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PubMed2004

The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis.

The metallopeptidase angiotensin-converting enzyme (ACE) plays a pivotal role in the cardiovascular system by generating the vasoconstrictor peptide angiotensin II. A homolog of ACE with different substrate specificity, ACE2, has recently been cloned that shows an expression pattern restricted to endothelial cells of the heart and kidney, epithelial cells of the distal tubule of the kidney, and the testis. Although the importance of ACE2 to cardiac function is already evident, its role in the testis remains unknown. In this study, we report the cloning and expression of human testicular ACE2 and confirm that it is identical to the somatic form of the enzyme. ACE2 catalytic activity was present in membrane preparations of whole testes and Leydig cells from adult rats; expression of the protein in Leydig cells was confirmed by Western immunoblot analysis. Using immunohistochemistry, ACE2 expression was confined to the Leydig cells in the rat testis and to Leydig and Sertoli cells in the human testis. Ablation of the Leydig cells in the rat by the specific toxin, ethane dimethane sulfonate, eliminated ACE2-positive cells from the interstitium. Expression of ACE2 in rat Leydig cells was up-regulated during the development of adult-type Leydig cells at puberty and after ethane dimethane sulfonate treatment. Expression of ACE2 activity in the testis was not significantly altered by manipulation of the pituitary-testicular hormonal axis with sc testosterone implants. These data suggest that ACE2 is a constitutive product of adult-type Leydig cells and may participate in the control of testicular function by as yet unknown mechanisms.

Angiotensin-Converting Enzyme 2↗
PubMed1985

Identification and characterization of arginine vasopressin receptors in the rat testis.

We have previously shown that arginine vasopressin (AVP) directly inhibits testicular steroidogenesis in vitro. In the present study, binding of neurohypophysial peptides to interstitial cells of the rat testis was studied using [3H]AVP as the ligand. Interstitial cells were obtained from adult rat testis after collagenase dispersion and were incubated with [3H]AVP in the presence or absence of unlabeled AVP. Binding equilibrium was reached by 60 min at 4 C, while incubation at higher temperatures (23 and 37 C) resulted in an apparent decrease in binding. Scatchard plot analysis of equilibrium binding data revealed the existence of one class of high affinity, low capacity binding sites (Kd = 1.0 +/- 0.3 nM; maximal binding = 8.5 fmol/10(6) cells). In addition, the rate constants of association and dissociation were calculated to be 0.024 nM-1 min-1 and 0.009 min-1, respectively. Addition of naturally occurring neurohypophysial hormones as well as their synthetic analogs inhibited [3H]AVP binding to testis cells, resulting in parallel displacement curves. The order of potencies for the native peptides was: AVP = lysine vasopressin = arginine vasotocin (IC50, 5 X 10(-10) M) greater than oxytocin = mesotocin (IC50, 4 X 10(-7) M) greater than isotocin = glumitocin (IC50 greater than 10(-6) M). Furthermore, two potent vasopressor antagonists, d(CH2)5Tyr(Me)AVP ([1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]AVP) and dPTyr(Me)AVP ([1-deaminopenicillamine-2-(O-methyl)tyrosine]AVP) competed for [3H]AVP binding with a higher affinity (IC50, approximately 10(-11) M) than native AVP. In contrast, a selective antidiuretic agonist, dDAVP (1-deamino-8-D-AVP), only competed weakly for receptor binding, while a specific oxytocic agonist, (Thr4,Gly7)oxytocin, did not affect AVP binding. These results suggested that the testis may contain the V1 receptor subtype. Studies on the intratesticular distribution of AVP receptors indicated minimal binding to cells derived from the seminiferous tubule, while most of the AVP-binding sites sediment with enriched fractions of Leydig cells after Metrizamide density gradient centrifugation. AVP-binding sites were also found in rat liver, kidney, and anterior pituitary (10.7, 2.6, and 1.7 fmol/mg protein), whereas adrenal, cerebellum, prostate, and hypothalamus were devoid of AVP-binding sites. Thus, we have demonstrated the presence of high affinity, stereospecific receptors for AVP in the interstitial cell compartment of the rat testis. These V1 receptors may mediate the direct inhibitory action of neurohypophysial hormones on testicular Leydig cell steroidogenesis.

Animals↗
PubMed1996

Natriuretic peptides in the human testis: evidence for a potential role of C-type natriuretic peptide in Leydig cells.

Functional studies indicate that natriuretic peptides have direct effects on Leydig cells of the testis. In this report, we demonstrate local synthesis of one member of the natriuretic peptide family, C-type natriuretic peptide (CNP), in Leydig cells of human testes. Using RT-PCR assays, messenger RNA (mRNA) for the CNP precursor was detected in human testis and found to be prominently expressed in Leydig cells. Immunohistochemical analyses revealed CNP to be almost exclusively associated with Leydig cells. Distinct differences in the staining intensity-including cells without detectable staining-suggest a heterogeneity of CNP expression within the Leydig cells. Moreover, the presence of transcripts for the CNP receptor, a particulate guanylate cyclase, termed GC-B, was demonstrated by RT-PCR in human testis and in isolated Leydig cells. The expression of this receptor in human testis membranes could be confirmed by affinity labeling with 125I-labeled CNP. These findings demonstrate, for the first time, the production of a natriuretic peptide in human Leydig cells. The occurrence of CNP and its receptor in the human testis points to a local role of the peptide, presumably acting in an auto- or paracrine manner to modulate organ-specific functions.

Adult↗
PubMed2005

Myeloid sarcoma involving the testis.

Myeloid sarcoma is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. Myeloid sarcoma involving the testis, however, is uncommon and very rarely occurs as an isolated mass. We describe 4 patients with myeloid sarcoma involving the testis, including 2 patients in whom the neoplasm was isolated to the testis (1 unilateral and 1 bilateral). Histologically, 4 neoplasms were poorly differentiated and 1 was blastic. Each neoplasm was shown to be of myeloid lineage, and negative for T- and B-cell specific antigens using immunohistochemical methods. One case was also positive for chloroacetate esterase. In the literature, most cases of myeloid sarcoma involving the testis represent relapse or the initial presentation of acute myeloid leukemia. Including the 2 cases we report here, only 7 cases of myeloid sarcoma isolated to the testis have been reported.

Adult↗
PubMed2003

Characterization of the testis in congenitally ubiquitin carboxy-terminal hydrolase-1 (Uch-L1) defective (gad) mice.

The gracile axonal dystrophy (gad) mice are known to have a deletion within the gene encoding ubiquitin carboxy-terminal hydrolase-1 (Uch-L1) and show hereditary sensory deterioration and motor paresis. Expression of Uch-L1 is reported to be almost limited to the nervous system and testis. To understand whether Uch-L1, one of the major ubiquitin carboxy-terminal hydrolase (UCH) isozymes in the testis, affects spermatogenesis and other UCH isozymes (Uch-L3, L4 and L5) expression in the testis, we compared the testis between gad, hetero and wild type mice by histological, immunohistochemical analyses and RT-PCR. Histological analysis in 25-week-old gad mice showed shrinking of seminiferous tubules, decreasing total number of cells and enlargement of remaining cells in seminiferous tubules. By immunohistochemistry, a significant decrease (p < 0.05) in the number of proliferating cell nuclear antigen (PCNA) positive cells was observed. Expression of other UCH isozyme mRNAs was not apparently affected by Uch-L1 deficiency in 25-week-old gad mice. This study is the first report on the testis of gad mutant mouse.

Animals↗
PubMed1995

[Sclerotherapy with 3% polidocanol for hydrocele testis].

BACKGROUND: We studied the clinical efficacy of sclerotherapy with injection of 3% polidocanol for hydrocele testis. METHODS: From July, 1992 to March, 1995 sclerotherapy with single injection of polidocanol was performed for 11 patients with 12 hydrocele testis on an outpatient basis. We instilled 3 or 5ml of 3% polidocanol after complete removal of fluid in the hydrocele testis. RESULTS: Complete disappearance on ultrasonography was observed in 75% of the hydrocele testis 6 months after this sclerotherapy. There was neither pain during instillation of 3% polidocanol nor any other complication. Two patients with fluid reaccumulation underwent hydrocelectomy 16 and 6 months after sclerotherapy, respectively. CONCLUSION: This procedure seems to be a safe and useful technique as primary treatment for hydrocele testis.

Adult↗
PubMedDate not supplied

[Leydig cell tumor of the testis].

OBJECTIVE: To review our experience with Leydig cell tumor of the testis and compare our findings with those reported in the literature. METHODS: The clinical records of patients with Leydig cell tumor of the testis that were treated in our hospital were reviewed. This study analyzed patient age, reason for consultation, previous history of testicular pathology, size and location of the tumor, US pattern, histological findings, hormone analysis, semen analysis, treatment and clinical course. RESULTS: 7 patients had Leydig cell tumor of the testis, accounting for 2.1% of the testicular tumors treated in our hospital. The mean age at the time of diagnosis was 40 years. The presenting features were enlarged testis, gynecomastia, sexual dysfunction or incidental finding during testicular US assessment for cryptorchidism. Most of the tumors were hypoechoic and showed hypervascularization. Hormone analysis was abnormal in 4 patients and showed reduced testosterone and increased serum estradiol levels. The initial semen analysis showed azoospermia, severe oligozoospermia or cryptozoospermia in 4 patients. Six patients had previously undergone orchidectomy via the inguinal approach and one patient had undergone tumor resection. At 41 months mean follow-up, the tumor has been demonstrated to be benign. CONCLUSIONS: Leydig cell tumor of the testis usually presents as a testicular mass, accompanied or preceded by hormonal changes in 20% of the cases, with feminization in the adult and masculinization in the child. The lesions are always benign in children and in 90% of the adult patients. The US features are usually hypoechoic. The histological criteria for malignancy do not always correlate with the clinical features. Malignancy is established by the presence of metastasis at the time of diagnosis or during follow-up. There is currently no effective treatment for the metastasis. Following orchidectomy, the clinical hormonal manifestations return/remit in 90% of the cases.

Adult↗
PubMed2002

[Previous testicular position in boys who underwent orchidopexy due to undescended testis at the Alkmaar Medical Center, the Netherlands, during the period 1986-1999].

OBJECTIVE: To determine the previous testicular position in boys, in whom orchidopexy was performed for undescended testis. DESIGN: Retrospective, descriptive. METHOD: All boys, aged 0-18 years, who underwent orchidopexy in the Alkmaar Medical Centre, the Netherlands, during the period 1986-1999, were studied. The following information was obtained from the hospital medical records: indication for operation, date of the operation, laterality (unilateral or bilateral), the surgical findings and whether previous testicular position played a role in the decision to perform orchidopexy. For each boy who underwent orchidopexy for undescended testis, previous testicular positions up until the date of the operation were obtained from the appropriate youth health care institutions. RESULTS: Hospital records were available for 851 boys who had undergone orchidopexy. The operation for undescended testis was performed in 717 boys and previous testicular positions were obtained for 565 boys. On a per testicle basis, 707 operations were carried out (142 bilaterally, 205 left-sided, 218 right-sided). From these 707 testes, a previous intrascrotal position was found at least once in 572 (80.9%), at least twice in 493 (69.7%) and at least three times in 419 (59.3%); 135 (19.1%) testes had never been intrascrotal. The majority of previously undescended testes were operated on at 3 years of age; most operations on previously descended testes were performed at 10.5 years of age. For 344 (48.7%) out of 707 testes, previous testis localisation was known in the hospital's medical records, for 96 (13.6%) testes registration was unclear and in 267 (37.8%) testes it was not reported. In 8 (1.4%) boys, testis registration after the birth was used on referral to document previous testicular position. CONCLUSION: In total 80.9% of all orchidopexy operations were performed on testes that had previously been diagnosed as having descended normally. These probably included retractile testes as well as acquired forms. In 51.3% of the cases, previous testicular position was not known in the hospital's medical records at the time of operation.

Adolescent↗
PubMedDate not supplied

Expression and regulation of aquaporins 1, 8, and 9 in the testis, efferent ducts, and epididymis of adult rats and during postnatal development.

Aquaporins (AQPs) are membrane protein channels that allow the rapid passage of water through an epithelium containing tight junctions. In the present study, light microscope immunocytochemistry was utilized to localize several members of the AQP family in the testis, efferent ducts, and epididymis of normal adult animals during postnatal development and after various experimental procedures on adult animals. In the testis of normal adult animals, AQP-8 was expressed exclusively in Sertoli cells, while AQP-9 outlined Leydig cells. In the efferent ducts, AQP-1 was expressed on the microvilli, basolateral plasma membranes, and apical endosomes of the nonciliated cells and cilia of ciliated cells, while AQP-9 was present only on the microvilli of nonciliated cells. In the epididymis, AQP-9 was localized to the microvilli of the principal cells of all regions, with the most intense reaction being noted in the initial segment and cauda regions. The clear cells of the cauda region expressed only AQP-9. AQP-1 was not expressed in the testis or the epididymal epithelium, but it was expressed over the endothelial cells of the vascular channels of the efferent ducts and epididymis. After efferent duct ligation or orchidectomy, there was no change in the expression of AQP-1 or -9 over the microvilli or cilia of epithelial cells in the case of the efferent ducts, suggesting that testicular factors do not regulate their expression in this region. In contrast, AQP-9 expression in the principal cells of the initial segment, but not of other regions, and also in the clear cells of the cauda region was dramatically reduced after both treatments. As the expression was not restored to control levels by testosterone replacement, the data suggest that a luminal factor(s) derived from the testis regulates AQP-9 expression in the principal cells of the initial segment and in the clear cells of the cauda region. Postnatal studies revealed that the expression of AQP-1 and -9 in the different cell types of the efferent ducts and epididymis occurred between days 7 and 29, eliminating sperm and high androgen levels as possible regulating factors. Taken together, these data suggest cell specificity with respect to the expression of AQP-8 and -9 in the testis. In the efferent ducts and epididymis, specificity exists in cell, region, and tissue distribution with respect to the expression of AQP-1 and -9, and their expression does not appear to be regulated by androgens.

Age Factors↗
PubMed2003

[Impalpable testis: complete inguinal exploration by laparoscopy].

OBJECTIVE: To prospectively evaluate an inguinal approach to surgery for impalpable testis possibly assisted by laparoscopy during the same operation. MATERIAL AND METHODS: From January 1996 to March 2002 each case of unilateral impalpable testis was operated via an inguinal incision and laparoscopy was performed during the same procedure whenever the inguinal canal was devoid of any testicular structures. Sixty boys were included in this study. Anatomical features were evaluated and testes were classified according to their trophicity and their site. We evaluated the number of laparoscopies and the factors justifying this procedure. Orchidopexy was performed via an inguinal approach with extensive retroperitoneal dissection to release spermatic vessels, when necessary. A one-stage Fowler-Stephens operation was performed when the vascular pedicle remained too short despite this dissection. The results of orchidopexy were evaluated by physical examination with a minimum follow-up of 4 months. RESULTS: In this series of 60 cases, we identified 19 viable testes. Fourteen were situated in the abdomen, 3 in the inguinal canal, and 2 in a perineal ectopic position. The other cases were considered to present testicular atrophy. Laparoscopy was performed in 23 boys (38%) in whom no viable or atrophic testis was demonstrated via the inguinal incision. Sixteen of the 19 viable testes were descended by preserving the spermatic vessels with a good result. Two Fowler-Stephens operations gave a good result. One testis was removed. CONCLUSION: An inguinal incision, possibly completed by laparoscopy, appears to be a simple and reliable method of evaluation and treatment of impalpable testis.

Atrophy↗
PubMed1990

Seminoma of normally-descended and cryptorchid testis.

The records of 40 patients with seminoma of testis were reviewed; nine had cryptorchidism. The incidence of cryptorchidism among the 36 Chinese patients was 22% (8/36). All Stage I and four Stage II patients were treated by orchidectomy followed by radiotherapy of 30 Gy or more to the pelvic and para-aortic lymphatics, while another seven Stage II patients received pelvic and para-aortic lymphatics plus mediastinal irradiation. For patients with normally-descended testis, the 2-year survival for Stage I was 94% and Stage II, with small and clinically unpalpable abdominal nodal metastases, 86%. For patients with Stage I and II seminoma arising from cryptorchid testis, comparable survival can be achieved by giving similar doses of radiation and adjusting the size of the para-aortic and pelvic radiation fields to cover the known extent of the disease. The prognosis of patients with seminoma arising from cryptorchid testis depends more on the stage and extent of disease than the status of cryptorchid testis. Painful groin mass or abdominal pain were the presenting symptoms in more than half of the patients with cryptorchid testes. The changed symptomatology in this group of patients can result in diagnosis delay.

Abdominal Pain↗
PubMed1989

Torsion of the testis.

Torsion of the testis demands early diagnosis and urgent operative treatment. This study of all patients with torsion of the testis who were admitted to The Prince of Wales Children's Hospital, The Prince of Wales Hospital and The Prince Henry Hospital, Sydney, between 1965 and 1987, reinforces the need for urgent diagnosis and treatment and evaluates the diagnostic value of the sign of the contralateral horizontal testis. One hundred and thirty-one patients were studied; the majority was in the adolescent age-group. If operation were delayed beyond 24 hours without spontaneous relief of the symptoms or manipulative detorsion being performed, then at follow-up 5.5% of testes were normal; however, if operation were performed within 24 hours of the onset of symptoms, 90% of testes were normal at follow-up. In all cases in which it was sought, the sign of the contralateral horizontal testis was found, which confirms the bilaterality of the condition and that a high investment of the tunica vaginalis predisposes to torsion of the testis.

Adolescent↗
PubMed1989

[Adenocarcinoma of rete testis].

We report a case of adenocarcinoma of rete testis in 64-year-old man. His first diagnosis was hydrocele of left testis, but aspiration cytology showed malignancy. The patient underwent left orchiectomy. The pathological diagnosis was adenocarcinoma of the rete testis. The cancer was suspected to be arising from the duct of rete testis on the histological examination, and no other malignancy was found elsewhere in his body. However, he died at 10 months after the operation for lung metastasis. Adenocarcinoma of rete testis is one of the rarest malignancies. Only 25 cases have been reported since the first case was described by Feek and Hunter in 1945. This is the twenty-sixth case in the literature.

Adenocarcinoma↗
PubMed1989

[Epidermoid cyst of the testis: a report of two cases].

We report two cases of epidermoid cyst of the testis. Case 1: A 57-year-old man was admitted to Osaka University Hospital with the chief complaint of a small nodule in the left scrotal content. Physical examination revealed that a little-finger tip sized hard mass was palpable at the upper part of the left testis. Left orchiectomy was performed under the diagnosis of testicular tumor. Histological diagnosis was epidermoid cyst of the testis. Case 2: A 25-year-old man was admitted to Osaka Kosei-Nenkin Hospital with the chief complaint of a nodule in the left scrotal content. Ultrasonographic examination revealed a hypoechoic lesion with echogenic rim in the left testis. Left orchiectomy was performed under the diagnosis of testicular tumor. Histological diagnosis was epidermoid cyst of the testis. In both cases, no evidence of recurrence has been noticed.

Adult↗
PubMed1985

[Malignant lymphoma of the testis: report of two cases and review of the literature].

Two cases of malignant lymphoma arising from the testis are reported. Case 1: A 70-year-old man presented with a painless swelling of the right scrotal contents. Right radical orchiectomy was done and histological examination revealed malignant lymphoma of the testis (diffuse lymphoma, mixed type). Bipedal lymphangiography and CT scan showed metastatic lesion in the right retroperitoneal lymph-nodes. Postoperative irradiation to the inverted Y field encompassing the para-aortic, pelvic and inguinal lymph-nodes bilaterally was given to a total dose of 5,000 rad, and treatment with anti-cancer agents was subsequently started. The patient, however, died of liver failure about 6 months after the operation. Case 2: A 74-year-old man presented with painless right scrotal swelling. Right orchiectomy was performed and the tumor histologically appeared to be anaplastic seminoma. The patient received 3,000 rad of irradiation to the retroperitoneal space. There was no evidence of metastasis, until he developed swelling of the right inguinal lymph-nodes about 5 months after the operation. Afterwards, multiple skin tumors in the legs appeared. Biopsy of the skin lesions showed metastasis of malignant lymphoma (diffuse lymphoma, large cell type). The right testis removed previously was then reviewed in detail, and primary malignant lymphoma of the testis was strongly suggested. The patient responded poorly to additional irradiation or cancer chemotherapy and died about one year and 3 months after the right orchiectomy. A statistical survey was made on 117 cases of malignant lymphoma of the testis reported in Japan and the discussion is focused on the significance of new histological classification in relation to the prognosis.

Aged↗
PubMed1973

Management of the undescended testis.

Surgical correction of the undescended testis is frequently postponed beyond the optimal time, namely, 6 years of age.An accurate diagnosis of undescended testis may be made during the first year of life. Complications and mistakes arising from misdiagnosis of undescended testis and retracted testis may, therefore, be prevented by recording findings.The purpose of this article is to present the arguments in favour of early diagnosis and operative treatment of undescended testis, and to correct possible misconceptions.

Age Factors↗
PubMed1994

[Scrotal calcification associated with hydrocele testis in a child: a case report].

Scrotal calcification is a rare complication of childhood hydrocele testis. Herein, a 12-year-old boy who suffered from left hydrocele testis with intrascrotal calcification is reported. The boy had experienced scrotal pain about 6 months prior to the first visit to our hospital, and gradually noted scrotal swelling. Physical examination revealed left scrotal enlargement with transillumination. Sonographic examination revealed a left hydrocele testis, and a 1.5 cm discrete focus of calcification was found immediate cranio-lateral to the left testis, contour, size and consistency of which were palpated normally. In left hydrocelectomy, no appendix epididymidis was found. A smooth, white, spherical, firm body connecting to the head of the epididymidis was removed. A microscopic examination revealed multiple layers of collagenous tissue with the necrotic tissue in the core. We concluded that this case presented with hydrocele testis secondary to a growing calcification reacting to the infarction due to the repeated torsion of the appendix epididymidis.

Calcinosis↗
PubMed1993

Laparoscopy for the nonpalpable testis.

In boys with an impalpable testis, the gonad may be intraabdominal, canalicular, atrophic secondary to in utero torsion (vanishing), or absent. Although radiological techniques have been used to localize the testis in such patients, they are not sufficiently accurate to avoid surgical exploration. Laparoscopy provides the most rapid and accurate means of localizing impalpable testes. The technique has been demonstrated to be extremely safe. Between 40% and 75% of these boys have a vanishing testis. In the majority of the remainder of cases, the testis is intraabdominal. In boys with an intraabdominal testis, a standard orchiopexy or a one- or two-stage Fowler-Stephens orchiopexy has been used most commonly. In the two-stage Fowler-Stephens orchiopexy, the initial procedure is accomplished laparoscopically by placing a clip on the testicular vessels; the second stage is performed 6 to 12 months later as an open operation. Alternatively, if the patient is a teenager over 16 years of age or an adult, laparoscopic orchiectomy is preferable. Currently efforts are under way to develop and improve the laparoscopic-assisted orchiopexy.

Adolescent↗