Evaluating polymorphic status of glutathione-S-transferase genes in blood and tissue samples of prostate cancer patients.

Prostate cancer is the most common urologic malignancy, involving multiple factors. There is evidence that suggests that detoxification enzymes and growth factors may play a role in its development . The glutathione S-transferase (GST) enzymes detoxify several carcinogens and genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been reported to be associated with prostate cancer, mainly from blood samples. As expression studies suggest differential expression of different genes in tissues, we hypothesize that polymorphic status may be differently expressed for GSTM1, GSTT1 and GSTP1 gene in blood and tissues of prostate cancer patients and BPH controls, impacting on the development of prostate cancer. To study this, we extracted DNA from blood and tissue samples of patients undergoing biopsy procedures or transurethral resection of prostate tissue. Genotyping for GSTM1 and T1 was conducted by multiplex PCR and for GSTP1 by the PCR-RFLP method. Our results suggested no significant differences in frequency distribution of M1, T1 and P1 between blood and tissue samples of patients and controls, but in a few patients differences in polymorphic status were observed. However, they were not significant. Furthermore, we observed a significant risk of prostate cancer with null allele of GSTT1 and GSTM1 and Val allele of GSTP1, supporting our previous findings. A study with large sample size using radical prostectomy tissue now needs to be performed to attain a specific conclusion.

Dorsolateral prostatic phosphomonoesterases and adenosine triphosphatases in hypo- and hyperthyroid rats.

Specific activities of phosphomonoesterases (acid and alkaline phosphatases) and adenosine triphosphatases (Mg2+, Ca2+ and Na+/K+ dependent ATPases) of dorsolateral prostate were studied in albino rats, under altered thyroid hormone status. Thyroidectomy induced hypothyroidism and thyroxine administered hyperthyroidism (25 micrograms/100 g body wt/day for 60 days, im) showed no impact on the activity of acid phosphatase. Three fold decrease in the activity of alkaline phosphatase was observed in hyperthyroid group. Ca2+ and Mg2+ dependent ATPases were significantly decreased in hypo- and hyperthyroid status whereas Na+/K+ ATPase was decreased in hyperthyroidism and showed an opposite trend in hypothyroid group.

Ventral prostatic phosphomonoesterases and adenosine triphosphatases in hypo- and hyperthyroid albino rats.

Specific activities of prostatic phosphomonoesterases (acid and alkaline phosphatases) and adenosine triphosphatases (Mg2+, Ca2+ and Na+/K+ dependent ATPases) were studied in albino rats, under altered thyroid hormone status. Thyroidectomy induced hypothyroidism decreased the specific activities of acid and alkaline phosphatases, Na+/K+ and Ca2+ dependent ATPases in ventral prostate. Hyperthyroidism (25 micrograms thyroxine/100g body weight/day for 60 days, im) enhanced the activities of acid phosphatase and Na+/K+ dependent ATPase, while Ca2+ dependent ATPase decreased. The altered thyroid status had no effect on the activity of ventral prostatic Mg2+ dependent ATPase. The data obtained in the present study showed differential and specific responses of various ventral prostatic phosphatases to the hypo or hyperthyroid status. The study also shows the necessity of an optimum level of thyroid hormones to maintain the normal activities of these enzymes and their secretory function in ventral prostate.

Influence of prolactin, androgens and bromocriptine on seminal vesicular and prostatic adenosine triphosphatases in castrated adult monkeys Macaca radiata.

E ects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on specific activities of adenosine triphosphatases (ATPases) of seminal vesicles and cranial and caudal prostates were studied in castrated adult bonnet monkeys. Castration decreased all ATPases (sodium/potassium, magnesium and calcium dependent) of seminal vesicles and both the lobes of prostate. PRL restored the normal activities of all ATPases in both the organs. Br given alone decreased all ATPases of prostate but caused no significant alteration, particularly calcium dependent ATPases of seminal vesicles and caudal prostate. TP/DHT replacement restored all ATPases of both the organs to the normal levels. PRL + TP/DHT further enhanced all the ATPases activities of all the regions studied. Br + TP/DHT decreased all ATPases but it did not produce any alteration in the calcium ATPases of seminal vesicles. The results suggest that prolactin facilitates membrane transport enzymes in the cranial and caudal prostate and seminal vesicles of adult castrated bonnet monkeys.

Catepsina D de próstata humana / Cathepsin D from human prostate

En este trabajo se ha desarrollado una metódica simple que ha permitido la obtención de catepsina D de próstata humana en cantidades apreciables para estudios enzimáticos y químicos, empleando cromatografías combinadas de intercambio en DEAE celulosa y cromatoenfoque en gel PBE-94. La síntesis química de un nuevo sustrato sintético permitió comparar la actividad hidrolítica de la catepsina D con las gastricsinas de próstata y líquido seminal humano, así como con pepsina y gastricsina de mucosa gástrica. La actividad de la catepsina prostática sobre el sustrato sintético N-acetil-L-fenilalanil-L-diyodotirosil-L-valina metil éster (APDTV) fué similar a la de las gastricsinas y mucho mayor con respecto a la pepsina. Las relaciones ácido glutámico/ácido aspártico (Glu/Asp) y leucina/isoleucina (Leu/Ile) de la catepsina D son semejantes a las presentes en las gastricsinas y no en las pepsinas, en cuyo caso estos aminoácidos se encuentran en una razón inversa

Clinical significance of serum lactate dehydrogenase, phosphohexose isomerase, aldolase and hexokinase in prostatic carcinoma.

The enzyme activities of Lactate dehydrogenase (LDH). prostate fluid LDH isoenzymes phosphohexose isomerase (PHI), Aldolase (ALD) and Hexokinase (HK) were determined in the sera of 77 samples of males. There were 12 cases of carcinoma prostate with metastases, 15 without metastases, 25 with benign prostatic hypertrophy and 25 nontumor. The enzyme activities of nontumor and benign group were statistically similar. The prostatic fluid LDH5/LDH1 ratio and PHI has been found to be the most sensitive parameter for detecting carcinoma prostate. Serial determinations of LDH, PHI, ALD and HK were found valuable for following the course of the disease during therapy.

Adenosine triphosphatase systems in genital tract of testosterone treated male adult monkeys.

Studies on the distribution of Na+, K+-dependent, Mg2+ dependent and Ca2+ dependent Adenosine Triphosphatase (ATP-ases) in the testes, epididymis, seminal vesicles and prostate glands of mature bonnet monkeys were carried out with and without Testosterone propionate (TP) treatment. Comparatively, the Ca2+ dependent ATP-ase was very active in the testes, caput and cauda epididymis and prostate of control animals. However, the Mg2+-dependent ATP-ase activity was predominant in the seminal vesicles. In all the genital tissues the Na+, K+ dependent ATP-ase exhibited low activity compared to other ATP-ase systems. On TP treatment at 1 mg/kg body wt. dose for 30 consecutive days to the second group of animals, all classes of ATP-ases drastically decreased in the testes, cauda epididymis, seminal vesicles and prostate. While in caput epididymis the Mg2+-dependent ATP-ase was stimulated, the Na+, K+-dependent ATP-ase was decreased both in the caput and corpus epididymis by the hormone treatment. The present study reveals the general inhibitory influence on the ATP-ase systems and thereby ionic transport after long term TP administration.