Lack of a direct effect of gonadotropin hormone-releasing hormone agonist on human testicular steroidogenesis.

In an attempt to determine whether the chronic administration of GnRH agonist (GnRH-A) has a direct inhibitory effect on testicular steroidogenesis in the human, the testes of four men with disseminated prostatic cancer who were treated with GnRH-A daily for at least 1 yr were assayed for intratesticular pregnenolone (5-pregnen-3 beta-ol-20-one), progesterone, dehydroepiandrosterone, 17 alpha-hydroxypregnenolone (5-pregnen-3 beta 17 alpha-diol-20-one), 17 alpha-hydroxyprogesterone, androstenedione, and testosterone (T). In addition, testicular 17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase enzyme activities of the delta 4 pathway were measured. These intratesticular steroids and enzyme activities from four GnRH-A-treated patients were compared to those in five men (controls) who were orchiectomized as the primary treatment for their disseminated prostatic cancer and in three other men who were treated for 3-12 months with GnRH-A daily but received, in addition to the daily GnRH-A, 1000 IUhCG, im, every other day for 3 days immediately before their salvage orchiectomy, which was performed when their disease progressed.

Hormonal regulation of testicular descent.

The involvement of testosterone in testicular descent and the mechanism of testicular descent were analyzed and discussed.

Mechanism of inhibition of human testicular steroidogenesis by oral ketoconazole.

To determine the antisteroidogenic effect of ketoconazole (KTZ) in the human testis, we measured the plasma delta 5-pregnenolone, delta 5-17 alpha-hydroxypregnenolone, dehydroepiandrosterone (DHEA), progesterone, 17 alpha-hydroxyprogesterone, androstenedione (A), and testosterone (T) concentrations in three men with previously untreated metastatic prostate cancer at various time intervals for 24 h before and 48 h after the administration of 200 mg oral KTZ every 8 h. The adrenal glands of these three patients were suppressed (as measured by the plasma cortisol levels) by the administration of 1.0 mg dexamethasone daily for 7 days before and during the study.

Cytomegaloviral epididymitis in a patient with the acquired immune deficiency syndrome.

We report on a patient with cytomegaloviral epididymitis and the acquired immune deficiency syndrome. The diagnosis was suggested by epididymitis that was refractory to antibiotics, and by isolation of cytomegalovirus from the urine and semen. The definitive diagnosis was made with immunohistochemical staining for cytomegaloviral antigens in the epididymal ductal cells.

Association between abdominal wall defects and cryptorchidism.

To determine whether intra-abdominal pressure may have a role in the process of testicular descent in man, we reviewed retrospectively the records of all male infants who presented during a 10-year period with severe abdominal wall defects, such as gastroschisis (28), omphalocele (29) and umbilical hernia (53), and calculated the incidence of cryptorchidism in these patients. The incidence of cryptorchidism at birth and at 1 year after birth was 18 and 15 per cent, respectively, in patients with gastroschisis, 52 and 33 per cent, respectively, in those with omphalocele, and 6 and 6 per cent, respectively, in those with umbilical hernia. For all 3 disorders the incidence of cryptorchidism was higher than in documented historical controls.

Pyelovesicostomy as a form of urinary reconstruction in renal transplantation.

The development of ureteral obstruction or ureteral fistula formation in the renal transplant recipient usually requires surgical repair. This involves reconnecting the donor ureter to either the recipient ureter (ureteroureterostomy) or bladder (ureteroneocystostomy), or creating an anastomosis between the renal pelvis and recipient native ureter (pyeloureterostomy). Occasionally, the donor or recipient ureter is absent, necrotic or diseased so that a ureteroureterostomy, ureteroneocystostomy or pyeloureteral anastomosis cannot be performed.

Comparison of the efficacy of subcutaneous and nasal spray buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer.

The comparative efficacy of subcutaneous injections and intranasal spray in the maintenance of suppression of testicular function in men with advanced prostatic cancer treated with a gonadotropin-releasing hormone (GnRH) agonist, Buserelin, was evaluated in a nonrandomized clinical trial. After a common induction period of 1 week's treatment with 500 micrograms three times daily by subcutaneous injection, patients were allocated into one of two groups for maintenance therapy with either subcutaneous (200 micrograms once daily) or intranasal (400 micrograms nasal spray three times daily) Buserelin therapy. Plasma luteinizing hormone (LH) and sex steroid (testosterone [T], dihydrotestosterone [DHT], and estradiol [E2]) patterns were studied before the start and at days 1, 7, and 14 and months 2, 4, 6, and 12 on maintenance regimens.

Luteinizing hormone and follicle-stimulating hormone responses to intransal gonadotropin-releasing hormone.

For determination of the dose-response relationships of plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to the intranasal administration of gonadotropin-releasing hormone (GnRH), normal adult men were administered doses of 100, 200, 400, and 800 micrograms of GnRH on separate days, and plasma LH and FSH were measured before and after nasal insufflation of GnRH. Plasma LH was increased after a minimum dose of 200 micrograms GnRH. Median peak plasma LH levels occurred 30 minutes after intranasal GnRH and followed a log-dose relationship.

Hormonal effects of ketoconazole in vivo in the male rat: mechanism of action.

Ketoconazole, an antifungal agent, has been shown to lower serum testosterone (T) in man. Measurements of circulating precursors of T suggest that ketoconazole may inhibit 17,20-desmolase activity in the testis. To further elucidate its mechanism of action in vivo, we studied its effects on the pituitary-gonadal axis in the male rate.

Hormonal therapy of cryptorchidism. A randomized, double-blind study comparing human chorionic gonadotropin and gonadotropin-releasing hormone.

We conducted a randomized, double-blind study comparing intranasal gonadotropin-releasing hormone (1.2 mg per day for 28 days) with parenteral human chorionic gonadotropin (3300 IU per week for four weeks) in the treatment of cryptorchidism in 33 boys one to five years old (29 with unilateral and 4 with bilateral cryptorchidism). Testicular descent into the scrotum occurred in 3 of the 16 patients (19 percent) treated with gonadotropin-releasing hormone and in 1 of the 17 (6 percent) treated with human chorionic gonadotropin (P = 0.

Recurrent respiratory disease, azoospermia, and nasal polyposis. A syndrome that mimics cystic fibrosis and immotile cilia syndrome.

Three adult men with chronic sinopulmonary disease, nasal polyposis, and azoospermia were studied. All had normal sweat chloride values and pancreatic function. The azoospermia was due to a block in the epididymis that was distinguishable from the defect in the vas deferens seen in cystic fibrosis.

UCLA conference. Infertility in the male.

Male infertility is a common and distressing problem in which reproductive abnormalities frequently play an important role. Assessment requires an understanding of the control of spermatogenesis and factors responsible for normal sperm function. Standard tests for assessment of semen quality frequently fail to detect impaired function, but newer tests are now available to measure sperm movement and their ability to penetrate the ovum.

Effect of in vitro ketoconazole on steroid production in rat testis.

In an attempt to confirm where in the testosterone (T) biosynthetic pathway of the rat testis ketoconazole (KTZ) inhibits T production, rat testicular mince was incubated with either 10 micrograms/ml or 100 micrograms/ml KTZ in the presence and absence of hCG (1 IU), and intratesticular pregnenolone (delta 5P), progesterone (P), 17-alpha-hydroxyprogesterone (17 alpha-HP), androstenedione (A) and testosterone (T) were assayed. In the absence of hCG, 10 micrograms/ml KTZ was sufficient to reduce intratesticular T by 80%. At this concentration of KTZ, intratesticular 17 alpha-HP (ng/g testis, mean +/- SEM) increased from 0.

Assay system for simultaneous measurement of three steroidogenic enzyme activities in rat and human testis--effect of human chorionic gonadotropin.

An assay system that measures the enzymatic activities (17 alpha-hydroxylase, 17,20-desmolase, and 17 beta-hydroxysteroid dehydrogenase) in the delta 4 pathway of testosterone biosynthesis using rat and human testicular homogenate was examined. This system involves the simultaneous separation of the steroid intermediates by a three-step TLC procedure. The observed Rf values were 0.

Impaired testosterone biosynthesis in cryptorchidism.

In an attempt to determine whether the production and synthesis of testosterone (T) by the testis is impaired by the cryptorchid state, the ability of the cryptorchid rat testis to form T was assessed at various time periods into adulthood after the surgical induction of cryptorchidism in the newborn period. The intratesticular T content of the descended testis rose from 0.3 ng/testis at 14 days of age to 71.

In vitro inhibition of testosterone biosynthesis by ketoconazole.

Oral ketoconazole has been demonstrated to lower plasma testosterone in man. Measurement of blood precursors of testosterone suggest that ketoconazole may have its effect inhibiting the 17,20-desmolase enzyme within the testis. To substantiate this, a series of in vitro experiments was conducted using the rat testis to determine where in the testosterone biosynthetic pathway ketoconazole has its effect.

Testicular histology following chronic gonadotropin-releasing hormone agonist treatment.

The histologic appearance of the testes of men exposed to chronic gonadotropin-releasing hormone agonist (GnRH-A) therapy has not been previously documented. Herein, we report on the histologic features of the testes of four patients with disseminated prostatic carcinoma who received at least 1 year of daily treatment with (D-Leu6, des-Gly-NH2(10), proethylamide9)-GnRH (leuprolide, Abbott Laboratories, North Chicago, IL) for their disease, and subsequently underwent bilateral orchiectomy. In marked contrast to the testes from five control patients, the testes of these agonist-treated patients demonstrated absence of spermatogenesis, Leydig cell hypoplasia, and Leydig cell inactivity.

Silicate urolithiasis.

Urinary tract silicate calculi are rare. Occurrence is limited strictly to patients who ingest magnesium trisilicate antacids. We report a case of a renal silicate calculus and review the subject of silicate stones.

Interstitial Tamm-Horsfall protein in rejecting renal allografts. Identification and morphologic pattern of injury.

In a study of renal allografts with acute rejection primarily or exclusively of the cellular type, extratubular Tamm-Horsfall protein was identified in 63.6% of the specimens, representing 76.1% of the patients whose tissues were examined.

Effects of chronic D-Leu6, des-Gly10-gonadotropin releasing hormone ethylamide on male sex tissues.

The chronic administration of superactive agonists of gonadotropin releasing hormone (GnRH-A) have been reported to have a direct inhibitory effect on the sex tissues of the male rat. In an attempt to confirm or refute this statement, adult male rats were either left intact or were castrated and then treated daily for 14 days with either testosterone (T), dihydrotestosterone (DHT) or sesame oil (vehicle). Half of the intact and castrate animals also received daily injections of 200 ng of the GnRH agonist, D-Leu6, des-Gly10-GnRH ethylamide for 14 days.

Role of the gubernaculum and intraabdominal pressure in the process of testicular descent.

In an attempt to more accurately define the role of the gubernaculum in the descent of the testis, a series of microsurgical procedures was performed in the newborn rat and the incidence of testicular descent was noted 4 weeks later. When the proximal attachment of the gubernaculum to the testis/epididymis was severed, descent occurred in 17 of 17 (100 per cent) of the testes. When the distal attachment of the gubernaculum to the scrotum was severed, 0 of 10 (0 per cent) of the testes descended.

Synergy of abdominal pressure and androgens in testicular descent.

The potential synergistic activity between intra-abdominal pressure and androgens in facilitating testicular descent was investigated in the rat. In the rat, the testis normally descends on or about the 21st day of age. If one testis is excised at 14 days of age and replaced by a silicone prosthesis, the silicone prosthesis will descend into the scrotum in approximately 11/20 (55%) of the animals by 28 days of age.

Effect of GnRH superactive analogs (alone and combined with androgen) on testicular function in man and experimental animals.

GnRH long acting agonists, when given chronically, are potent inhibitors of testicular function in both man and experimental animals. Administration of these agents to male rats and to men results in suppression of testosterone secretion and diminished sperm counts. Despite the similarity of these observations the mechanisms by which these agents effect the testes appear to be different in the two species.