Androgen receptor isoforms in human prostatic cancer tissue and LNCaP cell line

Aim: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaP cell line. Methods: With high resolution isoelectric focusing (IEF) method we demonstrated the different expressions of AR isoforms in human prostatic cancer tissues and LNCaP cell line. Results: Data were obtained from three prostatic cancer specimens and the LNCaP cell line. Three types of AR isoforms were detected with pI values at 6.5,6.0, and 5.3. For the 3 prostatic cancer specimens, 1 sample showed all the three types of AR isoforms, the second specimen expressed at 6.5 and 6.0, and the third failed to show any type of isoforms. The LNCaP cell line expressed all the three AR isoforms. Binding of 3H-dihydrotestosterone (3H-DHT) to these three isoforms was inhibited by the addition ofl00-fold excess of DHT or testosterone, while not by progesterone, oestradiol and diethylstilboestrol. Conclusion: The expression of AR isofonns is different in different prostate cancer tissues, which may be related to the difference in the effect of anti-androgen therapy in different patients.

Fertility and sexual life of men after their forties and in older age

Owing to the demographic development, the aging male will require more consideration in future. In contrast to a rapid decline of estradiol during menopause in women, the process of aging in the male is retarded and subject to high individual variations. Impairment of spermatogenesis is observed as a continuous process occurring over decades. However, only about 50% of men in their eighties show complete loss of fertility. In principle, spermatogenesis may be retained well into senescence. Of importance for the individual health condition is the fact that the number of Leydig cells declines with advancing age. Thus, altered sex hormone concentrations in aging men result from both functional disturbances and a gradual reduction in Leydig cells. Furthermore, an impaired feed-back mechanism of the pituitary-gonadal axis occurs, with disappearance of the circadian testosterone (T) rhythm. LH and FSH levels are increased, and a reduced bioavailability of sex hormones is observed. Lower total testosterone concentrations in men over 60 years are accompanied by clinical signs of reduced virility, such as decreased muscle mass and strength as well as reduced sexual hair growth and libido. An age-related decline in androgen secretion and plasma testosterone levels therefore suggests the use of androgen supplementation. However, there is a lack of risk-benefit long-term studies. Increased research in the male is mandatory to meet the requirements of the aging population. This should include the availability of precise epidemiological data about the frequency of partial androgen deficiency in aging males (PADAM).

Role of androgen receptor in prostate cancer

The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80 % of prostate cancers initially respond to hormonal therapy, howcrver, more than half of the re-sponders gradtmlly become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnonnalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. "Ilais article focusedon the role of AR in the progression of prostate cancer.

Immunohistochemical observation on luteinizing hormone in rat testes before and after testicular capsulotomy

Aim: In the testicular capsulotomized rats, although there was a significant increase in the luteinizing hormone (LH) levels, the secretion of testosterone remained low. In order to clarify the mechanisms of this phenomenon, the binding of endogenous LH to the testes were observed before and after testicular capsulotomy. Methods: Peroxidase-antiperoxidase (PAP) method was used to detect the binding of LH to the testes in rats. Results: An intense positive s taining of LH was found in the Leydig cells of both the normal and sham-operated control testes. However, at 40 d after operation, the LH immunoreactivity was decreased in the Leydig cells of the capsulotomized testis. By d 60, only very weak positive staining could be observed in these cells. Conclusion: A progressive reduction of endogenous LH binding to the testis cccurred in the capsulotomized rat.

A novel E153X point mutation in the androgen receptor gene in a patient with complete androgen insensitivity syndrome

Aim: To study a 46, XY newbom patient with a phenotype suggestive of an androgen insensitivity syndrome to confirm an anomaly in the AR gene. Methods: Genomic DNA from leukecytes was isolated in order to analyze SRY gene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursorsfrom the testis was performed in order to study testosterone production and response to hCG stimulation in culture,Results: Surgical exploration disclosed two testes, no Wolffian structures and important Mullerian derivatives. The SRY gene was present in peripheral blood leukecytes. Sequencing of the AR gene evidenced a previously unreported G to T transversion in exon 1 that changed the normal gintamine 153 codon to a stop codon. Interstitial cell cultures produced sizable amounts of testosterone and were responsive to hCG stimulation. Conclusion: This E153X nonsense point mutation has not been described previously in cases of A/S, and could lead to the synthesis of a short truncated(153 vs 919 residues) non functional AR probably responsible for the phenotype of complete androgen insensitivity syndrome (CAIS). (Asian J Androl 1999 Jun; 1 : 73 - 77)

常服安定药会影响性功能

刊登于《美国临床精神病学》杂志的一篇文章指出,为了治疗精神分裂症而经常服用安定药的病人,其生殖腺分泌的荷尔蒙激素会减少甚至没有,进而导致生殖功能不良和性功能降低等一系列的性功能并发症。

Effect of ligustrum fruit extract on reproduction in experimental diabetic rats

To study the effect of ligustrum fruit on spermatogenesis and blood gonadal hormones in diabetic rats.Methods: Experimental diabetes was induced in male Wistar rats with streptozotocin. Ligustrum fruit extract was given by gastric gavage at a dose of crude drug 30 g@ kg- 1@ d- 1 for 110 days. The serum gonadadotropic hormones and testosterone were determined on d 60 and testicular histology examined on d 110. Results: In the control diabetic rats, the seminiferous tubules were dilated and the spermatogenic cells irregularly arranged. Spermatogenesis was arrested with the number of spermatids highly reduced and spermatozoa not observed. In the treated rats, all types of spermatogenic cells were practically normal. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH)and testosterone levels were higher in the treated than in the control rats, but the difference was insignificant. Conclusion: In experimental diabetic rats, ligustrum fruit extract protects the damaging effect of experimental diabetes on spermatogenesis.

Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells

AIM: TO explore the ability of recombinant toxin luteinizinghormone releasing hormone-Pseudomonas aeruginosaexotoxin 40 (LHRH-PE40) and LHRH binding to LHRH receptor(LHRHR) on the membrane surface of human liver cancerHEPG cells.METHODS: LHRH was labeled by using 12sI with enzymaticreaction. The affinity and receptor volume of LHP, H-PE40and LHRH binding to LHRHR on the membrane surface ofhuman liver cancer cells were measured with radioligandreceptor assay.RESULTS: The specific activity of LHRH labeled with 12sIwas 2.7x 104 kBq/l^L, and its radiochemical purity reachedto 99.2-99.7%. The binding of 12sI to LHRH was maximalfor 240 min in the warm cultivation, and this binding wasstabilized. The inhibiting rates of ~2SI-LHRH and LHRH onthe proliferation of human liver cancer HEPG cells werenot significantly different. On the basis of the saturationcurve of ~2SI-LHRH binding to the membrane LHRHR of HEPGcells, ~2SI-LHRH of lx10s cpm was selected for radioligandreceptor assay. The affinity constants (Kd) of LHRH-PE40and LHRH binding to the membrane LHRHR of HEPG cellswere 0.43~0.12 nmol/L and 4.86~ 1.47 nmol/L, respectively,and their receptor volumes were 0.37~0.15 l^mol/g and0.42=I=0.13 l^mol/g, respectively. The binding of LHRH-PE40to the membrane protein of normal liver cells was notobserved.CONCLUSION: The recombinant toxin LHRH-PE40 binding tothe membrane surface of LHRHR of human liver cancer HEPGcells was very strong, while the specific binding of it to normalliver cells was not observed. The results provide an importantexperimental basis for the clinical application of LHRH-PE.