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At least 19 recordsLinked to original sources
PubMed1975

Testicular androgen-binding protein (ABP): comparison of ABP in rabbit testis and epididymis with a similar androgen-binding protein (TeBG) in rabbit serum.

Testicular androgen-binding proteins (ABP) in rabbit testis, caput epididymis and efferent duct fluid (EDF) were compared to a similar androgen-binding protein TeBg) in rabbit serum. The affinity of these proteins for 5alpha-dihydrotesterone (DHT) at 0 degrees C (KaABP = 1.6 X 10(9) M-1 and KaTeBG = 1.9 X 10(9) M-1) and their steroid specificities were similar (DHT greater than androstanediol greater than progesterone and androstenedione). ABP and TeBG had also almost identical Stokes radii (42.8 +/- 1.2 and 43.9 +- 0.8 A, respectively), sedimentation coefficients (4.7 +/- 0.2 S and 4.4 +/- 0.2 S, respectively) and electrophoretic mobility (Rf = 0.4 in 6 1/2% polyacrylamide gels). Calculation of molecular weights from Stokes radii and sedimentation rates indicated a molecular weight of 74,000 (69,000-78,000) for TeBG and 76,000 (71,000-82,000) for ABP. The corresponding frictional ratios were 1.61 for TeBG and 1.55 for ABP assuming a partial specific volume (v) of 0.70 cm3/g. Polyacrylamide gel electrophoresis (PAGE) at different gel concentrations gave a mean molecular radius of 2.74 nm, also indicating a molecular weight of about 75,000 (v = 0.70 cm3/g. ABP and TeBG could not be separated by PAGE; however, partial separation of ABP and TeBG was achieved by isoelectric focusing and ion-exchange chromatography on DEAE-cellulose. TeBG focused at pH 5.4, whereas ABP formed a distinct peak of bound radioactivity at pH 4.7. Also by ionexchange chromatography, ABP in both testis and epididymal supernatants was shown to have an apparently higher surface charge than TeBG in rabbit serum. The concentration of ABP in efferent duct fluid (2 X 10(-7) M = 60 pmol/mg protien) was much higher than TeBG in male rabbit serum (5.2 X 10(-8) M = 0.7 pmol/mg protein). These findings ruled against the possibility that ABP in the testis and epididymis could have been derived directly from serum. It is concluded that ABP and TeBG are very similar if not identical proteins both serving as transport and carrier proteins in their respective compartments.

Androstenedione↗
PubMed1975

Androgen-binding proteins in rat epididymis: properties of a cytoplasmic receptor for androgen similar to the androgen receptor in ventral prostate and different from androgen-binding protein (ABP).

The cytoplasmic recptor (CR) in rat epididymal 105,000 g supernatant was separated from the androgen-binding protein (ABP) by gel electrophoresis following labeling with [1,2,6,7-3H]-testosterone in vivo. ABP disappeared from epididymal supernatants after castration of hypophysectomy, while CR remained unchanged. CR was evenly distributed between caput and cauda, while much more ABP was present in caput. Properties of CR in epididymis and prostate were similar and distinctly different from ABP. Binding to CR was destroyed by charcoal treatment (1 mg/mg protein) of supernatant for 0 degrees C for 6 h, heating at 50 degrees C for 30 min, or exposure to the sulfhydryl blocking reagent, p-chloromercuriphenylsulfonate (1mM) at 25 degrees C for 30 min, while binding to ABP was unaffected. The isoelectric pH of CR (5.8) was higher than that of ABP (4.6). Dissociation of radioactive 5alpha-dihydrotestosterone (DHT) from CR and nuclear receptors was extremely slow (half-time at 0 degrees C is greater than 2 days), while dissociation from ABP was rapid (half-time at 0 degrees C is similar to 6 min). Cyproterone acetate (250 mg/100 g body weight) inhibited binding to CR both in epididymis and ventral prostate but did not affect binding to ABP. Nuclear uptake was inhibited by cyproterone to the same extent as binding to CR, indicating that nuclear uptake and binding are dependent on CR and independent of ABP. The time-course of uptake and binding in epididymal supernatant and nuclear fractions was essentially the same 1 day after bilateral castration when both CR and ABP were present or 8 days after castration when CR alone was present. It is concluded that the cytoplasmic receptor for androgen in rat epididymis has properties very similar to the androgen receptor in ventral prostate but different from ABP.

Androstenedione↗
PubMed1976

Regulation by FSH and dibutyryl cyclic AMP of the formation of androgen-binding protein in Sertoli cell-enriched cultures.

Sertoli cell-enriched preparations from testes of 20-day-old rats were cultured in a defined medium in the presence and absence of FSH or dibutyryl cyclic AMP (dcAMP). Androgen-binding activity was assayed in the culture medium, and related to testicular androgen-binding protein (ABP). The production and secretion of ABP by the Sertoli cell-enriched preparation was increased after FSH or dcAMP treatment of the primary culture. It is concluded that ABP is produced by Sertoli cells. The possibility of involvement of other cell types in the testis in ABP production is discussed.

Androgens↗
PubMed1975

Androgen-binding proteins in human benign prostatic hypertrophy.

Prostatic samples were surgically removed from 7 patients suffering from benign prostatic hypertrophy. High-speed supernatants (cytosol) containing 20-25 mg of protein/ml were prepared. Glycerol gradient ultracentrifugations were performed, using cytosol labeled at 0 C with 2-5 nM 3H-17beta-hydroxy-androstan-3-one (androstanolone or dihydrotestosterone) alone, or in the presence of 50-250-fold excess of androstanolone, estradiol, or androstane-3alpha, 17beta-diol (androstanediol). Two high-affinity saturable binding components were observed. One binding component was the androgen receptor. Its sedimentation coefficient was 8 S in low-salt medium. It had a high affinity for androstanolone. The binding of 3H-androstanolone was strongly completed by androstanolone itself, less by estradiol, and not by androstanediol. In one case, endogenous androstanolone found in the 8 S region of glycerol gradients was measured by radioimmunoassay, and it was calculated that more than 90% of the cytosol receptor binding sites might be occupied by this steroid while the total binding capacity of the 8 S receptor was estimated to approximate 2.6 pmol of androstanolone/g of prostate. No testosterone was found in the receptor fraction. The second binding component was attributable, at least in part, to the sex steroid-binding plasma protein (SBP), as indicated by its sedimentation coefficient (congruent to 4 S in low salt medium), its high affinity for androstanolone and androstanediol and its lower affinity for estradiol, and finally, its migration on polyacrylamide gel electrophoresis. In one instance, the concentration of the SBP-like protein in prostate cytosol was measured by equilibrium dialysis, and it was calculated that the binding capacity of the prostate SBP-like component corresponded to 4 pmol of androstanolone/g of prostate, a small (less than 5%) value with regard to SBP concentration in the plasma of the same patient. The blood contamination of the cytosol, as obtained from the measurement of hemoglobin, did not account for the amount of SBP found in the prostate sample. Since SBP-like protein is probably of plasma origin, to determine whether SBP was located in the extracellular space or inside the prostate cells, BPH slices from another patient were incubated in the presence of 3H-testosterone, the cytosol was prepared, and was fractionated by Sephadex G-150 column chromatography. The androstanolone/testosterone ratio in the receptor-containing peak was high (1.7), whereas in the incubation medium it was very low (0.08). In the peak containing the SBP-like protein, the ratio was 0.74, which may suggest that all or part had been exposed to the predominant androstanolone environment inside the prostatic cell.

Aged↗
PubMed1976

Biochemical actions of follice-stimulating hormone in the sertoli cell of the rat testis.

The sequenc of biochemical events associated with the action of follicle-stimulating hormone (FSH) in the testis has been investigated using a Sertoli cell-enriched testis model system. The Sertoli cell-encriched testis, created by irradiation of male rats in utero, is devoid of germinal elements but contains a normal complement of supportive Sertoli cells. Comparison of the Sertoli cell-enriched testis with normal testis, demonstrates that the two types of testes contain equal numbers of FSH specific receptors, judged by the binding of labeled hormone. In addition, FSH over a concentration range from 6 X 10(-11) to 6 X 10(-9)M will stimulate the production of adenosine 3',5' monophosphate (cAMP) in the Sertoli cell-enriched testis in a manner indistinguishable from that of the normal testis. Incubation of Sertoli cell enriched testis also results in the activation of soluble cAMP-dependent protein kinase. This response to FSH is dependent upon the age of the animal and disappears at about 32 days of age. While sensitivity to the hormone can still be detected in mature Sertoli cell-enriched animals by the addition of the phosphodiesterase inhibitor 1-methyl-3-isobutyl-xanthine, no detectable increase in phosphodiesterase activity is apparent after 30 days of age. Injection of FSH into Sertoli cell-enriched animals results in an increase in total testicular protein synthesis as well as in the production of the Sertoli cell-specific protein, androgen-binding protein within 30 minutes. Furthermore, while hypophysectomy of Sertoli cell-enriched animals result in a decline of the testicular concentration of androgen-binding protein, the injection of FSH will stimulate and maintain the levels of androgen-binding protein in such animals. These results demonstrate that the Sertoli cell-enriched testis is capable of carrying out the sequence of biochemical events previously described for FSH in the normal testis and therefore, suggest that the Sertoli cell is the primary target cell for FSH action.

Age Factors↗
PubMed1979

Hypoandrogenism and abnormal regulation of gonadotropin secretion in rats fed a low protein diet.

The function of the hypothalamic-pituitary-testicular axis was evaluated in rats fed a low protein diet for 4 weeks beginning at 21 days of age. Compared to control, the low protein group had decreased seminal vesicle and prostate weights as well as decreased testicular testosterone output in vitro, although serum testosterone was not different. The low protein group showed no consistent alterations in serum LH (basal, post-LHRH, and postcastration) compared to control although serum FSH (basal and post-LHRH) was lower in the low protein group. Despite this lower basal FSH, the low protein group had supranormal serum FSH after castration. Seminiferous tubule diameter and testicular histology were normal in the low protein group although testicular androgen-binding protein was absent. Testicular androgen-binding protein was also undetectable in a modestly food-restricted control group which had normal testicular size, testicular histology, androgen output, and serum FSH. This finding suggests that loss of testicular androgen-binding protein may be a sensitive sign of undernutrition. We conclude that rats fed a low protein diet have hypoandrogenism, normal testicular histology, and supranormal FSH after castration despite subnormal basal FSH. The latter combination suggests overproduction of an FSH inhibitor of testicular origin.

Androgens↗
PubMed1975

Changes in 5alpha- dihydrotestosterone binding to epididymal cytosol during sexual maturation in rabbits: correlation with morphological changes in the testis and epididymis.

We previously demonstrated that the caput epididymis of intact sexually mature rabbits contains a specific high-affinity binding protein for 5alpha-dihydrotestosterone (5alphaDHT). The other anatomical segments (corpus and cauda) of the epididymes of these animals had no detectable 5alphaDHT-binding activity. We have further shown that this binding was due to an androgen-binding protein of testicular origin. In the present study we have investigated 5alphaDHT binding to epididymal cytosol from sexually immature rabbits (20-104 days old). Using sucrose gradient ultracentrifugation, we have detected a unique pattern of binding. The pattern correlated well with testicular and epididymal maturation, but there was little correlation with chronological age or body weight. In the most immature animals (Group I) the seminiferous tubules appeared as solid cords and the epithelium of the ductus epididymis detectable 5alphaDHT-binding activity. In the second group (Group II), there was 5alphaDHT-binding to all three segments. The seminiferous tubules of these rabbits exhibited spermatogenic activity and lumen formation. The height of the epididymal epithelium had increased uniformly throughout the duct. The third group (Group III) had 5alphaDHT-binding only in caput cytosol. Spermatogenesis had progressed to the formation of elongated spermatids in the most immature animals of this group to the release of spermatozoa in the most mature ones. The caput epithelium of this last group of rabbits was fully differentiated. Unilateral orchidectomy of Group II rabbits resulted in a decrease in [3H]5alphaDHT-binding activity on the operated side as compared to the contralateral non-operated control side, suggesting the testicular origin of the binding protein. The failure of cyproterone or cyproterone acetate to inhibit [3H]5alphaDHT-binding to the protein, the lack of effect of N-ethylmaleimide on binding, and the rapid dissociation rate of the [3H]5alphaDHT-binding protein complex suggested that the binding moiety was testicular androgen-binding protein (ABP).

Aging↗
PubMed1975

Regulation of seminiferous tubular function by FSH and androgen.

Seminiferous tubules contain a cytoplasmic androgen receptor similar to the receptors in the epididymis and ventral prostate. The presence of a cytoplasmic receptor indicates that androgens maintain spermatogenesis by a direct action on certain types of cells within the seminiferous tubule. The Sertoli cell appears to be one of the cell types containing androgen receptors and the receptor might also be present in spermatogonia, primary spermatocytes, or peritubular cells. The Sertoli cell is stimulated by FSH to produce an androgen-binding protein which may serve to increase the accumulation of androgen in the seminiferous epithelium and make it available for binding by intracellular androgen receptors. This may be a way in which FSH enhances the action of androgen on spermatogenesis. Androgens act on the Sertoli cell to increase its response to FSH. This action of androgens on the Sertoli cell results in increased production of androgen-binding protein and may enhance the production of other substances which exert trophic effects on spermatogenesis.

Androgens↗
PubMed1976

Effect of cyproterone acetate on androgen-dependent synthesis of alpha2u globulin in rats.

Cyproterone acetate (CA, 2-5 mg/100 g body wt) inhibited androgenic induction of alpha2u globulin in spayed rats. In mature male rats, which normally produce alpha2u globulin, ten daily injections of CA did not inhibit synthesis of this protein. Long-term treatment of mature male rats (two injections every week for 12 weeks) showed only slight inhibition of alpha2u synthesis after 10 weeks of CA treatment. CA also failed to compete with 5alpha-dihydrotestosterone for the cytosol androgen-binding protein of male rat liver. The inhibitory effect of CA on the primary induction of alpha2u globulin in the spayed rat and its lack of effect on continued synthesis of this protein in maximally induced mature male rats are consistent with the hypothesis of a two-step mechanism for androgenic regulation of alpha2u synthesis, an initial CA-sensitive step followed later by a CA-insensitive step.

Alpha-Globulins↗
PubMed1975

Some properties of androgen-binding activity in rat testis.

High-affinity (Ka approximately equal to 5 X 10(8) M-1 for testosterone) androgen-binding activity in rat testis was shown to have a rapid dissociation rate constant (t1/2 = 3 min, 0 degrees C, 30% glycerol buffer) using dextran-coated charcoal to separate bound from free hormone. Because of this fact, exchange of endogenous and labeled hormone was complete in the assay incubation time (16 h, 0 degrees C) and Scatchard plots of the high-affinity binding data were shown to measure total as contrasted to available sites. The binding was highly specific for androgens. Polyacrylamide gel electrophoresis separated high-affinity androgen-binding protein (Rf 0.54) from albumin (Rf 0.62). Binding site estimates under saturating conditions or by Scatchard analysis of electrophoresis data utilizing [3H]dihydrotestosterone agreed reasonably well with estimates made by the charcoal technique using [3H]testosterone.

Animals↗
PubMedDate not supplied

Impaired Sertoli cell function in experimental cryptorchidism in the rat.

The production of testicular androgen-binding protein (ABP), as a measure of Sertoli cell function, was studied after unilateral or bilateral experimental cryptorchidism in adult rats. Two or 4 weeks after the testis had been translocated to the abdomen, no major changes were found in the concentration of ABP per mg protein, although there was a marked and progressive decrease in ABP content per testis. However, the rate of ABP production was greatly decreased, as measured by the accumulation of ABP during 16-h ligation of the efferent ducts or by the production of ABP by testis mince in an in vitro system. This indicates that the Sertoli cell function is severly impaired by the intra-abdominal position.

Animals↗
PubMed1976

Further characterization of the androgen receptor in rat testis.

Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules.

Animals↗
PubMed1975

Demonstration and partial characterization of cytosol receptors for testosterone.

Androgen uptake was investigated in several peripheral organs after administration of (1,2,6,7 minus -3H)testosterone to castrated male rats. The animals were killed after 30 min, the organs were taken out, and the radioactivity was determined after tissue combustion. A relatively high accumulation of androgen was found in pancreas, adrenals, spleen, thigh muscle, kidneys, and liver in addition to the classical androgen target organs coagulation glands, seminal vesicles, prostate, preputial glands, and harderian glands. In a second serier of experiments, nuclear and cytosol fractions were prepared from prostate, seminal vesicles, coagulation glands, preputial glands, spleen, submaxillary glands, kidneys, and pancreas from castrated male rats give (1,2,6,7 minus -3H)testosterone, and these fractions were then characterized by thin-layer and radio-gas chromatography with respect to their patterns of labeled steroids. Only prostate and seminal vesicles were found to contain significant amounts of nuclear 5alpha-(-3H)dihydrotestosterone. The major nuclear androgen was (-3H)testosterone that was the only detectable labeled steroid in coagulation glands, preputial glands, and spleen and that constituted 70% or more of the nuclear radioactivity in seminal vesicles, submaxillary glands, kidneys, and pancreas. These results indicate that testosterone itself may be the predominant active androgen principle in vivo in most androgen target organs and that conversion to 5alpha-dihydrotestosterone is generally not a prerequisite for androgen activity. Using an ultrasensitive micromodification of isoelectric focusing (cf. M. Katsumata and A. S. Goldman (1974), Biochem. Biophys. Acta 359, 112. It was possible to show that cytosol from kidney; submaxillary gland, thigh muscle, and levator ani muscle and nuclei from kidney and submaxillary gland contained androgen-binding proteins with pI's in the region 4.6-5.1 ("4.6 minus 5.1 Complex"). This complex also formed in vitro after incubation of (1,2,6,7 minus -3H)testosterone with cytosol from kidney and submaxillary gland. (1,2,6,7 minus -3H)Testosterone was bound with high affinity to receptor proteins in cytosol from both kidney, submaxillary gland, and thigh muscle with dissociation constants of 5.0 x 10 minus -12 M (kidney), 3.3 x 10 mi;nus -11 M and 4.1 x 10 minus -10 M (two types of binding sites, submaxillary gland), 2.4 x 10 minus -12 M (thigh muscle) and 1.9 x 10 minus -12 M (levator ani muscle). The number of binding sites was in all cases between 1 and 20 fmol/mg of protein. On the basis of these results the hypothesis is presented that a common class of testosterone receptors is present in most organs and that these receptors can be detected both in vivo and in vitro provided methods sensitive enough are utilized.

Animals↗
PubMed1976

Dihydrotestosterone binding by cultured human fibroblasts. Comparison of cells from control subjects and from patients with hereditary male pseudohermaphroditism due to androgen resistance.

Dihydrotestosterone binding was measured in culture fibroblasts from 14 control subjects and from 12 patients with five different types of hereditary male pseudohermaphroditism. Two assays of binding were used--an intact monolayer assay and density gradient centrifugation of cell extracts. In the intact monolayer assay of normal cells the uptake of [3H]dihydrotestosterone consisted of two components. The first was a high affinity component that exhibited saturation at approximately 1 nM dihydrotestosterone. The second was a low affinity component that was not saturable with concentrations of steroid up to 5 nM. Twice the number of high affinity binding sites were present in fibroblasts grown from genital skin (foreskin, labia majora, and scrotum) as from nongenital sites (37 vs. 14 fmol/mg protein). In the density gradient assay in 5-10% sucrose, the major peak of dihydrotestosterone binding was in the 8S region in low molarity buffer and in the 4S region in 0.5 M KCl. High affinity binding was normal in cells from two patients with familial incomplete male pseudohermaphroditism, type 2, an autosomal recessive defect in which dihydrotestosterone formation is deficient, and in cells from a patient with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency, an autosomal recessive defect of testosterone synthesis. High affinity binding was low by both methods in fibroblasts from five patients with complete testicular feminization. Furthermore, binding by both methods was also low in cells from three subjects with familial incomplete male pseudohermaphroditism, type 1, a presumed X-linked recessive disorder of androgen resistance, and in fibroblasts grown from a subject with the incomplete form of testicular feminization. The finding that dihydrotestosterone binding is abnormal in two forms of hereditary androgen resistance in addition to complete testicular feminization suggests either that these disorders are the result of allelic mutations affecting the function of the androgen-binding protein or that normal dihydrotestosterone binding requires the participation of more than one gene product.

Binding Sites↗
PubMed1979

[The determination, secretion and plasma concentration of androgens].

The present state of modern methods for the determination and some data for secretion and plasma levels of the principal circulating androgens (testosterone, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, androstenedione and dehydroepiandrosterone) in men and women under normal and pathological conditions are described.

Adolescent↗