation start site. A sequence element resembling a TATA box is found 25 bases 5' of the transcription start site. To create its unique isozyme of ACE, the testis begins mRNA transcription in the middle of the exonic-intronic structure of somatic ACE, within a sequence treated as an intron by somatic tissues. Testis ACE is not the result of alternative RNA splicing but seems due to the start of transcription at a unique site within the ACE gene.
Mol Cell Biol 1990 Aug
PMID:Transcription of testicular angiotensin-converting enzyme (ACE) is initiated within the 12th intron of the somatic ACE gene. 216 36

The expression of testis-specific and adult somatic histone genes in sea urchin testis was investigated by in situ hybridization. The testis-specific histone genes (Sp H2B-1 of Strongylocentrotus purpuratus and Sp H2B-2 of Lytechinus pictus) were expressed exclusively in a subset of male germ line cells. These cells are morphologically identical to replicating cells pulse-labelled with 3H-thymidine. Genes coding for histones expressed in adult somatic and late embryo cells (H2A-beta for S. purpuratus and H3-1 for L. pictus) were expressed in the same germ line cells, as well as in the supportive cells (nutritive phagocytes) of the gonad. All histone mRNAs detected in the male germ lineage declined precipitously by the early spermatid stage, before cytoplasmic reduction. The data suggest that both testis-specific and adult somatic histone genes are expressed in proliferating male germ line cells. Testis-specific gene expression is restricted to spermatogonia and premeiotic spermatids, but somatic histone expression is not. The decline of histone mRNA in nondividing spermatids is not merely a consequence of cytoplasmic shedding, but probably reflects mRNA turnover.
Mol Reprod Dev 1989
PMID:Histone gene expression during sea urchin spermatogenesis: an in situ hybridization study. 262 71

Two monoclonal antibodies have been produced against the human 85,000-molecular-weight heat shock protein (hsp85). One of these, 16F1, cross-reacts with the murine homolog and is shown by peptide map immunoblots to be directed against an epitope different from that recognized by the other monoclonal antibody, 9D2. Both monoclonal antibodies recognize only a single Mr-85,000 species in two-dimensional immunoblots. Immunoprecipitation did not reveal an association of this heat shock protein with any other protein in HeLa cells. Immunoperoxidase staining showed a purely cytosolic distribution at both light and electron microscopic levels and no association with membranes, mitochondria, or other organelles. The 9D2 monoclonal and a polyclonal antimurine hsp85 antibody were used to identify the antigens and to quantitate their levels in a variety of normal tissues by immunoautoradiography. Relative abundance in the various tissues as determined by Coomassie blue staining correlates reasonably well with the immunoreactivity. Testis and brain, for example, have high hsp85 levels, whereas heart and skeletal muscle have little or none. The Mr-85,000 sodium dodecyl sulfate-polyacrylamide gel band in testis and brain lysates was further confirmed to be hsp85 by one-dimensional partial proteolytic peptide mapping. Based on these data and our previous observations showing that synthesis and levels of the protein are altered by depriving cultured cells of glucose, we speculate that intracellular hsp85 levels depend on differences in the intermediary metabolism of glucose in the various tissues. Furthermore, it appears that high basal levels of this heat shock protein may not necessarily protect cells against heat shock, since testis is one of the most heat-sensitive tissues and has the highest hsp85 level.
Mol Cell Biol 1984 Dec
PMID:Quantitation and intracellular localization of the 85K heat shock protein by using monoclonal and polyclonal antibodies. 639 6

Glycol ethers produce both hemato- and testicular toxicity in animals, which is dependent on both the alkyl chain length and animal species used. Ethylene glycol monobutyl ether (2-butoxyethanol, BE) causes hemolytic anemia in rats but not in guinea pigs, and red blood cells from both guinea pigs and humans are minimally affected in vitro by the active metabolite 2-butoxyacetic acid. This demonstrates the importance of animal species selection for assessing human risk to BE exposure. 2-Methoxyethanol (ME) produces testicular lesions in rats characterized primarily by the degeneration of spermatocytes undergoing meiotic division with minimal or no hemolytic changes. Because of the differential hemolytic response to BE between rats and guinea pigs, the present study addressed whether the testicular response to ME was similarly dichotomous. Adult rats or guinea pigs were given a single dose of either 200 or 300 mg ME/kg by gavage, and testicular and hemolytic changes were assessed 24 hr after treatment. Testis histology in rats showed dose-dependent degeneration of dividing spermatocytes in stage XIV tubules as expected, with only minimal hemolytic changes, also as expected. In contrast, no testicular or hemolytic effects were observed in guinea pigs 24 hr after either single ME dose. In a subsequent study, a single dose or multiple (3 daily) doses of 200 mg ME/kg were given, and animals were examined at 4 days after the start of treatment. Testes from rats given both single and multiple ME doses showed, as expected, tubules depleted of spermatocytes and early spermatids. In guinea pigs, spermatocyte degeneration was observed in stage III/IV tubules for both dosing schemes, but was much less severe and widespread and differed from rats in morphological characteristics, specifically in the appearance of nuclear chromatin degeneration. In the rat, degenerating spermatocytes showed uniformly condensed and dispersed chromatin, while in the guinea pig they showed marked chromatin condensation at the nuclear periphery. No hemolytic changes were observed in either species or dosing scheme. In summary, although ME-associated testicular lesions were observed in both species, they differed significantly in onset, characteristics, and severity. Both the nature of the differential testicular response to ME and a comparison to the in vitro human testicular response to the active metabolite 2-methoxyacetic acid are subjects of future study.
Exp Mol Pathol 1994 Oct
PMID:Comparison of the testicular effects of 2-methoxyethanol (ME) in rats and guinea pigs. 785 28

Mitochondrial transcription factor A (mtTFA) is a key activator of mitochondrial transcription in mammals. It also has a role in mitochondrial DNA (mtDNA) replication, since transcription generates an RNA primer necessary for initiation of mtDNA replication. In the mouse, testis-specific mtTFA transcripts encode a protein isoform that is imported to the nucleus rather than into mitochondria of spermatocytes and elongating spermatids. We now report molecular characterization of human mtTFA (h-mtTFA) expression in somatic tissues and male germ cells. Similarly to the mouse, analysis of cDNAs and Northern blots identified abundant testis-specific transcript isoforms generated by use of alternate transcription initiation sites. However, unlike the mouse, none of the testis-specific transcripts predicts a nuclear protein isoform, and Western blot analysis identified only the mitochondrial form of h-mtTFA in human testis. Immunohistochemistry and in situ were used to compare the distribution of mtTFA protein, testis-specific mtTFA transcripts, mtDNA and mtRNA in sections of human testis. Our results show that the mtTFA protein and mtDNA exhibit parallel gradients with high levels in undifferentiated male germ cells and low levels or an absence in different male germ cells. Testis-specific transcripts exhibit the opposite pattern, suggesting that in both humans and mice, these testis-specific mtTFA transcripts down-regulate mtTFA protein levels in mammalian mitochondria. Our findings demonstrate that mtTFA does not have a critical role in the nucleus, suggest a mechanism for reducing mtDNA copy number during spermatogenesis and have implications for the understanding of maternal transmission of mtDNA.
Hum Mol Genet 1997 Feb
PMID:Down-regulation of mitochondrial transcription factor A during spermatogenesis in humans. 906 38

RNA binding proteins mediate posttranscriptional regulation of gene expression via their roles in nuclear and cytoplasmic mRNA metabolism. Many of the proteins involved in these processes have a common RNA binding domain, the RNA recognition motif (RRM). We have characterized the Testis-specific RRM protein gene (Tsr), which plays an important role in spermatogenesis in Drosophila melanogaster. Disruption of Tsr led to a dramatic reduction in male fertility due to the production of spermatids with abnormalities in mitochondrial morphogenesis. Tsr is located on the third chromosome at 87F, adjacent to the nuclear pre-mRNA binding protein gene Hrb87F. A 1.7-kb Tsr transcript was expressed exclusively in the male germ line. It encoded a protein containing two RRMs similar to those found in HRB87F as well as a unique C-terminal domain. TSR protein was located in the cytoplasm of spermatocytes and young spermatids but was absent from mature sperm. The cellular proteins expressed in premeiotic primary spermatocytes from Tsr mutant and wild-type males were assessed by two-dimensional gel electrophoresis. Lack of TSR resulted in the premature expression of a few proteins prior to meiosis; this was abolished by a transgenic copy of Tsr. These data demonstrate that TSR negatively regulated the expression of some testis proteins and, in combination with its expression pattern and subcellular localization, suggest that TSR regulates the stability or translatability of some mRNAs during spermatogenesis.
Mol Cell Biol 1997 May
PMID:Involvement of a tissue-specific RNA recognition motif protein in Drosophila spermatogenesis. 911 41

Recent studies have revealed the expression of multiple putative cytoplasmic dynein heavy chain (DHC) genes in several organisms, with each gene encoding a separate protein isoform. This finding is consistent with the hypothesis that different isoforms do different things, as is the case for the axonemal dyneins. Furthermore, the large number of tasks ascribed to cytoplasmic dynein suggests that there may be additional isoforms not yet identified. Two of the mammalian cytoplasmic dynein heavy chains are DHC1a and DHC1b. DHC1a is conventional cytoplasmic dynein and is found in all organisms examined. DHC1b is expressed in organisms that have multiple dyneins, and has been implicated in the intracellular trafficking of molecules in unciliated and ciliated cells. In the present study, we examined the DHC1b protein from rat testis. Testis cytoplasmic dynein contains a large amount of dynein heavy chain reactive with an antibody raised against a peptide sequence of rat DHC1b. The testis anti-DHC1b immunoreactive protein is slightly smaller than testis DHC1a, as assessed by SDS-PAGE. In Northern blots, the DHC1b mRNA is smaller than the DHC1a mRNA. In sucrose gradients made in low ionic strength, DHC1a sedimented at approximately 20S, and the anti-1b immunoreactive heavy chains sedimented in a broad band centered at approximately 14S. The V1-photolysis reaction of individual sucrose gradient fractions revealed three distinct patterns of photolysis, suggesting that there are at least three separate 1b-like heavy chain isoforms in testis. Using a high-stringency Western blotting protocol, the anti-1b antibody and the anti-DHC2 antibody recognized the same heavy chain and specifically bound to one of the three 1b-like heavy chains. We conclude that rat testis contains three 1b-like dynein heavy chains, and one of these is the product of the DHC1b/DHC2 gene previously identified.
Mol Biol Cell 1998 Feb
PMID:Evidence for four cytoplasmic dynein heavy chain isoforms in rat testis. 945 Sep 51

Antiserum against testis ecdysiotropin isolated from the gypsy moth, Lymantria dispar, reacted with neurons in the protocerebrum, optic and antennal lobes, subesophageal, thoracic and abdominal ganglia, as well as in nerve tracts extending through the optic lobes, tritocerebrum, and interganglionic connectives of the pupal stage of these insects. Testis ecdysiotropin is a peptide required by immature moths to initiate production of testes ecdysteroid, which is necessary for the development of the male reproductive system and initiation of spermatogenesis. Antiserum against testis ecdysiotropin also detected an accumulation of testis ecdysiotripic-like material between the inner and outer testis sheaths of pupae. The localization of this peptide in the imaginal disks of the last larval stage, cells and nerve fibers in the optic and antennal lobes of the pupa of both sexes, as well as in the testes during development of the adult reproductive system indicates that testis ecdysiotropin has a much larger impact on adult metamorphosis than development of the reproductive system and initiation of gametogenesis. Although this peptide may have a modulatory role in the central nervous system (CNS), it may also initiate a cascade of activity required for the development of the adult nervous system, in addition to its role in reproduction.
J Mol Neurosci 1997 Dec
PMID:Immunocytochemical localization of testis ecdysiotropin in the pupa of the gypsy moth, Lymantria dispar (L.) (Lepidoptera: Lymantriidae). 948 21


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