Correlation between Fluorescence in Situ Hybridization and Testicular Biopsy for the Prediction of Spermatogenesis in 37 Patients with Nonobstructive Azoospermia
Objectives: We applied interphase fluorescence in situ hybridization (FISH) to testis sections to examine the evidence of spermatogenesis in Patients with nonobstructive azoospermia. This technique was evaluated and compared with conventional testicular histopathologic findings for the possibility of additional clinical applications.
Materials and Methods: Thirty-seven consecutive patients with nonobstructive azoospermia were carefully evaluated clinically. Testes were biopsied for both sperm extraction and histopathologic examination. FISH staining was performed with a CEP 18 SpectrumAqua/CEP X SpectrumGreen/CEP Y SpectrumOrange probe.
Results: Eight of 11 cases (sensitivity 73%) that were found to have spermatids on the histopathologic slides also were proven to produce haploid cells by FISH staining. On the other hand, 21 of the 26 cases (specificity 81%) for which no spermatids could be found on the histopathologic slides also had only diploid cells by FISH staining. On the basis of the good correlation between the FISH staining and conventional histopathologic findings, we could confirm the diagnosis of spermatogenesis using both methods.
Conclusions: FISH staining of testicular sections allows more reliable prediction of spermatogenesis and provides benefits for a patient’s decision regarding fertility counseling
男性學論文獎臨床組2
Role of Testicular Interstitial Macrophages in Regulating Testosterone Release in Hyperprolactinemia
William J. Huang, 1,3 Jiun-Yih Yeh, 2 Shu-Fen Kan, 2 Luke S. Chang,1,3 and Paulus S. Wang 2*
1Department of Urology and Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, 11221, Republic of China
2Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, 11221, Republic of China
3Division of Urology, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan, Republic of China
Hyperprolactinemia-induced hypogonadism has been linked to a dysfunction of the hypothalamus-pituitary-testis axis. The direct inhibitory effects of prolactin on the testicular release of testosterone have also been demonstrated, though their mechanisms remain unclear. Incubation of rat testicular interstitial cells (TICs) with prolactin stimulated the release of testosterone. TICs from rats with anterior pituitary-grafting-induced hyperprolactinemia release lower amounts of testosterone than controls. However, Leydig cells isolated from anterior pituitary-grafted rats release a greater amount of testosterone. These paradoxical observations have remained unexplained. This study examined the roles of testicular interstitial macrophages and of their product, tumor necrosis factor-α(TNF-α), in regulating Leydig cells under condition of hyperprolactinemia. Hyperprolactinemia was induced by grafting two anterior pituitary glands of rats under the renal capsule. Control animals were grafted with rat cortex tissue. The rats were sacrificed 6 weeks later. TICs and macrophages, and Leydig cells were isolated for in vitro incubation and drugs challenge. Testosterone released by testicular interstitial or Leydig cells was measured by radiommunoassay. TNF-α concentration in the medium of TICs or macrophages was measured by enzyme-linked immunosorbent assay (ELISA). A dose-dependent stimulation of TNF-α secretion in the medium of TICs or macrophages by the prolactin challenge was observed. Higher amounts of TNF-α were released by TICs in the anterior pituitary-grafted rats than in the control group. In contrast, the released of TNF-αby testicular interstitial macrophages isolated from the anterior pituitary- and cortex-grafted groups was quantitatively similar. Challenge with human chorionic gonadotropin did not modify the TNF-α release by testicular interstitial macrophages in either group. Challenge of Leydig cells with TNF-αinhibited their release of testosterone stimulated by human chorionic gonadotropin, but not their basal testosterone release. These different patterns of testosterone release in TICs versus Leydig cells cultures in anterior pituitary-grafted rats may be due to the influence of testicular interstitial macrophages. These observations correlate with in vivo conditions, where prolactin increases the release of TNF-α by testicular interstitial macrophages, which, in turn, decreases the human chorionic gonadotropin-stimulated release of testosterone by Leydig cells. In summary, hyperprolactinemia-induced hypogonadism involves a mechanism of prolactin-originated, macrophage-mediated inhibitory regulation of testosterone release by Leydig cells. TNF-α, one of the cytokines secreted by macrophages, may play a key role in this mechanism.
男性學論文獎基礎組
Elevated Serum Chromogranin a Precedes Prostate-Specific Antigen Elevation and Predicts Failure of Androgen Deprivation Therapy in Patients with Advanced Prostate Cancer
Background and Purpose: Development of hormone-refractory prostate cancer (HRPC) may be due to outgrowth of neuroendocrine cells in the prostate gland. Increase in prostate-specific antigen (PSA) levels usually precedes clinical progression in patients failing hormone therapy. The timing of changes of PSA and chromogranin A (CgA) remains unclear. We analyzed serial serum levels of CgA and PSA in prostate cancer patients receiving androgen deprivation therapy (ADT).
Methods: From October 1998 through January 2003, 90 patients with locally advanced (n=20) or metastatic (n=70) prostate cancer receiving ADT were enrolled. Serial serum samples for PSA and CgA assay were collected before and every 3 months during ADT. The median follow-up was 35 months (range, 20 to 52 months).
Results: At least 3 serum samples were obtained during ADT in 78 patients. Among these patients, 36 (46.2%) had no PSA re-elevation (<4 ng/mL) and their CgA remained low (<84.6 ng/mL) throughout the treatment period. Another 17 patients (21.8%) also had low PSA (<4 ng/mL) but had progressively increasing CgA. The remaining 25 patients (32%) developed HRPC. Among them, 17 showed progressively elevation in CgA (>100 ng/mL), which was followed by PSA elevation after a median interval of 10 months. Interestingly, CgA levels decreased again upon reaching plateaus as PSA began to rise.
Conclusions: For patients with advanced prostate cancer receiving ADT, serum CgA, may be a useful tumor marker that precedes PSA elevation. Elevation of CgA during ADT signals ultimate treatment failure and may have clinical implications for implementation of novel therapies.