E. Koh

EVIDENCE FOR THE PRESENCE OF ANDROGEN RECEPTORS IN HUMAN LEYDIG CELLS

Localization of androgen receptors (ARs) in the human testis Leydig cells was examined with an AR assay and Northern blot analysis. Leydig cells, highly purified on a Percoll gradient, were used for the experiments. AR concentration in the total cell extract containing both the cytosol and nuclear fractions in Leydig cells was measured using [3H]methyltrienolone. ARs in Leydig cells showed a high affinity for [3H]methyltrienolone and the Kd and Bmax of the receptors were 1.24 nM and 11.7 fmol/mg protein, respectively. Northern blot analysis, using a 32P-labeled full-length human AR complementary DNA (cDNA) detected a 9.5-kb hybridizing band in the total RNA extracted from Leydig cells. These data can be interpreted as evidence of the existence of ARs in human Leydig cells.

Optimal Temperature for Synthesis of DNA, RNA, and Protein by Human Testis in Vitro

To determine the optimal temperature for DNA, RNA, and protein syntheses in the human testis, the levels of incorporation of 3H-thymidine, 14C-uridine, and 14C-leucine into testicular tissue were studied at 28 degrees C, 31 degrees C, 34 degrees C, and 37 degrees C in vitro. The results suggest that the DNA synthesis is at a maximum at 31 degrees C and shows delicate temperature sensitivity, whereas the RNA and protein syntheses are at a maximum at 34 degrees C or 37 degrees C and are temperature-dependent. It is concluded that the temperature sensitivity of DNA synthesis may be one of the primary causes of delicate thermal inhibition of human spermatogenesis.

Induction of renin-angiotensin system in human testis in vivo.

To better understand the local renin-angiotensin system in Leydig cells of the human testis, the plasma renin activity (PRA) and plasma concentration of angiotensin II (PAII) in the left internal spermatic vein (ISV) and cubital vein (CV) were measured at the time of surgical repair of varicocele in 27 patients. Fourteen of the patients were given a single i.m. injection of hCG (10,000 IU/m2) 4 days before the operation, whereas the remaining 13 were not treated. Although the mean PRA or PAII levels in the CV in the treated and nontreated groups were similar, both levels in the ISV in the treated group were significantly higher than in the nontreated group (p less than 0.05). For PAII levels in the treated group, nine of 11 patients with an increased PRA level showed significantly higher levels than the normal peripheral PAII value. The serum testosterone levels in the same ISV were also much higher in the treated group than in the nontreated group (p less than 0.001). These results suggested the possibility that sex steroids might influence the renin-angiotensin system in Leydig cells.

Testicular steroids in spermatic and peripheral veins after single injection of hCG in patients with varicocele

To determine the function of Leydig cells in patients with varicocele, hCG-stimulated levels of progesterone (Prog), 17 alpha-Hydroxy-4-pregnene-3,20-dione (17OHP), 4-Androstene-3,17-dione (A-dione), testosterone (T), and estradiol-17 beta (E2) in both spermatic and peripheral veins were measured. Seventy-two patients with idiopathic varicocele were divided into four groups: patients in group 1 were untreated, whereas patients in groups 2, 3, and 4 were given a single i.m. injection of 10,000 IU hCG 24 h, 96 h, and 168 h before surgery, respectively. In the spermatic and peripheral veins, levels of Prog, 17OHP, and E2 showed peaks at 24 h, whereas levels of A-dione and T showed peaks at 96 h. Significant increases in the ratios of spermatic veins 17OHP to A-dione and 17OHP to T, and a significant decrease in the ratio of T to E2, was found 24 h following hCG treatment. These results demonstrate that, following hCG injection, there is a transient inhibition of testicular C17-20-lyase activity, probably mediated by E2, even in subfertile males with varicocele.

Bilateral Leydig Cell Tumors and Male Infertility: Case Report

A 38-year-old man with a complaint of male infertility due to azoospermia was found to have bilateral Leydig cell tumors. The tumors were synchronous, not clearly palpable and not diagnostic by ultrasonography. The serum level of estradiol was remarkably increased, and that of testosterone was above the normal upper limit. Tumors of 0.8 cm in diameter were detected by scrotal exploration, and findings of Leydig cell tumors in the bilateral testes were confirmed by histologic and electron-microscopic studies.

Testicular FSH and hCG Receptors in Sertoli-Cell-Only Syndrome

Testicular FSH and hCG receptors were measured in patients with Sertoli-cell-only syndrome (SCOS), and the value of Bmax for each hormone was compared with the value in subjects with normal testes. FSH receptor was detectable in only four of 10 patients, and the mean value of Bmax in four of the 10 patients was clearly lower than that in normal testes (p less than 0.005). On the other hand, hCG receptors were detected in all of six tested patients, and the mean value of Bmax was lower, but not remarkably so, than that in the normal testes. The function of Sertoli cells was remarkably impaired in most men with SCOS, whereas the function of Leydig cells was relatively preserved.

Extraadrenal expression of steroid 21-hydroxylase and 11β-hydroxylase by a benign testicular leydig cell tumor

We present an unusual case with bilateral testicular Leydig cell tumors displaying extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase. Histological examination of a 38-yr-old man infertile due to azoospermia showed him to have bilateral testicular Leydig cell tumors. The in vitro steroidogenic potential of the tumors and their adjacent testicular tissue was evaluated using organ culture. Tumor tissue was found to secrete deoxycorticosterone (DOC), corticosterone (B) and cortisol, which are not produced in normal adult testis, into the medium, while testicular tissue adjacent to the tumors secreted a small amount of DOC and B. Northern blot analysis with cytochrome P-450C21 complementary DNA (cDNA) and P-45011 beta cDNA as probes revealed that the tumor contained a considerable amount of mRNA for P-450C21 and P-45011 beta, while the MRNAs were not detected in the testicular tissues adjacent to the tumors. It is suggested that the high local levels of estrogen and/or progesterone within the Leydig cell tumors and their adjacent testicular tissues induced extraadrenal expression of steroid 21-hydroxylase and 11 beta-hydroxylase by the tumors and their adjacent testicular tissues.

Improvement of semen characteristics after surgical repair of bilateral testicular varicocele as compared to unilateral varicocele patients.

The operative treatment for surgical repair of bilateral testicular varicoceles was evaluated in terms of the improvement achieved in the sperm density and percentage progressive motile sperm. These parameters were compared for 27 cases of bilateral varicocele diagnosed by palpation and subjected to bilateral high ligation of the internal spermatic vein and for 40 cases of left unilateral testicular varicocele. There were no significant differences in preoperative values (such as sperm density; progressive motile sperm; serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone; and Johnsons score count) between the bilateral and unilateral testicular varicocele groups. The improvement in postoperative sperm density in the cases with bilateral testicular varicocele was apparently less satisfactory than in the cases with testicular varicocele only on the left side.

Bilateral Ureteral Stricture due to Ureteral Fibrosis

A case of bilateral ureteral fibrosis is reported. The patient, a 32-year-old man, was admitted as a result of acute renal failure. Ultrasonography showed bilateral hydronephrosis, so that in-dwelling

Testicular Macromolecular Synthesis in Men With Varicocele

The synthesis of DNA, RNA, and protein by varicocele testes with spermatogenic dysfunction was studied by examination of the levels of incorporation of [3H]thymidine, [14C]uridine, and [14C]leucine into the testicular tissue at 31 degrees C in vitro. The results suggest that DNA synthesis by the testis with moderate tubular damage is impaired whereas synthesis of RNA and protein is not. The cell regenerative ability of the testis with moderate tubular damage may be poor in spite of the preservation of testicular cell RNA and protein synthesis.