The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications

Petrow, V.

doi:10.1002/pros.2990090405

Cited by 58 publications

(28 citation statements)

References 69 publications

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“…An¬ other androgen, namely mesterolone, is likewise unable to suppress gonadotropins (Petry et al estrogens (Wilson 1980(Wilson , 1987 and the lack of estradiol elevation under testosterone TTS may prevent prostatic growth. The role of testosterone and DHT in the origin of prostatic cancer remains controversial (Petrow 1986). The observation by Meikle & Stanish (1983) of low rather than high serum DHT levels in men at risk for prostatic carcinoma may even suggest a protective effect of DHT.…”

Section: Discussionmentioning

confidence: 99%

Substitution therapy of hypogonadal men with transdermal testosterone over one year

Bals‐Pratsch

Langer

Place³

et al. 1988

Acta Endocrinologica

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Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3\p=n-\5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/ testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment.Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.

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Section: Discussionmentioning

confidence: 99%

Substitution therapy of hypogonadal men with transdermal testosterone over one year

Bals‐Pratsch

Langer

Place³

et al. 1988

Acta Endocrinologica

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“…Moreover, antiandrogens inhibit prostate growth in vitro (12) and in vivo (13). It is also known that, testosterone is irreversibly converted to dihydrotestosterone (DHT) within the prostate gland by the 5-␣a-reductase enzyme, and that DHT is the active androgen in the prostate (14). Human prostate growth is also regulated by growth factors such as epidermal growth factor (EGF), and it was recently shown that progression to prostate cancer is correlated with disruption of EGF signaling (15).…”

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confidence: 99%

Ca2+ Pools and Cell Growth

Legrand¹,

Humez²,

Slomianny³

et al. 2001

Journal of Biological Chemistry

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The present study demonstrates for the first time that intracellular calcium-ATPases and calcium pool content are closely associated with prostate cancer LNCaP cell growth. Cell growth was modulated by changing the amount of epidermal growth factor, serum, and androgene in culture media. Using the microspectrofluorimetric method with Fura-2 and Mag Fura-2 as probes, we show that in these cells, the growth rate is correlated with intracellular calcium pool content. Indeed, an increased growth rate is correlated with an increase in the calcium pool filling state, whereas growth-inhibited cells show a reduced calcium pool load. Using Western blotting and immunocytochemistry, we show that endoplasmic reticulum calcium pump expression is closely linked to LNCaP cell growth, and are a common target of physiological stimuli that control cell growth. Moreover, we clearly demonstrate that inhibition of these pumps, using thapsigargin, inhibits LNCaP cell growth and prevents growth factor from stimulating cell proliferation. Our results thus provide evidence for the essential role of functional endoplasmic reticulum calcium pumps and calcium pool in control of prostate cancer LNCaP cell growth, raising the prospect of new targets for the treatment of prostate cancer.

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“…Furthermore, it is postulated that testosterone that is converted peripherally to dihydrotestosterone (DHT) by 5-alpha reductase is responsible for this risk (Petrow, 1986) DHT has a role in the growth of prostatic tissue and therefore can infl uence lower urinary tract symptoms. Testosterone is aromatized to form estradiol (E2) in fatty tissue and leads to increased aromatase activity, resulting in increased levels of estradiol (Hudak et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Effect of furostanol glycosides from Trigonella foenum‐graecum on the reproductive system of male albino rats

Aswar

Bodhankar

Thakurdesai

2010

Phytotherapy Research

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Trigonella foenum (TF) has long been used in the traditional Indian systems of medicine for the treatment of various ailments. The objective was to study the anabolic and androgenic activity of the furostanol glycosides fraction of Trigonella foenum-graecum (Fenu-FG) in immature castrated male Wistar rats. It was also aimed to investigate the effect of Fenu-FG on testicular histology in non-castrated immature rats. The animals (55 ± 5 g) were castrated. The rats were treated with either vehicle, testosterone (10 mg/kg s.c. bi-weekly) or Fenu-FG (10 and 35 mg/kg p.o.) once daily for 4 weeks. At the end of the study, blood was withdrawn, serum testosterone and BUN were measured. Animals were killed and reproductive organs were excised and weighed.Fenu-FG (35 mg/kg p.o.) and testosterone (10 mg/kg, s.c. biweekly) increased the weight of the levator ani muscle as well as body weight. Fenu-FG (10 or 35 mg/kg p.o.) did not change the testosterone level in castrated rats. Histopathological examination of the testis of non-castrated rats treated with Fenu-FG (10, 35 mg/kg p.o.) showed normal architecture of the testis. Fenu-FG (35 mg/kg p.o.) showed anabolic activity without androgenic activity.

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The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications

Cited by 58 publications

References 69 publications

Substitution therapy of hypogonadal men with transdermal testosterone over one year

Substitution therapy of hypogonadal men with transdermal testosterone over one year

Ca2+ Pools and Cell Growth

Effect of furostanol glycosides from Trigonella foenum‐graecum on the reproductive system of male albino rats

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