Triiodothyronine regulates insulin-like growth factor-I binding to cultured rat pituitary cells.

Abstract Triiodothyronine (T(3)) stimulates the synthesis of growth hormone and enhances the growth of neoplastic rat pituitary somatomam-motrophs (GH cells) in culture. Moreover, T(3) has been shown to stimulate the production and secretion of an autocrine growth factor by these cells. We have previously demonstrated the presence of specific receptors for insulin-like growth factors (IGF) on GH cells. Since GH(3) cells contain mRNA encoding IGF-I, it has been suggested that IGF-I might act in an autocrine fashion in these cells. Therefore, it was of interest to learn how T(3) affects IGF-I binding to GH(3) cells. T(3) increased [(125)I]IGF-I binding in a time - and dose-dependent manner. After 48 h of exposure to T(3), an increase in IGF-I binding was seen with 10(-11)M T(3), maximizing with 10(-8)M T(3). When cells were exposed to 10(-8) T(3), [(125)I]IGF-I binding reached a maximum of 218 +/- 20.8% of control (+/-SEM, P < 0.002) after 72 h of incubation. Scatchard analysis indicated that T(3) did not alter the K(d) of IGF-I for its receptor, but that the total receptor number was increased. Dexamethasone (10(-7)M) inhibited the T(3)-induced increase in IGF-I binding, but glucocorticoid alone did not substantially alter receptor number. No significant change in insulin or IGF-II binding was seen after hormone treatment. 10(-8) M T(3) or IGF-I increased the growth of the GH(3) cells by >/=30%. Our data indicate that T(3) upregulates IGF-I binding in GH(3) cells without altering insulin binding and thereby provides a means for enhancing potential autocrine regulation in this cell line.

Testicular torsion with contralateral vanishing testis.

An infant with a left hydrocele and nonpalpable right testis had an antenatal ultrasonogram showing a left hydrocele and normal right testis. When left inguinal hydrocelectomy was performed, extravaginal torsion of the spermatic cord and a normal testis was discovered. The right spermatic cord ended in a testicular remnant. We propose that this was a case of bilateral antenatal torsion that would have resulted in bilateral vanishing testis syndrome had the left hydrocele not prevented vascular compromise when antenatal testicular torsion occurred. This case gives visible support to the theory that testicular remnants are the result of antenatal torsion.

Incontinence and vesical neck strictures following radical retropubic prostatectomy.

OBJECTIVES: To evaluate the incidence and severity of vesical neck strictures and urinary incontinence after radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: Between August 1983 and December 1991, 481 consecutive patients underwent RRP by 1 of 2 senior surgeons. Strictures were treated by passing a urethral sound. Incontinence was measured by asking patients for a daily "pad count" of pads required to control urinary leakage. Results were compared to patient age, tumor volume, number of neurovascular bundles spared, preoperative urinary complaints, and previous transurethral resection of the prostate. RESULTS: Of 456 patients with adequate follow-up to determine stricture formation, 82.5% had no strictures, 6.8% required a single dilation, 3.7% required 2 dilations, 3.1% required 3 dilations, and 3.9% required more than 3 dilations. Risk of stricture formation was unrelated to every variable studied. Of 458 patients with adequate follow-up to determine recovery of continence, 80.1% required no pads, 8.1% required 1 to 2 pads a day, 6.6% required 3 to 5 pads a day, and 5.2% were totally incontinent 1 year or more after surgery. Incontinence was closely associated with postoperative urinary urgency. CONCLUSIONS: Strictures are a common but easily managed complication of RRP for prostate cancer. Despite substantial surgical experience, we report a somewhat higher rate of postoperative incontinence than other recently reported series. Our experience is more closely matched by published surveys of patient-reported complications after RRP.

Pathological characteristics and prognosis of nonpalpable and palpable prostate cancers with a Hybritech prostate specific antigen of 4 to 10 ng./ml.

PURPOSE: We compared the surgical pathological findings and postoperative course of patients with palpable and nonpalpable prostate cancers. MATERIALS AND METHODS: All patients with untreated prostate specific antigen (PSA) 4 to 10 ng./ml. who underwent radical prostatectomy between December 1984 and December 1993 were reviewed to select 61 with clinical stage T1c (nonpalpable) with stages T2a to c (palpable) disease. RESULTS: Nonpalpable cancers were smaller (2.99 versus 4.42 cc for palpable tumors), had smaller volumes of Gleason grade 4 to 5 cancer (0.66 versus 1.32 cc, respectively) and were less likely to have positive surgical margins (13 versus 22%, respectively) or significant (1 cm. or more) capsular penetration (10 versus 26%, respectively). Nonpalpable and palpable cancers had similar rates of seminal vesicle invasion (3.3 versus 4.3%, respectively) and positive lymph nodes (1.6 versus 0%, respectively). More than 90% of patients with nonpalpable cancer were biochemically cancer-free postoperatively, and the remainder were alive with disease after a mean followup of 25.1 months, compared to 69% disease-fee, 28% alive with disease and 2.5% dead of prostate cancer after mean followup of 43.8 months among those with palpable disease. CONCLUSIONS: We conclude that nonpalpable prostate cancers are pathologically more favorable than palpable prostate cancers with PSA 4 to 10 ng./ml. Our preliminary results also indicate that nonpalpable cancers are less likely to recur postoperatively than palpable cancers with a similar PSA range.

Insulin-like growth factor-I is internalized after binding to the type I insulin-like growth factor receptor.

Receptor-mediated endocytosis may represent an important mechanism whereby peptide hormones exert their biological effects. The ability of recombinant insulin-like growth factor (IGF)-I to be internalized by cultured cells was evaluated in BRL-3A2 cells, a rat liver-derived cell line which lacks insulin receptors. Since recombinant IGF-I does not bind to the Type II IGF receptor, all specific binding of 125I-IGF-I in BRL-3A2 cells represents binding to the Type I receptor. Exposure of BRL-3A2 cells to IGF-I resulted in a rapid 50% downregulation of Type I IGF receptors. Only one-half of these binding sites were sensitive to treatment with trypsin, a phenomenon which indicates that the peptide and its receptor were internalized after the cells were exposed to IGF-I. In conclusion, these experiments demonstrate that IGF-I can be internalized by cultured cells via the Type I IGF receptor, and suggest that IGF hormone action may be exerted by receptor-mediated endocytosis.

Aberrant regulation of the metabolism of the insulin receptor in Swarm rat chondrosarcoma chondrocytes.

Treatment of Swarm rat chondrosarcoma chondrocytes for 3 days in media containing either non-recombinant pig or recombinant human insulin (1 micrograms/ml) increased the rate of proteoglycan synthesis approximately 6-fold compared with cells cultured in the absence of insulin. The concentrations of human and pig insulin that stimulated the cells to double their rate of proteoglycan synthesis were approximately 1 ng/ml and approximately 2 ng/ml respectively. Because physiological concentrations of insulin do not influence proteoglycan synthesis in non-transformed chondrocytes, the findings indicated a possible abnormality in the insulin-dependent regulation of the insulin receptor in these tumour cells. Like most cells, chondrosarcoma chondrocytes down-regulated their insulin receptors when incubated with insulin for 30 min. However, the number of plasma-membrane and intracellular insulin receptors did not decrease when the chondrocytes were exposed to insulin chronically for 4 days. Chondrocytes were cultured in media containing 2H-, 13C- and 15N-labelled amino acids, and the heavy-isotope density-shift method was used to investigate both the rate of degradation and the rate of synthesis of the insulin receptor. Although the rate of synthesis of the receptor was slightly faster in the insulin-treated cultures, as assessed by a slightly faster rate of appearance of the 'heavy' receptor, the rate of degradation of the receptor was slower in the insulin-treated cultures. The half-lives for the 'light' receptors were approx. 18 h and 10 h for chondrocytes cultured in insulin-containing and insulin-free media respectively. These studies in vitro indicate that the apparent up-regulation of insulin receptors that occurs in this transformed cell upon long-term exposure to insulin is primarily the result of a decreased rate of receptor degradation.

Biology and treatment of pediatric genitourinary tumors.

Treatment of childhood genitourinary tumors continues to advance through the use of collaborative protocols and a multidisciplinary approach. This paper reviews the 1993 literature, with an emphasis on Wilms' tumor, rhabdomyosarcoma, and testicular intraepithelial neoplasia and its relationship to testicular maldescent.

Nerve sparing radical prostatectomy: a different view.

Erectile dysfunction was evaluated in 459 men with prostate cancer before and after radical prostatectomy. Potency was defined as the ability to achieve unassisted intercourse with vaginal penetration. Of the patients 51 were potent postoperatively, including 2 of 187 (1.1%) undergoing surgery without nerve sparing, and 27 of 203 (13.3%) undergoing unilateral and 22 of 69 (31.9%) undergoing bilateral nerve sparing prostatectomy. Less than half of the patients who were sexually active postoperatively were satisfied with the erections or achieved intercourse at least once a month. Postoperative potency was statistically related to the number of neurovascular bundles spared, frequency of intercourse preoperatively, absence of seminal vesicle or lymph node involvement with cancer, absence of postoperative incontinence or strictures, patient age and cancer volume.