Tetrahydroisoquinoline alkaloids mimic direct but not receptor-mediated inhibitory effects of estrogens and phytoestrogens on testicular endocrine function. Possible significance for Leydig cell insufficiency in alcohol addiction

Stammel, Waltraud; Thomas, Helmut; Staib, W.; Kühn‐Velten, W. Nikolaus

doi:10.1016/0024-3205(91)90196-i

Cited by 16 publications

(7 citation statements)

References 38 publications

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“…In this study, no clear association for prostate cancer was seen with amount of tobacco use (11). The pattern of increasing risk with increasing alcohol consumption is also apparent in each subgroup defined by increasing tobacco use (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), and 40 or more packyears). In addition, the association of alcohol use with prostate cancer was substantively unchanged by statistical adjustment for other potential confounders that included education, income, body mass index, nonalcohol caloric intake, fat intake, fruit and vegetable consumption, history of liver cirrhosis, and family history of prostate cancer.…”

Section: Resultsmentioning

confidence: 58%

Alcohol Use and Prostate Cancer Risk in US Blacks and Whites

Hayes

Brown

Schoenberg

et al. 1996

American Journal of Epidemiology

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Prostate cancer is the most common malignancy in US men (more than 165,000 cases per annum) and occurs substantially more frequently in blacks than in whites. The causes of this disease are, however, poorly understood. Alcohol consumption, which has been clearly related to malignancies of the upper aerodigestive tract, may also increase risk of cancer at other sites, including the prostate. The authors investigated alcohol use as a risk factor for prostate cancer among US blacks and whites. A population-based, case-control study was carried out among 981 men (479 blacks and 502 whites) with pathologically confirmed prostate cancer diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 blacks and 721 whites) who resided in Atlanta, Georgia; Detroit, Michigan; and 10 counties in New Jersey, geographic areas covered by three population-based cancer registries. In-person interviews elicited information on alcohol use and other factors possibly related to prostate cancer. Compared with never-users, risk for prostate cancer increased with amount of alcohol drunk (chi2 (trend), p < 0.001), with significantly elevated risks seen for those who had 22-56 drinks per week (odds ratio = 1.4; 95% confidence interval 1.0-1.8) and 57 or more drinks per week (odds ratio = 1.9; 95% confidence interval 1.3-2.7). The finding was consistent among blacks (chi2 (trend), p < 0.01) and whites (chi2 (trend), p < 0.05), and among young and old subjects; it was not restricted to a specific type of alcoholic beverage. In this first large study among US blacks and whites, increased risk for prostate cancer was associated with increased alcohol use. The risk was similar for whites and blacks and could not be attributed to tobacco use or to a number of other potential confounders.

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Section: Resultsmentioning

confidence: 58%

Alcohol Use and Prostate Cancer Risk in US Blacks and Whites

Hayes

Brown

Schoenberg

et al. 1996

American Journal of Epidemiology

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“…Interestingly, there was no effect on T production when immature Leydig cells were incubated with various concentrations of E and DES. Data from previous studies have been variable and/or showed that relatively high doses of E are required to suppress T production by rat Leydig cells in vitro [4,[48][49][50]. On the other hand, the direct and inhibitory effects of E and DES on Leydig cell function in vivo have been clearly demonstrated.…”

Section: Discussionmentioning

confidence: 91%

A Metabolite of Methoxychlor, 2,2-Bis(p-Hydroxyphenyl)-1,1,1-Trichloroethane, Reduces Testosterone Biosynthesis in Rat Leydig Cells Through Suppression of Steady-State Messenger Ribonucleic Acid Levels of the Cholesterol Side-Chain Cleavage Enzyme1

Akingbemi

Klinefelter

et al. 2000

Biology of Reproduction

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Postnatal development of Leydig cells involves transformation through three stages: progenitor, immature, and adult Leydig cells. The process of differentiation is accompanied by a progressive increase in the capacity of Leydig cells to produce testosterone (T). T promotes the male phenotype in the prepubertal period and maintains sexual function in adulthood; therefore, disruption of T biosynthesis in Leydig cells can adversely affect male fertility. The present study was designed to evaluate the ability of a xenoestrogen, methoxychlor (the methoxylated isomer of DDT [1,1, 1-trichloro-2,2-bis(p-chlorophenyl)ethane]), to alter Leydig cell steroidogenic function. Purified progenitor, immature, and adult Leydig cells were obtained from, respectively, 21-, 35-, and 90-day-old Sprague-Dawley rats treated with graded concentrations of the biologically active metabolite of methoxychlor, 2, 2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), and assessed for T production. HPTE caused a dose-dependent inhibition of basal and LH-stimulated T production by Leydig cells. Compared to the control value, reduced T production by progenitor and immature Leydig cells was apparent after 10 h of HPTE treatment in culture; the equivalent time for adult Leydig cells was 18 h. The reversibility of HPTE-induced inhibition was evaluated by incubating Leydig cells for 3, 6, 10, 14, or 18 h and measuring T production after allowing time for recovery. After treatment with HPTE for 3 h, T production by immature and adult Leydig cells for the 18-h posttreatment period was similar to the control value, but that of progenitor Leydig cells was significantly lower. The onset of HPTE action and the reversibility of its effect showed that Leydig cells are more sensitive to this compound during pubertal differentiation than in adulthood. T production was comparable when control and HPTE-treated immature Leydig cells were incubated with pregnenolone, progesterone, and androstenedione, but HPTE-treated Leydig cells produced significantly reduced amounts of T when incubations were conducted with 22R-hydroxycholesterol (P < 0.01). This finding suggested that HPTE-induced inhibition of T production is related to a decrease in the activity of cytochrome P450 cholesterol side-chain cleavage enzyme (P450(scc)) and cholesterol utilization. The reduced steady-state mRNA level for P450(scc) in HPTE-treated Leydig cells was demonstrated by reverse transcription-polymerase chain reaction and densitometry. In conclusion, this study showed that HPTE causes a direct inhibition of T biosynthesis by Leydig cells at all stages of development. This effect suggests that reduced T production could be a contributory factor in male infertility associated with methoxychlor and, possibly, other DDT-related compounds.

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“…SAL is sufficiently potent and selective in vivo to account for the massive discharge of PRL that occurs after physiological changes. At the same time, parallel with its DA depleting effect in sympathetically innervated peripheral organs, SAL can reduce testosterone secretion both in vivo and in vitro from Leydig cells [19][20]. Based upon all of these data, the aim of our present studies was to confirm the suppressive effects of hyperprolactemia induced by grafting pituitary glands under the kidney capsule and to investigate the effect of a single injection of SAL on the elevation of plasma PRL and on sexual behavior in male rats.…”

Section: Introductionmentioning

confidence: 79%