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PubMed1975

LH-hCG receptors and testosterone content during differentiation of the testis in the rabbit embryo.

The development of gonadotropin receptors for LH and hCG in the fetal rabbit testis from 17-29 days of gestation was followed by quantitative binding studies with [125I]iodohCG and compared with gonadal testosterone content and the histological differentiation of the fetal Leydig cells. The concentrations of gonadotropin receptors and testosterone in the fetal testis were low on days 17 and 18 and increased strikingly on day 19. This time sequence for development of LH-hCG receptors and steroid content of the testis was correlated exactly with the histological appearance of the endoplasmic reticulum characteristic of the differentiated Leydig cell. When fetal testes were examined at 12-h intervals between days 17 and 19, gonadotropin binding and testosterone content were closely correlated at all times studied. Thus, no dissociation between the two functions was demonstrable in the testis at any time during gestation. In the fetal ovary, LH-hCG binding and testosterone content were low or undetectable at all stages of gestation. These observations demonstrate a close temporal relationship between the appearance of the LH-hCG receptor and the synthesis of testosterone by the fetal testis and demonstrate that the histological and functional differentiation of the Leydig cell occurs within a few hours at approximately day 18 of gestation. The simultaneous appearance of LH-hCG receptors and testosterone synthesis in the gonad can be regarded as the biochemical manifestations of Leydig cell differentiation in the testis of the fetal rabbit.

Aging↗

PubMed1975

Further studies on the effect of cyclic nucleotides on testis DNA synthesis.

The inhibitory effect of dibutyryl cyclic AMP (dbcAPM) on in vitro rat testis DNA synthesis appears to be relatively specific in nature. Of 7 organs studied, only testis and kidney in vitro DNA synthesis was significantly affected. In addition, another cyclic nucleotide, dibutyryl cyclic GMP (by dbc AMP), had no effect on in vitro testis DNA synthesis. This was true whether testis tissue was mature or immature. Similarly, by dbcAMP had no significant effect on in vitro testicular protein or RNA synthesis. The inhibition of in vitro testicular DNA synthesis by dbcAMP occurs while 3H-cAMP is accumulating in testis tissue. dbcGMP was found to have no antagonistic effect towards the inhibitory effect of dbcAMP on in vitro testis DNA synthesis.

Aging↗

PubMed1976

Torsion of the testis and allied conditions.

In 15 years at Bristol there have been 293 cases of torsion of the testis, 55 cases of torsion of a testicular appendage and 5 cases of testicular ischaemia due to other causes. The risk of a male developing torsion of the testis or its appendix by the age of 25 is about 1 in 160. Both conditions occurred primarily in adolescents, but among prepubertal boys torsion of an appendage was as common as torsion of a normally descended testis. There was a slight left-sided preponderance in testicular torsion, more marked in torsion of the appendages; the incidence of bilateral torsion was 2-0 and 1-8 per cent respectively. The clinical features and differential diagnosis of the two conditions are compared. Torsion of a testicular appendage is the most commonly misdiagnosed scrotal lesion, the preoperative diagnosis being correct in only 11 per cent of cases compared with 90 per cent for torsion of the testis. Twenty-one cases of recurrent torsion underwent prophylactic bilateral orchidopexy. There were 20 cases of torsion of undescended testes, with a salvage rate of only 20 per cent. The overall testicular survival rate was 55-3 per cent. Viability depends upon the possibility of spontaneous reduction, the preoperative delay after the onset of symptoms, the degree of torsion of the cord and the length of follow-up in doubtful cases. Urgent scrotal exploration is advised in every case of acute testicular pain unless there is overwhelming evidence of epididymoorchitis. Exploration of the opposite side is mandatory in torsion of the testis and advisable in torsion of an appendage.

Adolescent↗

PubMed1977

Biological damage in testis by iodine-125 in partially blocked thyroid of rats.

Degeneration of testis has been observed after administration of Iodine-125 in potassiumperchlorate treated rats. Histological damage is associated with loss of DNA, RNA, acid phosphatase, total adenosine triphosphatase (ATPase) and Na/K dependent ATPase. Iodine-125 induced atrophic testis shows higher content of sodium and lower levels of potassium as compared to control testis. Damage of testis by Iodine-125 has been compared with atrophied testis, following gamma irradiation earlier reported. Auger effect due to Iodine-125 decay and transmutation at the sites of nuclei and plasma membrane of germinal cells seems to be the possible explanation for testicular damage caused by Iodine-125.

Acid Phosphatase↗

PubMed1975

Androgen receptor in nuclei of rat testis.

Testis nuclei of hypophysectomized rats selectively accumulate labeled testosterone and 5alpha-dihydrotestosterone following the injection of tritiated testosterone in vivo. Testosterone and 5alpha-dihydrotestosterone are bound to macromolecules in nuclei and can be extracted with 0.5 M KCl. Accumulation of protein bound radioactive androgens in nuclei of isolated seminiferous tubules is similar to that of whole testis. The relative amounts of testosterone and dihydrotestosterone in purified nuclei were similar to the relative amounts bound to cytoplasmic receptors, suggesting that cytoplasmic androgen-receptor complexes may be transported into the nuclei. Binding of labeled androgen is saturable and inhibited by prior injection of unlabeled testosterone or cyproterone acetate. Nuclear binding sites are destroyed by the proteolytic enzyme pronase, but not by DNase. Like the cytoplasmic androgen-receptor complexes in rat testis, nuclear androgen-protein complexes are heat labile and dissociate slowly at 0 degrees C. androgens fail to accumulate in testis nuclei of the Stanley-Gumbreck androgen insensitive rat, a species lacking cytoplasmic androgen receptors in testis and other androgen target tissues.

Animals↗

PubMed1978

Binding of bovine thyrotropin to receptors in rat testis and its interaction with gonadotropins.

Previously, we have shown that preparations of hCG bind to bovine thyroid membranes, as judged from their ability both to inhibit the binding of 125I-labeled bovine TSH (bTSH) and to activate adenylate cyclase (Amir, S.M., H. Uchimura, and S.H. Ingbar, J Clin Endocrinol Metab 45: 280, 1977). In the present studies, 125I-labeled, highly purified bTSH ([125I]bTSH) has been shown to bind specifically and saturably to receptors in a particulate fraction from rat testis. At 37 C, binding was rapid, reaching a maximum level in less than 15 min, but then declining markedly during the next several hours. At 22 C, binding reached a steady state after 2 h and remained unchanged for another 22 h. Binding of [125I]bTSH was greatest at pH 5.5, at which pH more than 50% of [125I]bTSH was bound in the presence of 330 microgram/ml particulate protein, the concentration of protein that yielded maximum binding. Nevertheless, the majority of experiments were conducted at lesser protein concentrations and at physiological pH (7.45), under which conditions total binding was only 25% of that measured at pH 5.5. Scatchard plots indicated the presence of a single binding site with a dissociation constant of 5.8 X 10(-8) M and a binding capacity of 0.22 nmol/mg protein on the basis of data obtained at 22 C and pH 7.45. Both crude and highly purified preparations of hCG inhibited the binding of [125I]bTSH to testis particulate fraction; crude hCG had 46 times the activity, and purified hCG had only one-tenth the activity of bTSH itself in this respect. This was true despite the fact that with respect to the displacement of [125I]hCG, crude and purified hCG were almost equally active. Bovine LH had one-third the activity of bTSH in displacing [125I]bTSH. Human FSH inhibited [125I]bTSH binding only slightly at the highest concentration tested, while glucagon, insulin, PRL, and GH were inactive. Purified bTSH inhibited the binding of [125I]hCG to testis particulate fraction but contained only about 2% of the activity of purified hCG. Lineweaver-Burk analysis suggested that inhibition of [125I]hCG binding by bTSH was competitive in nature. Purified bTSH stimulated cAMP production in Leydig cells, but with only about 0.1% of the activity of purified hCG. It is concluded that bTSH binds reversibly, saturably, and with relatively high affinity to receptors in rat testis that are either the same as receptors for hCG and LH or that interact therewith. bTSH, like hCG, is capable of stimulating the production of cAMP in rat Leydig cells, but is much less potent than hCG in this regard. Preparations of crude hCG contain a factor lacking hCG activity in bioassay, immunoassay, and receptor assay that is especially potent in displacing [125I]bTSH from receptors in testis, as has earlier been described for bTSH receptors in bovine thyroid membranes.

Animals↗

PubMed1975

Changes in nuclear proteins of rat testis cells separated by velocity sedimentation.

The technique of velocity sedimentation at unit gravity has been used to separate rat testis cell suspensions into fractions enriched in particular cell types. Changes in the nuclear proteins from the various fractions have been characterized by polyacrylamide gel electrophoresis, and correlated with the changing morphology of the nucleus during spermatogenesis. The most striking alterations in both protein composition and nuclear morphology occur during spermatid maturation as both histone and non-histone proteins are replaced by highly basic, low molecular weight, spermatidal proteins. This replacement process is accompanied by a quantitative reduction in both histone and non-histone proteins. The synthesis of at least three basic proteins has been identified with late stage spermatids. One of these proteins is a highly basic sperm-specific protein containing high levels of cyst(e)ine and arginine. A second protein synthesized in late stage spermatids is lysine rich, while the third protein contains cyst(e)ine and co-migrates with histone F2a1 on acid-urea polyacrylamide gels. The changes in protein composition of rat testis nuclei after irradiation or hypophysectomy reflect the resulting changes in the cellular composition of the testis. After selective elimination of the germinal cells by irradiation, the electrophoretic pattern of acid-soluble proteins from the testis is very similar to that of somatic tissue. Thus, the cellular specificity of nuclear proteins demonstrated here using cell separation techniques is also apparent following treatments which selectively alter the cellular composition of the testis.

Amino Acids↗

PubMed1975

[New views on the significance and treatment of undescended testis (author's transl)].

Undescended testis is of clinical importance because there are increased risks of milignancy and torsion and disturbances of fertility and psychosexual development. New quantitative morphologic investigations show that human prepubertal testicular maturation does not occur in phases but is continuous. This made it necessary to investigate afresh the causes of disturbance of fertility and the treatment of indescended testis. Our own investigations show that damage to the germ epithelium need not be congenital but may develop because of its ectopy. If, in dogs, a testis is placed into the abdomen, not only this but also the normally placed testis in the scrotum is damaged. The diameter of the tubules and their surfaces as well as the numbers of pachtenous primary spermatocytes are significantly reduced both in the displaced and the normally placed testis. Nuclear surfaces and density of the cells involved in spermatogenesis differ from those in the controls. The findings support the plea for early hormonal or surgical treatment in order to prevent later disturbances of fertility.

Age Factors↗

PubMed1976

[Surgical technique in the management of undescenced testis (author's transl)].

In cases of retentio abdominalis or inguinalis and of ectopic testis, surgery is performed about the 2nd year of life. Essentials of the operating technique are: incision of the skin must not be parallel to the spermatic cord; testes and spermatic cord must be mobilized without trauma; ideally a biopsy of the testis should be taken; any pulling of the spermatic cord and torsion of it during fixation of the testis should be avoided. If initial tensionfree placement of the testis in the scrotum is impossible, the operation should be carried out in 2 sessions with an interval of 6-12 months. In 241 cases of children operated on from 1972-1975 with 308 total operations, the author observed 2 recurrences and 1 deep infection (scrotal abscess).

Adolescent↗

PubMed1975

Studies on the human testis. VI. NADH-linked reactions of microsomal steroid 20alpha-and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase.

NADH-linked 20alpha- and 20beta-hydroxysteroid dehydrogenase and 17alpha-hydroxylase activities were demonstrated in the microsomal fraction of the human testis. The microsomal 20alpha-hydroxysteroid dehydrogenase showed substrate affinity to pregnenolone and progesterone and not to 17alpha-hydroxyprogesterone and preferred NADH to NADPH as a hydrogen donor. In the presence of NADH, the optimal pH for the enzyme was 7.7 and the apparent Michaelis constants of the enzyme for progesterone and pregnenolone at 37 C and pH 7.4 were 6.9-7.1 X 10-6M and in the order of 10-5M, respectively, 17alpha, 20beta-Dihydroxypregn-4-en-3-one was the only significant metabolite produced from 17alpha-hydroxyprogesterone by microsomal fraction of the human testis in the presence of NADH. The apparent Michaelis constant of microsomal 20beta-hydroxysteroid dehydrogenase for 17alpha-hydroxyprogesterone in the presence of NADH was in the order of 10-5M at 37 C and pH 7.4. The microsomal 17alpha-hydroxylase catalyzed the metabolism of pregnenolone and progesterone at a similar rate in the presence of NADH. The optimal pH and the apparent Michaelis constant at 37 C and pH 7.4 of the NADH-linked reaction of 17alpha-hydroxylase for progesterone were 7.7 and 5.3-5.4 X 10-7M, resepctively. The NADH-linked enzyme activity for progesterone was competitively inhibited by both pregn-5-ene-3beta, 20alpha-diol (inhibition constant: 1.7 X 10-7M) and 20alpha-hydroxypregn-4-en-3 one (inhibition constant: 6.6 X 10-7M), and was resistant to poor oxygen supply during incubation. The results indicate that the microsomal 20alpha-hydroxysteroid dehydrogenase is a different enzyme from the one in the soluble fraction of the human testis and that microsomal 17alpha-hydroxylase in the human testis is activated by NADH as well as NADPH.

Binding, Competitive↗

PubMed1977

[Long-term study on the influence of running exercise, food restriction, running exercise + food restriction and of parenterally applicated testis cells on age-parameters of the rat (author's transl)].

Preliminary results of a long-term study on 1100 male Sprague-Dawley rats are presented, showing the influence of running exercise, of restricted diet, of both of these together and of the s.c. application of lypholized testis cells. Up to now animals aged 9, 15 and 24 mths were investigated. The test-animals were exposed to the experimental conditions from their 6th month of life. The running exercise was carried out on a treadmill (30 m at a speed of 25 m/min, horizontal) 5 days a week. A food restriction of about 20% was achieved by 2 fasting-days a week. The lyophilized testis cells were injected for the first time at an age of 9 mths and afterwards in 6 mths intervals. Between the injection and the assessment of the age-parameters there was an interval of 6 mths. S o fare the following parameters of the comprehensive test-program have been evaluated: 1) running performance in m (treadmill, 20 m/min, ascent 15 degrees), 2) motor activity (Animex Activity Meter), 3) chemical contraction-relaxation of tail-tendon-fibers, 4) total lipids and total cholesterol in the plasma. The results obtained so far show that a mild regular training, moderate food restriction and the s.c. application of testis-cells are able to cause a significant shift in the dirction of a younger biological age in at least some of the age parameters. The action of the testis-cells seems to affect most of the age parameters but shows the tendency to be more distinct at a higher age. More concrete statements about the influence on the biological age or the vitality will only be possible after the multivariate analysis of the results.

Age Factors↗

PubMed1979

Agenesis or atrophy of the testis and vas deferens.

In this study the author examines the relationship between agenesis or atrophy of the testis and of the vas deferens. From a prospective study of 237 cases of unilateral and bilateral undescended testis, 12 cases of agenesis of a testis were seen; 9 of the 12 cases were associated with agenesis of the vas deferens and in 3 of these unilateral renal agenesis was also present, not necessarily ipsilaterally. Three other cases of testicular agenesis and four cases of extreme testicular atrophy were seen. In all seven, the vas deferens was present in part or in its entirety and roentgenography disclosed a normal upper urinary tract. Agenesis of the vas deferens was seen only in patients with monorchism. No patient was anorchid. It is concluded that an important link exists between agenesis of the vas deferens and agenesis of the testis.

Abnormalities, Multiple↗

PubMed1978

Primary carcinoid tumor of the testis: case report, ultrastructure and review of the literature.

A case of primary pure carcinoid tumor of the testis which occurred in a 71-year-old male is reported. The patient was treated by radical orchiectomy and remains well and symptom free 10 months after operation. Histologically as well as ultrastructurally the tumor showed typical appearances of carcinoid tumor of midgut derivation. 23 cases of carcinoid tumors of the testis were discovered in the literature. Of these 17 were primary testicular carcinoids, and 6 were metastatic to the testis. Of the 17 cases of primary carcinoid tumors, 14 were pure carcinoids and only 3 were associated with teratoma. None of the primary testicular carcinoids were associated with metastases and the prognosis after orchiectomy was excellent, thus indicating that no further therapy is necessary. The prognosis of patients with carcinoid metastatic to the testis is poor. In view of this it is very important to determine whether the tumor is primary or metastatic.

Aged↗

PubMed1979

Interstitial cell carcinomas of the testis in Balb/C male mice ingesting methoxychlor.

Balb/c and C3H strains male and female mice ingested 750 ppm methoxychlor or 100 ppm DDT in the diet for 2 years. Balb/c strain male mice ingesting methoxychlor developed a highly significant incidence of interstitial cell carcinomas of the testis. Balb/c strain male mice ingesting DDT and C3H strain male mice receiving methoxychlor or DDT did not have testicular tumors. The carcinomas of the testis varied from well-differentiated to poorly differentiated and undifferentiated and were capable of metastasis. Carcinomas of the testis have been described in Balb/c strain male mice, but not C3H, given estrogens. The carcinogenicity for testis of Balb/c strain male mice is most likely related to the estrogenic activity of methoxychlor.

Animals↗

PubMed1976

Two rare cases of ectopic testis.

A case of pubopenile testis and a case of perineal ectopic testis are presented. The mechanism of descensus is largely positive, possibly facilitated by raised intra-abdominal pressure. The testis is usually guided by the gubernaculum and ectopia results from gubernacular failure. The ectopic testis is relatively rare but is easily recognized and treated by orchiopexy.

Child, Preschool↗

PubMed1975

[Endocrine and morphological investigation in undescended testis (author's transl)].

Determination of the basal and LH-RH-stimulated luteinizing hormone (LH) levels as well as testicular morphology in patients with surgically treated (n equals 112) and non-treated (n equal 96) undescended testes gave the following results: Unilateral of bilateral undescended testes are probably a form of primary, secondary or tertiary hypogonadism. In a high percentage abnormal basal and stimulated serum-LH values can be demonstrated. The testosterone values are within normal limits. The gonadal tissue damage in the abnormally situated testes of prepubertal boys seem to be congenital. With increasing duration of the malposition, particularly after the onset of puberty, a secondary tissue degeneration in the dystopic testis occurs. The damaging influence on the testicular tissue caused by the abnormal position seems to take place mostly at the end of prepuberty. A decrease in the number of spermatogonia in the tubuli of dystopic testes during the first 2 years of life is physiological. A surgical repositioning of the dystopic testis into the scrotum within the first 2 years of life is not indicated. Damage of gonadal tissue in the scrotal testis caused by the dystopic testis in unilateral maldescent could not be demonstrated. The optimal space for orchidopexy is between the third and fifth year of life.

Adolescent↗

PubMed1976

Cryptorchidism, hernia, and cancer of the testis.

Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia.

Cryptorchidism↗

PubMed1979

Characterization of estrogen binding in the developing rat testis. Ontogeny of the testicular cytoplasmic estrogen receptor.

The properties and physical characteristics of a steroid binding component present in the immature (7 to 35 day) rat were investigated and found to be different from those of the 17 beta-estradiol receptor in the mature rat testis. These properties include a binding capacity of 483 fmol estradiol/mg protein, a Ka at equilibrium of 4.23 x 10(7)M-1, and broad steroid specificity as shown by interaction with several steroids; no binding was observed with diethylstilbestrol. The component, found in blood and several tissues including the testis, migrated as a 4.6S peak on sucrose gradients. This 4.6S component, which interacted with an anti-alphafetoprotein antiserum, decreased with age and was not detectable in the testis after day 21 or in the serum after day 25. These data suggest that this component is alphafetoprotein. Ontogenic appearance of the testicular cytoplasmic 17 beta-estradiol receptor in the developing rat was further elucidated. Sucrose gradient sedimentation analysis of cytosols revealed an 8S binding component that was first detectable at 23 days. Specific binding (fmol [3H]-estradiol/testis) was relatively low in neonates, rose to 59 fmol during the third week, and increased dramatically to 333 fmol at 7 weeks; binding rose only gradually after maturity. The receptor was tissue specific and steroid specificity studies demonstrated that only diethylstilbestrol and other estrogens were effective in competing with 17 beta-estradiol for binding sites. The Ka at equilibrium was determined as 3 x 10(10)M-1 and the binding sites were saturable in an in vitro system. The receptor did not interact with anti-alphafetoprotein antiserum as indicated by sucrose gradient studies. These data demonstrate the developmental appearance of the testicular cytoplasmic estradiol receptor in the immature rat.

Aging↗