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)

We investigate in this study the hypothesis of human sex steroid-binding protein hSBP internalization into germ cells in a primate model. Human SBP was purified from late-pregnancy serum and labeled either with colloidal gold particles (18 nm) or with [3H]delta 6-testosterone by photoaffinity treatment. The germ cells were isolated from sexually mature monkey testis or caput epididymis (Macaca fascicularis) by mechanical means and cell suspensions (4 x 10(6) per 100 microliters culture medium) were incubated in presence of hSBP-gold complex (60 ng/100 microliters) or hSBP-[3H]delta 6-testosterone complex (66 ng/100 microliters, 20,000 cpm) for 2, 5, 15, 45, and 60 min. The samples were processed for electron microscopy followed by autoradiographic treatment for the radiolabeled samples. Localization of the label occurred over the whole germ cell lineage whichever tracer was used. Spermatogonia, spermatocytes, spermatids, testicular and epididymal spermatozoa exhibited specific binding sites over the plasma membrane associated with clathrin-like coated pits and vesicles. At 34 degrees C, intracellular localization of the labeled ligand was found within coated vesicles, in early and late endosomes. In addition, in early spermatogenic cells, labeled ligand was detected in the nuclei and/or associated with the nuclear envelope whereas in late spermatids and residual bodies, the labeling was accumulated in multivesicular, prelysosomal structures. Quantitative analysis of the "labeled cells/total cells" ratio exhibited a negative correlation to the maturation steps, epididymal spermatozoa being the least labeled. The cellular distribution is similar with one or the other protein in the same spermatogenic cells. Unlabeled hSBP treatment prior to labeled hSBP reduced significantly the internalization. Lowering the temperature to 4 degrees C prevented endocytosis and enhanced membrane binding. EDTA pretreatment strongly decreased hSBP internalization and modified the early endocytic steps, namely, the pinching off of the coated vesicles. It is concluded that monkey germ cells are able to internalize the human sex steroid-binding protein through specific endocytic organelles. This endocytosis leads to the labeling of the nuclei in the early spermatogenic cells and of the multivesicular bodies in the late germ cells. This strongly suggests that steroid-binding proteins may be required for spermatogenesis in acting at the germ cell lineage level either by themselves or by serving as steroid transmembrane carriers.
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PMID:Endocytosis of human sex steroid-binding protein in monkey germ cells. 178 75

Human sex steroid-binding protein (hSBP) has been purified from late-pregnancy serum and labelled either by iodination (125I) or by photoaffinity with [3H]delta 6-testosterone. Using a micromanipulator, each labelled protein was separately injected into the lumen of epididymal tubules isolated from the head epididymis of the cynomologus monkey (Macaca fascicularis). Tubules were sampled from 3 to 90 min after the injection and processed for electron microscope autoradiography. Localization of the label occurred over the epididymal epithelium whichever tracer was used. The labelling was not randomly distributed over the different cell types constituting the epithelium, since only the 'principal cells' exhibited a silver grain count significantly greater than the background count. In these cells, labelled protein was found over endocytic organelles (coated structures, endosomes, multivesicular bodies and the trans Golgi network) and nuclei (including the nuclear envelope). Quantitative analysis demonstrated the same pattern of cellular and subcellular distribution for each tracer. Pretreatment with excess unlabelled protein significantly reduced the uptake of radioactivity by the principal cells, demonstrating the specificity of this phenomenon. This is the first study to show direct histological evidence for the internalization of hSBP in the primate epididymis, consistent with earlier immunohistochemical or biochemical localization of this protein. It is concluded that head epididymal cells are able to take up labelled hSBP across their apical membrane. The mechanism of internalization seems to involve endocytosis by the principal cells and leads to labelling of the nuclear compartment. This is strikingly similar to the pattern of uptake of rat androgen-binding protein (rABP) by rat epididymal cells previously demonstrated by our group. To what extent the chemical and structural homology between hSBP and rABP can be held responsible for the common cytophysiological behaviour of these sex steroid-binding proteins remains to be determined.
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PMID:Internalization of human sex steroid-binding protein in the monkey epididymis. 212 29

Previous experiments have shown that androgen binding protein (ABP) and androgens exist in high concentrations in the tissue and the lumen of the rat caput epididymis. The present experiments were performed to determine whether or not intraluminal APB affects tubule net uptake of androgens. Caput epididymal tubules were dissected into 2-cm segments, subjected to microperfusion into the tubule lumen, and incubated for 2.5 h in 35 degrees C minimum essential medium (MEM) containing 2.0 ng tritiated testosterone (3H-T) per ml. 14C-polytheylene glycol [PEG] was included as a contamination marker. In the first series of experiments, caput tubules were perfused with a control, artificial perfusion (MKB) containing no ABP or fresh rat rete testis fluid (RTF), which is known to contain ABP. Tubules incubated while containing RTF took up 138% of the tritiated androgens taken up by control tubules. In the second series of experiments, tubules were perfused with fresh caput epididymal lumen content, MKB alone, MKB containing either 5.0 ng purified rat ABP/microliters or 50 ng ABP/microliters. Tubules incubated while containing perfused MKB took up only 47% of the tritiated androgens taken up by tubules containing perfused native lumen content. Increasing intraluminal ABP concentrations in the MKB medium increased 3H-androgen uptake in a stepwise fashion. Intraluminal ABP at a concentration of 50 ng/microliters was associated with a 71% return of 3H-androgen uptake towards that amount of 3H-androgen taken up by tubules perfused with native lumen content. Intraluminal ABP enhances net androgen uptake by caput epididymal tubules from their surrounding medium in vitro.
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PMID:Intraluminal androgen binding protein alters 3H-androgen uptake by rat epididymal tubules in vitro. 227 22

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

An androgen binding protein (ABP), with an equilibrium dissociation constant of 4.2 nM and a molecular weight of about 100 kDa, has been purified from bull epididymal extracts using a four-step procedure. These preliminary results underline the main difficulties encountered in the purification of this protein present at a very low concentration (i.e. 50-fold less than in rat or rabbit epididymides). Ammonium sulfate precipitation is not a suitable step due to the formation, in presence of salt, of insoluble material leading to a loss of ABP. Lipids, particularly phospholipids, might be implicated in this phenomenon. Several steps, including anion exchange in batch followed by concentration, affinity chromatography and HPLC gel filtration allowed us to obtain a 7667-fold purified protein with a 9% yield.
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PMID:Partial purification of androgen binding protein from bull epididymis. 230 43

Purified rabbit epididymal androgen binding protein and serum testosterone estradiol binding globulin have been immunologically compared. A comparison using the steady state gel method of Ritzen et al. indicated immunological cross-reactivity. In order to further compare their immunological properties we developed a radioimmunoassay for both rbABP and rbTeBG using specific antisera directed against each. When these assays were compared, the extent or completeness of displacement proved to be the only parameter that was significantly different. This data obtained with homologous and heterologous radioimmunoassays is consistent with the idea that these two proteins contain minor antigenic determinants which are distinct.
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PMID:Comparison of rabbit epididymal androgen binding protein and serum testosterone estradiol binding globulin--II. Immunological properties. 242 99

A sustained-release formulation of a potent gonadotropin-releasing hormone (GnRH) agonist, Zoladex (D-Ser(But),6 Aza Gly10-GnRH; ICI 118,630; goserelin), was administered subcutaneously (3.6 mg/depot) to male rats once every 28 days for 2-24 wk to determine the extent to which pituitary-testis function could be suppressed and whether suppression was maintained throughout the period of treatment. Administration of Zoladex resulted in sustained decreases in weight of the testis, epididymis, seminal vesicles and prostate gland. The decreases were apparent within 2 wk of initiating treatment. Patchy degeneration of the seminiferous tubules and atrophy of the Leydig cells were observed, but did not progress beyond the degree observed after 1 month of treatment. Serum and testis testosterone were markedly depressed after 2 wk of treatment, as was testis [125I]hCG binding. Serum gonadotropins were also reduced by treatment. Serum androgen binding protein (ABP) was elevated, testis ABP content remained unchanged, and epididymal ABP content was reduced. The changes are consistent with the hypothesis that this compound affects both the anterior pituitary gland and the testis. These findings indicate that depot delivery systems are a convenient way to administer GnRH analogs for sustained treatment schedules.
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PMID:Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonist. 253 93

Continuous low-dose gamma-irradiation of mature rats induced a progressive degeneration of the germ cells. Blood FSH increased by 127, 176 and 214%, respectively, after 55, 70 and 85 days of treatment when compared to FSH levels in control rats (8.50 +/- 0.60 ng/ml); conversely, serum LH and testosterone levels were unchanged. The Sertoli cell function was affected by the treatment from 70 days on, as attested by androgen binding protein (ABP) and transferrin secretions which diminished 35-40%. Serum ABP levels were not altered, whatever the duration of irradiation, even though epididymal ABP contents (as well as concentrations) diminished 34-60% when compared to those of the controls. Moreover, in purified Leydig cells, LH-stimulated intracellular cAMP levels, which were decreased by seminiferous tubule medium (STM) from control rats, were enhanced in presence of STM from treated animals. Testosterone output was stimulated 9-fold in presence of oLH and further increased (46-76%) from stages XIV-V by STM prepared from control and irradiated rats, respectively. After 85 days the STM effects on both cAMP and testosterone syntheses were zero. These results demonstrate a probable alteration of Sertoli cell function after irradiation, but also a role of the germ cells in the regulation of the synthesis of ABP, transferrin and Sertoli cell paracrine factors.
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PMID:Effect of continuous low-dose gamma-irradiation on rat Sertoli cell function. 314 90

Dihydrotestosterone (DHT) is essential for sperm maturation within the epididymis, but the roles of estradiol-17 beta (E2) and progesterone (P) in epididymal function are unknown. To identify sites of potential action of these hormones, and any effect of season on their concentrations, specific binding of steroids to receptors in extracts of ram epididymal tissue was quantified in two studies. Tissue was taken from three broad regions of the epididymis (caput, corpus, and cauda; Study 1) or from seven discrete regions of the epididymis (Study 2) in February to May (nonbreeding season; NBS) or late August to October (breeding season; BS). Specific binding of P was not detected. Saturable high-affinity binding sites specific for DHT (Ka = 2.6 x 10(8).M-1) and E2 (Ka = 5.4 x 10(8).M-1) were detected. Binding was not to androgen-binding protein, testosterone-estradiol-binding globulin, or sperm nuclei. There was no regional or seasonal difference in affinity of DHT or E2 binding. In both studies, concentration of DHT-binding sites (fmol/mg protein for low- plus high-salt extracts) was higher (p less than 0.05) in the BS than NBS. In Study 1, mean concentration of DHT-binding sites was higher (p less than 0.05) in the caput than in the corpus and cauda. The more definitive localization possible in Study 2 revealed that concentration of DHT-binding sites was highest in the distal caput, lowest in the proximal cauda (p less than 0.05), and intermediate in other regions. For E2, however, concentration of binding sites was higher (p less than 0.05) in the BS than NBS only in Study 1, and was higher (p less than 0.05) in the cauda or corpus than in the caput epididymidis. In Study 2, the season by region interaction was significant (p less than 0.05); concentration of E2-binding sites was higher in the distal cauda during the NBS. These data support the concept that the central caput through proximal corpus epididymidis are most dependent on androgenic stimulation, whereas distal regions may respond to estrogenic stimulation.
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PMID:Regional and seasonal differences in concentrations of androgen and estrogen receptors in ram epididymal tissue. 340 73

The toxic effects of doxorubicin on the reproductive system of the male rat were studied at different susceptible stages of postnatal development. A multidisciplinary approach including the assessment of histopathological, functional and biochemical parameters was chosen. Groups of male rats were treated once with the compound (3 mg/kg) on postnatal day 6, 16, 24 or 45. Both the onset of reproductive capacity and fertility were determined by serially mating ten animals per group for 12 weeks beginning at the age of 45 days. Reproductive organ weights, sperm counts and epididymal androgen binding protein (ABP) were measured at intermediate (80-day-old rats) or terminal sacrifice (129-day-old rats). Age dependent differential doxorubicin toxicity was evident. Treatment of 6-day-old animals with doxorubicin severely impaired development of reproductive functions. Treatment of 16-day-old animals reduced fertility throughout the mating study, as well as body and reproductive organ weights and sperm counts. Initial toxicity was observed in the group treated at 24 days of age; particularly, low reproductive organ weights and low sperm counts were found. These findings proved reversible towards the end of the study. Neither biochemical nor functional impairment of the reproductive system could be observed in the group treated at 45 days of age.
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PMID:Differential susceptibility of immature rat testes to doxorubicin at critical stages of maturation. Biochemical and functional assessment. 366 16


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