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)

The binding of [3H] delta 6-testosterone photoaffinity-labelled rat androgen-binding protein (rABP) has been studied in an enriched fraction of plasma membranes of epithelial epididymal cells in immature (15 days) and adult rats (40 days). The binding was maximal in less than 30 min and more rapid at 4 degrees C than at 34 degrees C. It was calcium and pH dependent. Scatchard plots of the binding data gave curvilinear plots with two types of binding sites corresponding to a K(ass1) of 18.2 nM-1 and K(ass2) of 1.6 nM-1 (2.2 x 10(11) sites/mg protein and 5.4 x 10(11) sites/mg protein, respectively). In adult rats, only one type of binding site was found, with a K(ass) of 3.7 nM-1 (4.5 x 10(11) sites/mg protein). The number of receptors was 5-fold lower in the cauda than in the caput of the epididymis. The pretreatment of the isolated intact cells with streptozotocin induced a 45% reduction of the binding. Only unlabelled rABP and hSBP (human sex steroid-binding protein) but not other proteins (lactotransferrin, serotransferrin, asialofetuine, fetuine and bovine serum albumin) competed with the labelled ligand to bind plasma membranes. The membrane fraction was solubilized by triton X-100. Its incubation with labelled rABP and hSBP provoked the elution of the tracer as an aggregate into the void volume fraction of superose 6B mini-gel filtration columns. Structural homology between hSBP and rABP could be responsible for the common behaviour of the steroid-carrier molecules for the ABP receptor of rat epididymal epithelial cells.
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PMID:The plasma membrane of epididymal epithelial cells has a specific receptor which binds to androgen-binding protein and sex steroid-binding protein. 131 34

Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of gamma rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in caput epididymis and plasma follicle stimulating hormone, FSH) and Leydig cell parameters (plasma luteinizing hormone, LH, testosterone and prostate and seminal vesicle weights) were determined together with the number of germ cells and Sertoli cells. Irradiation did not affect body weight but significantly reduced testicular and epididymal weights from day 7 and day 15 post-irradiation respectively. The cells killed by irradiation were mainly spermatogonia and preleptotene spermatocytes engaged in replicating their DNA at the time of exposure, but all spermatocytes seemed damaged as they gave abnormal descendent cells. By day 34, only elongated spermatids remained in a few tubules and thereafter very little regeneration of the seminiferous epithelium occurred, except for one rat which showed a better regeneration. Levels of ABP decreased by day 15 when the germ cell depletion had reached the pachytene spermatocytes, whereas FSH and LH levels rose when the number of elongated spermatids decreased. Levels of testosterone and the weight of the seminal vesicles did not change; occasionally, the prostate weight was slightly reduced. These results support our hypothesis that pachytene spermatocytes and elongated spermatids are involved in influencing some aspects of Sertoli cell function in the adult rat.
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PMID:Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions. 177 54

One of the side effects of cisplatinum-based chemotherapy is the impairment of spermatogenic function. In order to understand the mechanisms responsible for this side effect, the present study examined the short- and long-term effects of five daily injections of 2 mg/kg cisplatinum upon the functional normality of Leydig cells and Sertoli cells in intact adult rats, and their relationship with the status of spermatogenesis. Results of the present study demonstrate that cisplatinum treatment resulted in a progressive but reversible loss of germ cells from the seminiferous epithelium. Although testicular testosterone contents reduced transiently after the adminisration of cisplatinum, these testosterone levels are otherwise sufficient to support complete spermatogenesis. Thus, the cisplatinum-induced germinal regression cannot be accounted for by hypoandrogenism. The testicular ABP contents of the drug-treated rats remained unchanged during the treatment period, decreased transiently 30 days after the treatment, and returned to normal 120 days after treatment. A decrease in epididymal ABP content was also noted 10 and 30 days after the drug treatment. These observations suggest that Sertoli cell functions were affected by cisplatinum treatment. The effects of cisplatinum upon Sertoli cells were further demonstrated by the dose-dependent suppression of the production of ABP, lactate, and estradiol in cultured Sertoli cells. In addition, cisplatinum administration resulted in a reversible decrease in pituitary weights and an irreversible decrease in seminal vesicle weights. These results further demonstrate the toxic effects of cisplatinum upon various aspects of the male reproductive system.
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PMID:Acute and chronic effects of cisplatinum upon testicular function in the rat. 225 77

In vitro binding studies demonstrate the binding specificity of a series of 4-aryl-2,6-dimethylpyridines for the rat epididymal androgen binding protein (rABP). The compounds bound competitively to rABP but have very weak or no demonstrable affinity for rat ventral prostate androgen receptor and human sex hormone binding globulin. In particular, compound 11, diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorphenyl]amino]methylene] propanedioate, bound with high affinity to rABP (binding affinity about 1/3 that of the endogenous ligand 5 alpha-dihydrotestosterone). However, additional in vitro binding studies indicated that 11 did not bind to testicular or epididymal ABP from rabbit, rhesus monkey, and human. Nevertheless, the specificity and relatively high affinity of these nonsteroidal compounds make them unique and potentially ideal agents for the study of the role of ABP in spermatogenesis and sperm maturation in the rat.
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PMID:A novel, nonsteroidal inhibitor of androgen binding to the rat androgen binding protein: diethyl [[[3-(2,6-dimethyl-4-pyridinyl)-4-fluorophenyl]amino]methylene] propanedioate. 229 11

Continuous low dose gamma irradiation induces a progressive degeneration of germ cells with a concomittant increase in blood FSH; however, the Sertoli cell function is not too much altered since serum ABP level is normal and it is likely that the decrease of epididymal ABP content is the consequence of a reduction in seminiferous tubule fluid excretion. Obviously, spermatids seems to be involved in the regulation of Sertoli cell ABP synthesis.
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PMID:Changes in androgen binding protein (ABP) production following continuous low dose gamma irradiation (IR) of adult rat. 307 27

Rats aged 10 days (Exp. A), 45 days (Exp. B) and 70-90 days (Exp. C) were given procarbazine intraperitoneally at doses of 30 mg/kg/day for 5 or 9 weeks (Exps A, B, C), or by gavage at doses of 5 mg/kg/day (equivalent to the therapeutic dose in man) and 50 mg/kg/day, for 9 weeks (Exp. B). A significant mortality rate was noted in immature rats (Exp. A) and in animals receiving 50 mg/kg/day orally (Exp. B). In all groups the rate of body weight gain and the weights of the testes and epididymides were reduced. Procarbazine produced disruption of the normal spermatogenetic architecture that was very severe or total in immature rats (Exp. A) and in rats given the drug at 30 mg/kg/day for 9 weeks and the highest dose (50 mg/kg) in Exp. B. Disruption of spermatogenesis was only partial in the other experimental groups. The number of Sertoli cells was not affected by the different treatments, but a Sertoli cell dysfunction (vacuolization, decreased ABP and elevated FSH concentrations), most probably secondary to germ cell degeneration, was demonstrated in those rats presenting the most severe disruption of spermatogenesis (Exp. B: i.p. and gavage, 50 mg/kg for 9 weeks). Leydig cells, always present in the interstitium, were moderately affected (decrease in serum testosterone values) in some groups at all ages whereas epididymal sperm reserves were decreased after 9 weeks (Exp. B: 30 mg/kg, i.p.; 5 and 50 mg/kg, gavage). Moreover, there was a marked fall in the number of fetuses per female mated by males in all experimental groups. We conclude that the effects of procarbazine on male reproductive function were independent of the route of administration, greater before puberty and proportional to the dose administered as well as to the duration of the treatment.
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PMID:Reproductive effects of the anti-cancer drug procarbazine in male rats at different ages. 318 60

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

The present study is based on the comparison between the radioautographic analysis of the fate of the androgen-binding protein purified from rat testes (HPLC) subsequently iodinated and injected into the epididymal lumen using a micromanipulator, and the biochemical analysis of the binding capacities of this molecule to soluble epididymal membrane extracts using HPLC and ultracentrifugation. The various experimental conditions used here allowed to demonstrate that ABP was internalized by the epididymal epithelium and to state that this internalization was not a non specific fluid phase endocytosis but a receptor-mediated-mechanism. Indeed, from a morphological stand point, the labeled ABP was associated rather with the membranes of the endocytic apparatus than with its content. In addition, from the two lumenal cell types able to resorb seminal fluid products, only the principal cells took up the labeled ABP. Our results clearly showed that this internalization was correlated with the presence of a 125I.ABP binding protein. Since the binding of this protein molecule to ABP was saturable and Calcium and pH dependent, it is strongly suggested that this molecule behaves as a receptor, the ligand (or one of the ligands) of which could be ABP.
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PMID:[Endocytosis of the androgen-binding-protein (ABP) by the principal cells of rat epididymis]. 325 98

Androgen binding activity (ABP) was determined in two different fractions of developing rat testicular homogenates: in cytosol (cABP) and in a particulate fraction isolated by differential centrifugation (pABP). Homogenates were prepared under stabilization conditions by adding 350 nM testosterone to the homogenization buffer. cABP and pABP concentrations were maximal in 22- to 32-day-old animals, to decrease thereafter during sexual maturation. However, both cABP and pABP increased with age when results were expressed on a per organ basis. pABP could be solubilized under conditions in which it could retain its binding activity. It was then photoaffinity labeled and chromatographed on a Sephadex G 200 column using cytosolic epididymal ABP as a control. Similarities between cABP and pABP include not only the same androgen binding characteristics but also the same exclusion volume after Sephadex G 200 chromatography. Since pABP is only present in Sertoli cells, it might represent ABP before being secreted. Because of its intracellular localization, it could play a role in the compartmentalization of androgens within the testis.
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PMID:Variations in soluble and particulate ABP of rat testis during sexual development. 350 72

We have studied the acute effect of hOG and testosterone administration to immature rats, on testicular (particulate fraction and cytosol) and epididymal (cytosol) ABP levels. One and four hours after a single dose of 10 IU hCG/rat, ABP concentration decreased slightly in testicular membranes and cytosol, but increased markedly in epididymal cytosol (169 +/- 5 and 182 +/- 5 at 1 and 4 h respectively, compared to 113 +/- 13 fmoles/mg protein in control animals, mean +/- SEM). Since testicular and epididymal concentrations of testosterone increased after hCG, as expected, the effect might have been mediated by gonadotrophin stimulated testosterone production in Leydig cells. To test this hypothesis, the hCG effect was studied in rats that previously had received aminoglutethimide to block steroidogenesis. Under these conditions, hCG failed to increase epididymal ABP. Finally, administration of testosterone propionate was also able to stimulate epididymal ABP, but with delayed response: the increase was observed 4 h after injection (212 +/- 18 compared to 127 +/- 28 fmoles/mg protein in control animals, mean +/- SEM). It is concluded that the hCG-induced increase of intratesticular androgen levels results in rapid passage of ABP from testis to epididymis.
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PMID:Acute effect of hCG on testicular and epididymal levels of androgen binding protein (ABP) in the immature rat. 360


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