Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aromatization was measured in testicular microsomal preparations obtained from rats treated 3--4 days with FSH, hCG, or vehicle, hCG, but not FSH, was found consistently to stimulate testicular aromatase activity at least 10-fold. As a marker for FSH action, epididymal androgen-binding protein was assayed and found to be 3 times higher in FSH-treated rats than in either hCG or control rats. hCG, but not FSH or vehicle, stimulated serum testosterone levels more than 100-fold. In all groups, aromatase activity in the microsomal fraction was at least 6 times higher than that found in the mitochondrial fraction. In experiments in which testicular compartments were separated, microsomal preparations from interstitial tissue of hCG-treated rats had 5--7 times more aromatase activity than microsomes from seminiferous tubules and 2--3 times more activity than microsomes from whole testes. It is concluded the hCG administered in vivo can stimulate testicular aromatase activity in immature rats, and the increase in activity is localized in the interstitial tissue.
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PMID:Testicular aromatization in immature rats: localization and stimulation after gonadotropin administration in vivo. 57 93

Interference with estrogenic and androgenic actions might result in an inhibitory effect of benign prostatic hyperplasia (BPH). In the present study the effects of the treatment of intact, adult beagle dogs with the antiandrogen cyproterone acetate (CPA) and the aromatase inhibitor 1-methyl-ADD either alone or in combination on androstenedione-induced prostate growth and on testes, epididymides, and the pituitary was investigated. 1-Methyl-ADD induced a marked counterregulatory increase in the serum testosterone and dihydrotestosterone (DHT) concentrations leading to hyperplasia of the glandular part of the prostate. However, the aromatase inhibitor antagonized the androstenedione-induced (estrogen-related) stimulation of the fibromuscular stroma of the prostate. CPA caused a complete atrophy of the prostate that was also present after treatment with both the aromatase inhibitor and CPA in spite of a striking elevation of the serum testosterone and DHT levels and in spite of the antagonization of the inhibition of testes and epididymal weight induced by androstenedione plus CPA. This indicates a selective inhibition of the prostate of intact beagle dogs treated with CPA and 1-methyl-ADD.
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PMID:Selective inhibition of androstenedione-induced prostate growth in intact beagle dogs by a combined treatment with the antiandrogen cyproterone acetate and the aromatase inhibitor 1-methyl-androsta-1,4-diene-3,17-dione (1-methyl-ADD). 247 59

Sixteen dicyclohexane derivatives including the parent compound d,1-3,4-bis (4-oxocyclohexyl)-hexane (PRDX) have been synthesized and studied for putative interference with androgen binding to transport proteins, metabolizing enzymes, and receptors from rat tissues. Several of these analogues inhibited competitively the binding of dihydrotestosterone to ABP, the epididymal androgen transport protein. One compound had an affinity for ABP as high as Kd = 70 nM. Some dicyclohexanes also inhibited the aromatase enzyme which catalyses conversion of androgens into estrogens, as well as the NADPH-dependent, particulate form of 3 alpha(beta)-hydroxysteroid dehydrogenase, the enzyme that converts dihydrotestosterone into 5 alpha-androstanediol. For both enzymes the inhibition potency Ki of PRDX was about equal to the Km of the substrate. All of these interactions were specific in that they were modulated by single substitutions on the dicyclohexane molecule and they did not occur with other steroid binding proteins such as 5 alpha-reductase and the intracellular androgen receptor. A conformational study showed that dicyclohexanes can assume a 'steroidoid' conformation that differs from the crystal structure and which could account for the specific interactions with the steroid binding sites described here.
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PMID:Inhibition of steroid-protein interactions by dicyclohexane derivatives. 319 13

This review article discusses a novel nontraditional site of estrogen synthesis and the potential targets of estrogen action within the male reproductive system. Our laboratories have recently demonstrated that developing spermatids in several species contain aromatase, the cytochrome P450 enzyme responsible for converting androgens into estrogens. The enzyme was localized by immunocytochemistry and the protein's presence was confirmed by Western blot analysis. Northern blot analysis and in situ hybridization were used to corroborate the presence of mRNA for aromatase. It appears that the aromatase message precedes the synthesis of the protein, and the protein remains in the spermatids several days after the message disappears. The enzyme is located along the tail of newly released sperm and is active in the epididymal sperm as well as in the developing germ cells of the testis. This unique discovery is the basis for our overall hypothesis that estrogen, synthesized by sperm, plays a role in the regulation of epididymal function proportional to the number of sperm being transported. The presence of an estrogen source within the ductal lumen is of special importance to the study of epididymal function because the regulatory mechanisms in this region remain unclear, particularly for the efferent ductules and initial segment regions, although estrogen receptors have been identified in the ductal epithelium. An understanding of the role that estrogen plays in the function of the epididymis may provide benefits in several areas including the treatment of abnormalities in epididymal function, the potential development of a male contraceptive, and insight into the causes of adult epididymal lesions induced by neonatal exposure to estrogenic compounds such as diethylstilbestrol.
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PMID:Sperm, a source of estrogen. 859 76

Recently we reported that mouse germ cells in the testis contain active P450 aromatase (P450arom), the enzyme that converts androgens to estrogens. This finding suggested that germ cells have the ability to produce estrogen. Further studies have shown that germ cells in the testis of several species contain P450arom. The goal of this study was to determine if epididymal sperm contain P450arom and if P450arom activity in sperm changes during traversion of the epididymis in the adult mouse. P450arom was localized in sperm present in the efferent ductules and epididymis by immunocytochemistry using an antiserum generated against purified human placental cytochrome P450arom. P450arom immunostaining in sperm was most prominent in sperm located in the proximal caput epididymis, decreased as sperm traversed the corpus epididymis, and was only slightly apparent in sperm in the cauda epididymis. The immunolocalization of P450arom in epididymal sperm was supported by the measurement of P450arom activity in sperm by the 3H2O assay. We found that P450arom activity in sperm significantly decreases as sperm traverse the epididymis. Based upon these observations, we conclude that sperm can synthesize estrogen and that the synthesis of estrogen by sperm present in the efferent ductules and caput epididymis could be important in the process of sperm maturation.
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PMID:Mouse epididymal sperm contain active P450 aromatase which decreases as sperm traverse the epididymis. 872 34

Our recent discovery that testicular germ cells and epididymal sperm contain active P450 aromatase suggests that the reproductive tract may be a target for estrogen. Therefore, the objective of this study was to determine if estrogen receptors (ER) are present in the avian epididymis using immunocytochemistry, northern blot analysis, and in situ hybridization. Immunoperoxidase staining for ER was found principally in nuclei of nonciliated epithelial cells of proximal and distal efferent ductules and the epididymis duct. The ciliated cells also appeared to be slightly positive in the efferent ductules. Week immunostaining was also observed in the connective tissue of the epididymis duct. Immunostaining was more intense in epithelial cells of the efferent ductules than in epithelial cells of the epididymal duct of connective tissue cells. Strong specific hybridization signals for ER mRNA corresponded to the same areas exhibiting immunocytochemical localization. The presence of ER mRNA in the epididymis was confirmed by northern blot analysis, which showed a single band corresponding to approximately 7.8 kb, similar to that found in chicken oviduct. Based on these data, we suggest that the efferent ducts of the rooster are a primary target for estrogen and that estrogen may have a role in the regulation of avian epididymal function.
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PMID:Estrogen receptors are present in the epididymis of the rooster. 928 50

Although testosterone is the principal sex steroid produced by the testis, estrogen is known to be produced by both Leydig and Sertoli cells during different developmental periods. Additionally, evidence is unfolding to suggest that germ cells might also participate in the synthesis of estrogen within the male reproductive tract. We have recently reported that the messenger ribonucleic acid (mRNA) for P450 aromatase (P450arom), the enzyme that converts androgen to estrogen, is synthesized by rat germ cells. Therefore, the present study was conducted to determine which germ cell types synthesize active P450arom and to measure the activity of this enzyme in germ cells throughout spermatogenesis and in maturing sperm during epididymal transit. First, P450arom activity was measured in pachytene spermatocytes, round spermatids, and a mixture of round spermatids, elongating spermatids, and residual bodies using the tritiated water (3H2O) assay. Second, sperm isolated from different regions of the epididymis were assayed for P450arom activity. Sperm isolated from the caput epididymis with attached efferent ductules had the higher P450arom activity, whereas sperm isolated from the corpus and cauda epididymides had lower P450arom activity. The decrease in P450arom activity in cauda sperm was further confirmed by immunocytochemistry. On the basis of these observations, we conclude that rat testicular germ cells from pachytene spermatocytes through elongating spermatids and epididymal sperm contain active P450arom and that sperm lose aromatase activity as they mature during epididymal transit. Therefore, both post-pachytene rat germ cells and epididymal sperm are capable of estrogen synthesis and are an additional, potentially significant, source of estrogen in the male reproductive tract.
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PMID:Rat testicular germ cells and epididymal sperm contain active P450 aromatase. 953 93

Aromatase is the terminal enzyme responsible for estrogen biosynthesis; it is present in the endoplasmic reticulum membrane of steroidogenic cells in vertebrates. The aromatase gene is unique and its expression is regulated in a tissue- and more precisely, in a cell-specific manner via the alternative use of various promoters located in the first exons. The aromatase gene expression, and its transduction in a fully active protein not only in somatic cells but also in germ cells of rodent testes on one hand, and the widespread distribution of estrogen receptors (ER alpha and ER beta) in the genital tract of the male on the other hand, are clearly in favour of a physiological role for estrogens in the regulation of mammalian testicular functions. Moreover, the aromatase deficiency is associated for instance with severe bone maturation problems and sterility in mouse and man; but conversely, it is well known that estrogens in excess are responsible for the impairment of spermatogenesis. Therefore these female hormones (or the androgens/estrogens ratio) play a physiological role in the development and maintenance of male gonadal functions and seem to control especially the spermatid production (both qualitative and quantitative aspects) and epididymal sperm maturation.
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PMID:Estrogens and male reproduction. 1083 68

To understand the role of estrogen in testicular and epididymal function of rhesus monkeys, we measured steroids in the spermatic and peripheral venus circulation and aromatase activity and its mRNA in testis and epididymis. Testosterone, estradiol-17beta, and estrone, but not androstenedione, were elevated in the spermatic vein serum compared to the peripheral circulation. Aromatase activity in testis and in caput epididymis (259+/-16 [SEM] vs 274+/-47 fmol of 3H2O/mg of protein/h [n = 10], respectively) was significantly higher (p < 0.01) than in corpus and cauda (124+/-28 and 113+/-33 fmol of 3H2O/mg of protein/h [n = 10], respectively). In the ribonuclease protection assay, two P450arom mRNA transcripts were identified in testis and epididymis. One corresponded with the aromatase full-length transcript and the other was a truncated isoform. The latter was significantly more abundant than the former (p < 0.01). Our results demonstrate that the monkey testis and, to a lesser extent, the epididymis can aromatize androgens. However, in the epididymis, like in some areas of the brain, there was a discrepancy between the aromatase activity and the mRNA. The fact that P450arom mRNA and aromatase activity do not correlate in the epididymis may indicate that aromatase activity is not strictly regulated at the level of RNA expression and that other mechanisms for this regulation should be considered.
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PMID:Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys. 1182 22

The cytochrome P450 aromatase (P450arom) is the terminal enzyme responsible for the formation of estrogens from androgens. According to the age, aromatase activity has been measured in immature and mature rat Leydig cells, as well as in Sertoli cells whereas in pig, ram and human the aromatase is mainly present in Leydig cells. In the rat testis, we have immunolocalised the P450arom not only in Leydig cells but also in germ cells and especially in elongated spermatids. Related to the stage of germ cell maturation, we have shown that the level of P450arom mRNA transcripts decreases, it is much more abundant in younger than in mature germ cells whereas the aromatase activity is two- to four-fold greater in spermatozoa when compared to the two other enriched-germ cell preparations. Moreover, we have reported the existence of alternative splicing events of P450arom mRNA in pachytene spermatocytes and round spermatids giving rise to two isoforms lacking the last coding exon which, therefore, cannot encode functional aromatase molecules. In rat germ cells, the aromatase gene expression is not only under androgen control but also subjected to cytokine (TNFalpha) and growth factor (TGFbeta) regulation. In the bank-vole testis, we have evidenced a synchronisation between a fully developed spermatogenesis and a strong positive immunoreactivity for both P450arom and estrogen receptor (ERbeta) in spermatids. Therefore, the aromatase gene expression and its translation in a fully active protein in rodent germ cells evidence an additional site for estrogen production within the testis. Our recent data showing that human ejaculated spermatozoa expressed specific transcripts for P450arom reinforced the observations reported in germ cells of other mammalian species. Together with the widespread distribution of ERs in testicular cells these data bring enlightenments on the hormonal regulation of male reproductive function. Indeed these female hormones (or the ratio androgens/estrogens) do play a physiological role (either directly on germ cells or via testicular somatic cells) in the maintenance of male gonadal functions and obviously, several steps are concerned particularly the spermatid production and the epididymal sperm maturation.
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PMID:Aromatase expression in male germ cells. 1185 Feb 26


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