Acutely Administered Ethanol Participates in Testosterone Synthesis and Increases Testosterone in Rat Brain (original) (raw)
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Effects of alcohol on the hypothalamic-pituitary-gonadal axis in the male rat
PubMed, 1977
The effects of acute and chronic alcohol administration on serum testosterone and luteinizing hormone (LH) levels were examined in the male rat. Chronic alcohol administration resulted in depressed serum testosterone and LH levels when alcohol-fed rats were compared with rats maintained, ad libitum, on rat chow and water. However, neither testosterone nor LH levels were significantly lower in alcohol-treated rats when comparisons were made to pair-fed control animals, indicating that the nutritional deficits imposed by the chronic alcohol-feeding regimen contributed heavily to the observed reductions in the two hormones. To avoid the problems associated with a chronic drug delivery model, we injected rats with a single acute injection of alcohol. LH levels dropped significantly within 2 hours after the injection of a 2.5 g/kg dose of alcohol and remained depressed, at a level between 25 and 30% of control values, from 2 to 4 hours. By 6 hours after the injection, LH levels had returned to base-line levels. Testosterone levels were also reduced by alcohol, but this drop was not significant until at least 3 hours after the injection. Testosterone levels did not return to control levels throughout the 6-hour course of the experiment. Dose-response determinations revealed that alcohol produced a biphasic effect on serum testosterone and LH: low doses of alcohol significantly increased testosterone and LH, whereas high doses decreased the levels of both hormones. The results of these studies suggest that the ability of alcohol to depress serum testosterone levels, and thus produce symptoms of hypogonadism in the male of several species, is due to a primary effect of alcohol on the hypothalamic-pituitary aspect of the hypothalamic-pituitary-gonadal axis.
Testosterone Increases in Men After a Low Dose of Alcohol
Alcoholism: Clinical and Experimental Research, 2003
Heavy acute alcohol drinking decreases blood testosterone in men due to an effect on the testicular level. An acute increase in blood testosterone levels after a low alcohol dose has, however, recently been reported in women. The objective of this investigation was to study the effect of a low alcohol dose on testosterone in men and further elucidate the mechanism behind the effect by using 4-methylpyrazole, an inhibitor of alcohol metabolism. A double-blind placebo-controlled interventional crossover trial in random order (n = 13). After intake of alcohol (0.5 g/kg, 10% w/v), an acute increase in plasma testosterone (from 13.5 +/- 1.2 nmol/liter to 16.0 +/- 1.6 nmol/liter, mean +/- SEM; p < 0.05), a decrease in androstenedione (from 5.1 +/- 0.4 nmol/liter to 4.0 +/- 0.3 nmol/liter; p < 0.05), and an increase in the testosterone:androstenedione ratio (from 2.8 +/- 0.3 to 4.2 +/- 0.4; p < 0.01) were observed. The effects were not observed during pretreatment with 4-methylpyrazole (10-15 mg/kg orally), which inhibited the ethanol elimination rate by 37 +/- 3%. Alcohol intake affects the androgen balance in men through an effect mediated by the alcohol-induced change in the redox state in the liver.
The Journal of steroid biochemistry and molecular biology, 1990
The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedion...
Biochemical Pharmacology, 1983
It is rapidly becoming accepted, without direct evidence, that a change in the NAD-/NADH ratio in the testes produced by the metabolism of ethanol is the principal mechanism involved in its now well-established effects on testicular steroidogenesis. The purposes of the present studies were 2-fold: (1) to examine whether, in fact, in vivo or in vitro ethanol exposure alters the NAD-/NADH ratio in the testes; and (2) to examine the validity of previous reports in which it was found that NAD-prevented the effects of ethanol on testicular steoidogenesis under in vitro conditions. With regard to the first objective, we found that a large dose of ethanol (2.5 g/kg) markedly reduced gonadotropin-stimulated testicular steroidogenesis in vivo in the male rat, but it did not alter the NAD-and NADH concentrations in the testes. Similarly, extremely high ethanol concentrations (200mM) substantially suppressed hMG-stimulated testosterone biosynthesis in in vitro Leydig cell preparations, but no change in NAD + concentration occurred; NADH levels were very low in the Leydig cell preparations (less than 2% of NAD+ levels), but did not appear to change as a function of ethanol exposure. Finally, in contrast to previously published results, we found that NAD + (1 raM) did not prevent the in vitro effects of ethanol on cAMP-stimulated testicular steroidogenesis. Consequently, our results fail to support the hypothesis that acute in vivo or in vitro ethanol administration inhibits the biosynthesis of testosterone by altering the NAD÷/NADH ratio in the testes.
Endocrine, 2003
Although ethanol has been repeatedly demonstrated to inhibit the hypothalamo-pituitary-testes axis by multiple mechanisms, plasma testosterone levels can be normal in alcoholics who do not exhibit severely compromised liver function and even increased in some abstinent alcoholics, suggesting that adaptive changes to chronic alcohol abuse may alter these regulatory mechanisms. To address this variability, we have investigated the effects of chronic ethanol and withdrawal on rat testosterone regulation using a well-characterized liquid diet model that we have previously demonstrated to (1) provide daily oral ethanol consumption that produces behaviorally relevant plasma ethanol levels during the active (awake) stage of the photoperiod; (2) establish physical dependence on ethanol; and (3) produce not only hypothalamo-pituitary-adrenal axis, but also behavioral (anxiety-like behavior, response to novelty, sucrose preference) changes consistent with those of actively drinking and subseq...
Effects of chronic ethanol ingestion on steroid profiles in the rat testis
Biochimica et biophysica acta, 1986
Testosterone, seven of its potential precursors, three of its metabolites and estradiol were analyzed in testes from rats given ethanol for 23 days in a nutritionally adequate liquid diet. The results were compared to those obtained with pair-fed control rats. The concentrations of pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione and testosterone were markedly lowered in four of the five rats given ethanol. The concentrations of the other 3 beta-hydroxy-delta 5 steroids and estradiol were unchanged, resulting in significantly increased ratios between 17-hydroxypregnenolone and 17-hydroxyprogesterone (P less than 0.025) and between androstenediol and testosterone (P less than 0.025) in the ethanol-treated rats. The results indicate that chronic ethanol administration reduces formation of testosterone by affecting a step prior to pregnenolone. There may also be an effect on the conversion of some 3 beta-hydroxy-delta 5 to the corresponding 3-oxo-delta 4 steroids. Th...
Effects of Acute Alcohol Administration on Reproductive Endocrinology in the Male Rat
Alcoholism: Clinical and Experimental Research, 1978
The results of the current studies further document that acute alcohol administration markedly disrupts the function of the HPG in the male. Our results indicate that alcohol depresses serum testosterone levels and, thereby, produces clinical symptoms associated with hypoandrogenization. Moreover, our studies suggest that acute alcohol administration also affects the hypothalamic‐pituitary axis by reducing serum LH levels—an effect that may represent the primary action of alcohol on the HPG.
Plasma testosterone concentrations in alcoholics
Journal of studies on alcohol, 1976
Timo Leino 4 and Reino Ylikahri 5 SUMI•ARY, Plasma testosteroae concentrations were normal in 17 hospitalized alcoholics after a large dose of alcohol and in 16 Skid Row alcoholics. The findings fail to support the idea that the direc• effects o/ alcohol oa steroid metabolism cause gynecomastia and testicular atrophy.
Alcoholism: Clinical and Experimental Research, 1999
Teenage drinking continues to be a significant problem in the US., as well as abroad. We have previously demonstrated that opiate blockade with naltrexone, a drug currently used in patients to diminish alcohol craving, prevented the fall in serum testosterone seen after acute ethanol (EtOH) exposure in young, peripubertal male rats. To follow-up on this reversal, a series of experiments was performed to determine if naltrexone would also prevent the testosterone suppression caused by chronic EtOH exposure. Peripubertal rats either 45 days old (mid-pubertal) or 55 days old (late pubertal) were fed an EtOH-containing liquid diet or pair-fed control diet for 14 days. Each animal was implanted with either a naltrexone containing or placebo pellet before starting the liquid diet. In each age group, EtOH alone significantly suppressed testosterone, whereas naltrexone prevented this fall, although it had no effect alone. Serum luteinizing hormone was also suppressed by EtOH; however, naltrexone did not abrogate this fall. In the 45-day-old animals, P-luteinizing hormone mRNA levels rose significantly in the EtOH group, but not when naltrexone was coadministered with EtOH. There was no change in hypothalamic luteinizing hormone releasing hormone (LHRH) mRNA, pro-LHRH, or LHRH in any group at either age. Thus, naltrexone is able to partially prevent the EtOH-induced suppression of gonadal testosterone of young, adolescent male rats. This effect appears to be mediated directly at gonadal level, because hypothalamic and pituitary hormone changes were minor and nonsignificant.
Alcohol and the male reproductive system
Alcohol Research Health the Journal of the National Institute on Alcohol Abuse and Alcoholism, 2001
: hypothalamic-pituitary-gonadal axis; reproductive effects of AODU (alcohol and other drug use); male; reproductive system; testicles; nitric oxide; oxidation; ethanol-to-acetaldehyde metabolism; apoptosis; luteinizing hormone-releasing hormone; fertility; opioids MARY ANN EMANUELE, M.D., is a professor in