Effects of Acute Alcohol Administration on Reproductive Endocrinology in the Male Rat (original) (raw)
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.
Alcohol's Effects on Male Reproduction
Alcohol Health and Research World, 1998
: AODE (alcohol and other drug effects); hypothalamus; pituitary gland; male genitals; reproductive function; testosterone; hormone metabolism; heavy AOD use; cell type; luteinizing hormone; follicle stimulating hormone; gonadotropin RH; secretion; animal model; male; literature review article by Hiller-Sturmhöfel and Bartke, pp. 153-164.) Among other hormones, the hypothalamus produces gonadotropinreleasing hormone (GnRH). GnRH is MARY ANN EMANUELE, M.D., is a professor in the EMANUELE, M.A.; KIRSTEINS, L.; REDA, D.; EMANUELE, N.V.; AND LAWRENCE, A.M. In vitro effect of ethanol exposure on basal and GnRHstimulated LH secretion from pituitary cells. Endocrine Research 15:293-401, 1989. EMANUELE, M.A.; TENTLER, J.J.; REDA, D.; KIRSTEINS, L.; EMANUELE, N.V.; AND LAWRENCE, A.M. The effect of in vitro ethanol exposure on 201 LHRH release from perfused rat hypothalami. Endocrine Research 16:313-321, 1990. EMANUELE, M.A.; TENTLER, J.; EMANUELE, N.V.; AND KELLEY, M.R. In vivo effects of acute EtOH on rat α and β luteinizing hormone gene expression. Alcohol 8:345-348, 1991.
Alcohol and Alcoholism, 2002
The effects of acute alcohol intoxication (AAI) on the pituitary-gonadal axis hormones, and the possible contribution of pituitary-adrenal axis hormones, β-endorphin and prolactin to alcohol-induced dysfunction of pituitary-gonadal axis hormones were studied in adult men and women. Blood samples were drawn from adults of both sexes who arrived at the emergency department with evident behavioural symptoms of drunkenness (AAI) or from adult volunteers with nil consumption of alcohol (controls). Our results demonstrated that AAI produces a high increase in plasma prolactin, corticotropin (adrenocorticotropic hormone, ACTH), and cortisol in adults of both sexes, a decrease in luteinizing hormone levels only in men, an increase in dehydroepiandrosterone-sulphate (DHEAS) and a contradictory behaviour of testosterone according to gender, with increased plasma testosterone in women and a decrease in men. ACTH and prolactin correlated positively with cortisol, DHEAS and testosterone in women, which suggests that prolactin and ACTH could contribute to stimulated adrenal androgen production. In contrast, the decrease in testosterone and increase in β-endorphin in men suggests that AAI could have an inhibitory effect on testicular testosterone, perhaps mediated by β-endorphin. Our results suggest that the effect of alcohol on pituitary-gonadal axis hormones in humans could depend on the gender and degree of sexual maturity of the individual.
Hypogonadism precedes liver feminization in chronic alcohol-fed male rats
Hepatology, 2000
Men who chronically abuse alcohol may display a spectrum of endocrine abnormalities including hypogonadism and feminization, with elevated serum estradiol and low serum testosterone. We examined factors that may result in disruption of hepatic sex hormone homeostasis in alcoholfed male rats and possible consequences of such changes. Rats were fed alcohol-containing or isocaloric diets for 30, 60, and 90 days. In alcohol-fed rats, serum testosterone levels and hepatic activity of 2 androgen-dependent estrogen metabolizing enzymes were reduced (P F .05) at all times, as was activity of androgen receptor. There was also a significant early and progressive decrease in testes/body ratio in alcohol-fed rats. Compared with this early decrease in testosterone-related parameters, there was a significant increase in serum estrogen levels (at 30 and 90 days, 132% and 168% of control values, respectively). An increase in serum ceruloplasmin, an estrogen-responsive liver protein, was apparent at 60 and 90 days, but not at 30 days of alcohol exposure, suggesting that hypogonadism precedes liver feminization. Hepatic estrogen receptor activity was decreased in alcohol-fed rats at 60 and 90 days, the latter despite elevated serum estrogen levels. Hepatic aromatase was slightly increased in alcohol-fed rats, an elevation probably not sufficient to account for observed increases in serum estrogen. Taken together, these data suggest that (1) alcohol induces profound reduction of serum testosterone, resulting in loss of androgen-regulated hepatic functions such as estrogen-metabolizing enzyme activity and activity of androgen receptors; and (2) such alcohol-induced hypogonadism precedes changes in hepatic sex hormone homeostasis and subsequent feminization. (HEPATOLOGY 2000;31:
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...
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
Alcoholism: Clinical and Experimental Research, 2003
The interaction of alcohol and testosterone has long been of interest, mainly due to the effect of alcohol on aggression and sexual behavior. To date, there have been very few, if any, studies examining the effect of acute alcohol administration on testosterone concentrations in the brain. The administration of 1,1-dideuteroethanol ([1,1-2 H 2 ]ethanol) provided the opportunity to trace the deuterium label into newly synthesized deuterotestosterone in brain samples to determine whether ethanol oxidation was directly linked to testosterone synthesis.
Alcoholism: Clinical and Experimental Research, 1997
It is the purpose of this study to investigate the effects of acute ethanol (EtOH) on the female rat hypothalamic-pituitary-gonadal (HPG) axis. The molecular and cellular mechanistic details of such effects have been studied intensively in the male rat. However, there has been relatively little in-depth study of EtOH's effects on the adult, postpubertal female rat. Adult female rats with confirmed 4-or &day estrous cycles were given a single injection of EtOH or saline between noon and 1:00 PM on proestrous and were killed at 400 PM. EtOH caused a sharp 97% reduction in luteinizing hormone (LH) serum levels (p c 0.001), cornpared with controls with no concomitant change in LH mRNA EtOH also significantly reduced hypothalamic LH releasing hormone (LHRH) by 49% (p c 0.01), with no change in content of the precursor pro-LHRH compared with saline-injected controls. The ratio of LHRH to pro-LHRH was also significantly reduced by EtOH (p c 0.05), compared with control. There was no EtOH-induced change in LHRH mRNA Compared with saline, EtOH reduced both serum estradiol by 37% (p c 0.02) and progesterone by 47% (p c 0.001). These results show that EtOH has profound disruptive effects on the female HPG axis. Our data suggests that EtOH decreases the releasable LHRH pool either by decreasing conversion of pro-LHRH to LHRH andor by increasing local LHRH degradation. This acutely restricts the release of LH and subsequent estradol and progesterone secretion.
Notulae Scientia Biologicae, 2020
This study evaluated the influence of human chorionic gonadotropin on hormonal and haematological profile of postpubertal male albino rats exposed to chronic oral administration of alcohol. Twenty-four mature male albino rats were assigned to four groups (n=6). Group A was the control, given distilled water, Group B was given 30% ethanol (8 ml/kg) orally 3 times a week, Group C was given human chorionic gonadotropin (HcG) (50 IU/kg) subcutaneously 3 times a week and Group D was given HcG (50 IU/kg) subcutaneously + 30% ethanol (8 ml/kg) orally 3 times a week. The study was for 10 weeks, and hormonal profile and haematology were determined. The follicle stimulating hormone of Group B decreased significantly (P<0.05) when compared to Groups A, C and D. The luteinizing hormone was significantly lower (P<0.05) in Group B when compared to Groups A, C and D. The testosterone level was significantly higher (P<0.05) in Group D when compared to Groups A, B and C. The results obtaine...
Interaction of Ethanol and Nitric Oxide in the Hypothalamic-Pituitary-Gonadal Axis in the Male Rat
Alcoholism: Clinical and Experimental Research, 1998
Ethanol (EtOH) exerts deleterious actions on reproductive function at all three levels: the hypothalamus, pituitary, and gonad (HPG). Nitric oxide (NO), a newly identified messenger molecular in a variety of biological systems, has been suggested as playing a role in HPG hormone regulation. NO stimulates luteinizing hormone releasing hormone secretion from the hypothalamus and has variable effects on luteinizing hormone release from the pituitary. NO is inhibitory to testosterone production, and it may also directly inhibit some steroidogenic enzymes. Related studies in the accompanying paper have demonstrated that inhibiting NO synthase (NOS) using various NOS inhibitors can prevent the EtOH-induced suppression of testosterone on the male HPG axis, and this action is mainly, although not entirely, due to a direct gonadal effect. To further investigate the role of NO in the HPG axis, we assessed the HPG NO-NOS system by determining NOS mRNA levels, protein levels, and enzyme activity in the presence and absence of EtOH. At the testicular level, EtOH's action did not appear to be mediated by increasing NO content. However, EtOH was able to potentiate NO'S suppressive effect on the testicular synthesis system. One locus where EtOH and NO interacted was at the steroidogenic enzyme level. fl-nitro-L-arginine methyl ester, a NOS inhibitor, was found to antagonize the EtOHinduced fall on P-450 17a-hydroxylase/C17-20 lyase mRNA levels when administered along with EtOH. EtOH had no apparent effect on the pituitary NO-NOS system and its effects on the hypothalamic NO-NOS system do not explain its ability to reduce luteinizing hormone releasing hormone secretion.
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 &amp;lt; 0.05), a decrease in androstenedione (from 5.1 +/- 0.4 nmol/liter to 4.0 +/- 0.3 nmol/liter; p &amp;lt; 0.05), and an increase in the testosterone:androstenedione ratio (from 2.8 +/- 0.3 to 4.2 +/- 0.4; p &amp;lt; 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.
Endocrine, 1999
Teenage drinking continues to be a major problem in the United States as well as abroad. A significant depression in serum testosterone in adolescents who consume EtOH has been well described. In the male rodent model, a similar fall in testosterone has been reported, and prevention with the opiate blocker naltrexone has been demonstrated. To explore further the impact of chronic EtOH exposure on the reproductive axis in peripubertal rats, we designed this study specifically to define whether or not there was recovery after abstinence by examining reproductive hormones and their genes during and after EtOH exposure. Peripubertal male rats 35 d old were fed an EtOH-containing diet or a calorically matched control diet for 60 d. A third group was fed the control liquid diet ab libitum. EtOH was then withdrawn and all animals were fed standard rat chow and water ad libitum for an additional 3 mo. The EtOH-imbibing animals were found consistently to weigh less than their pair-fed mates and liquid diet ad libitum animals. Serum testosterone levels and testicular weights were significantly decreased by EtOH whereas serum estradiol levels were higher, suggesting enhanced peripheral conversion by EtOH. Spermatogenesis, assessed by histological parameters, was unaltered by EtOH. Serum luteinizing hormone levels were not different among the groups. Hypothalamic luteinizing hormone-releasing hormone mRNA levels were unaffected by EtOH. During the 3-mo recovery period, all the changes reversed, with a significant increase noted in testosterone. All other parameters remained the same among the groups. Thus, although chronic EtOH exposure in the peripubertal age period results in significant reproductive alterations, there is complete recovery on withdrawal.
Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females
Drug and Alcohol Dependence, 1988
During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers {aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1 -5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24 -46% compared to basal values. 5odihydrotestosterone levels decreased 23 -31%, androstendione and dehydroepiandrosterone-sulphate levels decreased 6 -48Oh1, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68%. Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.
Neurotoxicology and Teratology, 1998
exposure during the last week of gestation in the rat: Inhibition of the prenatal testosterone surge in males without long-term alterations in sex behavior. NEUROTOXICOL TERA-TOL 20 (4) [483][484][485][486][487][488][489][490] 1998.-In utero ethanol exposure decreases the prenatal testosterone (T) surge in male rats. To determine the functional significance of this suppression, we measured sex behavior in adult litter representatives of pregnant rats that were administered a fortified liquid diet containing 35% ethanol-derived calories from day 15 of gestation through parturition. Control dams were pair-fed an isocaloric liquid diet with the ethanol calories replaced by sucrose. Results from the behavioral studies showed that gonadally intact fetal alcohol-exposed (FAE) males exhibited little masculine sex behavior in the first of four weekly sessions. However, their behavior in the subsequent three tests was indistinguishable from pair-fed controls. Lordosis quotients in the same males following castration and estrogen and progesterone treatment were under 10%. In castrated FAE females, no effects of prenatal ethanol exposure were observed in masculine behaviors following androgen replacement or feminine sex behaviors following estrogen and progesterone replacement. Additional studies measured the duration of prenatal ethanol exposure necessary to inhibit the prenatal T surge in order to determine whether the inhibition was due to a direct effect of the drug. Results revealed an inhibition of the surge in males exposed to ethanol from days 14 through 20 of pregnancy, days 14 through 16 of pregnancy, or days 17 through 20 of pregnancy. A normal surge of T was observed on days 18-19 of gestation in control fetuses. These findings indicate that ethanol does not have to be present in blood at the time of the surge to have an inhibitory effect. They also reveal that the surge can be inhibited with as little as 24-36 h of ethanol exposure prior to its normal appearance on day 18 of gestation. In spite of this inhibition of the prenatal T surge, the behavioral results indicate that normal masculinization and defeminization of sex behavior occurs in FAE males exposed to ethanol after the beginning of the period of differentiation of the hypothalamus and testes. © 1998 Elsevier Science Inc. Prenatal alcohol Testosterone Rat Lordosis Sex behavior Masculinization Defeminization Prenatal testosterone surge Estrogen Progesterone PRENATAL ethanol exposure in the rat significantly decreases the prenatal testosterone (T) surge on days 18 and 19 of gestation in the male fetus (14,25) as well as the postnatal T surge occurring within 2-4 h after parturition (13). Evidence exists that disruption of the timing or occurrence of either surge can result in incomplete masculinization or defemi-nization of male sex behavior (9,28,35). In spite of the disruption of the prenatal testosterone surge by ethanol, results from studies of sex behavior in FAE males are inconsistent. Some investigators have found either decreased masculine behavior (27,29) or incomplete defeminization (10,29) in FAE males. Udani et al. (27) treated dams with a fortified Requests for reprints should be addressed to Robert F.
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...
Alcoholism: Clinical and Experimental Research, 1999
Thc cffects of ethanol (EtOH) and nitric oxide (NO) are well known in the adult male rat reproductive axis. In the prcsent study, we investigate the effects of EtOH, NO, and their interaction on key genes and rcproductivc hormone levcls in mid-(45-day) and latepubertal (55-day) male rats. Using three different NO synthasc blockers-N&-nitro-L-argininc methyl ester (L-NAME), NG-nitro-L-arginine (L-NA), and 7-nitroindazolc-we show that it is possible to block, in part, some of the disruptive effects of EtOH. L-NAME totally prevented the EtOH-induced fall in serum testosterone in both 45-and55-day-old rats ( p < 0.05 and p < 0,001, respectivcly). On the other hand, the D-NAME, an inactive isomer of L-NAME, did not protect testosterone from supprcssion caused by EtOH. Similarly, L-NA and 7-nitroindazole prevented the supprcssion of tcstosteronc caused by EtOH in 55-day-old animals ( p < 0.001 L-NA and p < 0.05 for 7-nitroindazole), but not in the 45-day-old rats. Serum luteinizing hormone (LH) was significantly reduced by EtOH in all the studics in both age groups. I.-NAME (but not D-NAME) and L-NA prevented this inhibition in 55-day-old animals ( p < 0.001 for L-NAME andp < 0.01 for L-NA). However, only L-NAwas ablc to prevcnt the effects of EtOH on LH in the 45-day-old rats. 7-Nitroindazole was unable to prevent the dccreasc in LH in either age group. Despite changes in the other reproductive hormones, there were no consistent changes in hypothalamic concentrations of either LH releasing hormone (LHRH) or its precursor. pro-LHRH. No treatment caused any change in steady-state levels of P-LH mRNA. There were no consistcnt changes in pro-LHRH mRNA; but, interestingly, in 45-day-old rats, L-NA given with or without EtOH lead to a significant fall in LHRH gene expression. Our findings indicate that the acute suppressive effects of EtOH on the hypothalamic-pituitary-gonadal axis of the purbertal male rat can be at least partially prevented by NO synthase blockade.
Alcoholism: Clinical and Experimental Research, 1993
Prenatal alcohol exposure in the rat is known to interfere with the neurobehavioral sexual differentiation of the male brain. Because normal sexual differentiation of the male brain requires adequate levels of perinatal testosterone, we examined the effect of prenatal ethanol exposure on (1) the postnatal surge of testosterone and (2) the in vitro secretion of testosterone in response to luteinizing hormone (LH) stimulation of testes from fetal alcohol exposed (FAE) animals and controls. Sprague-Dawley dams were administered a fortified liquid diet containing 35% ethanol-derived calories, a pairfed (PF) isocaloric liquid diet, or given ad libitum access to dry lab chow (CF). Dams were administered the liquid diets from days 7 or 14 through parturition. The postnatal surge of testosterone in FAE males was studied only in animals exposed to ethanol from day 14 through parturition. In the first experiment, FAE and PF males and females were delivered by cesarian section on day 22 of gestation (E22) and trunk blood collected at 0, 60, 120, and 240 min after parturition. Experiment 2 measured plasma testosterone in male pups that were killed at 0, 60, 120, 240, 360, and 480 min after delivery. Results showed that the postnatal testosterone surge of FAE males in both experiments was significantly attenuated compared with PF controls. No effect of prenatal ethanol was observed in female offspring. Female testosterone levels were several fold lower than male littermates, and no evidence of a postnatal testosterone surge was observed.
…, 1987
Plasma levels of LH, FSH, prolactin (PRL), and testosterone (T) were assessed in six normal men following administration of a pharmacologic dose of gonadotropin releasing hormone (GnRH) (500 I.tg iv over a one-rain period) with concomitant oral administration of either ethanol (0.695 g/kg of body weight over a 15-rain period) or ethanol placebo. Acute ethanol administration had no effect on the response of either LH or FSH to GnRH. PRL levels increased following GnRH and administration of both ethanol and ethanol placebo. Ethanol administration enhanced the T response to GnRH (p < 0.001 vs placebo). During the placebo condition, T levels did not rise significantly until 100 rain after GnRH administration, at which time the mean increment over baseline was 101 + 20 ng/dl (+ SEM). In contrast, following ethanol intake, T levels were significantly elevated within 30 rain after GnRH administration, at which time the mean increment over baseline was 187 + 42 ng/dl. The mean T increments were 304 + 62 and 472 + 77 ng/dl, respectively, 60 and 105 rain following GnRH and ethanol administration. The increase in T levels following acute ethanol intake and concomitant gonadotropin stimulation is in contrast to the well-documented effect of cttronic ethanol intake on suppression of testosterone synthesis by testicular Leydig cells.
Effect of alcohol on hormones in women
2001
Long-term effects of alcohol on estrogens and progesterone…………… 15 2.2.1.3 Acute effect of alcohol on androgens…………………………………… 2.2.1.4 Long-term effects of alcohol on androgens…………………………….. 2.2.1.5 Effect of alcohol on sex hormone-binding globulin (SHBG)…………… 2.2.1.6 Effect of alcohol on sex steroid synthesis in vitro……………………… 2.2.1.7 Effect of alcohol on sex steroid catabolism…………………………….. 2.2.2 Effect of alcohol on gonadotropins…………………………………………….. 2.2.3 Effect of alcohol on prolactin…………………………………………………… 2.2.4 Effect of alcohol on glucocorticoid steroids……………………………………. 2.2.4.1 Acute effect of alcohol on cortisol……………………………………… 2.2.4.2 Long-term effect of alcohol on cortisol………………………………… 2.2.4.3 Effect of alcohol on cortisol-binding globulin (CBG)…………………. 2.2.4.4 Effect of alcohol on glucocorticoid steroid catabolism…………………. 23 3 AIMS OF THE PRESENT STUDY…………………………………………………… 5 4 MATERIALS AND METHODS………………………………………………………. 4.1 Study subjects………………………………………………………………………… 4.2 Study procedures……………………………………………………………………. 4.3 Analytical procedures……………………………………………………………….. 4.4 Statistical methods…………………………………………………………………… 5 RESULTS……………………………………………………………………………… 5.1 Acute effect of alcohol on plasma androgen levels (II,IV,V)……………………….. 30 5.2 Acute effect of alcohol on urine androgen and glucocorticoid conjugates (IV,V)….. 5.3 Effect of long-term intake of alcohol on plasma androgens and urine androgen conjugates (V)………………………………………………………………………. 5.4 Acute effect of alcohol on plasma luteinizing hormone (II)…………………………. 5.5 Acute effect of alcohol on plasma estradiol, estrone, and ethinylestradiol (I,III)……. 5.6 Acute effect of alcohol on plasma progesterone (I)………………………………….. 36 5.7 Acute effect of alcohol on plasma prolactin (I)………………………………………. 5.8 Acute effect of alcohol on plasma cortisol (I)………………………………………… 5.9 Effect of long-term intake of alcohol on plasma cortisol and urine glucocorticoid conjugates (V)………………………………………………………………………… 5.10 Effect of oral contraceptives on hormone levels (I,II,IV)…………………………… 5.11 Plasma ethanol levels after intake of alcohol: effect of long-term alcohol intake and pretreatment with 4-methylpyrazole………………………………………………… 39 6 DISCUSSION………………………………………………………………………….. 6.1 Acute effects of alcohol on sex steroids……………………………………………… 6.1.1 Coupling of alcohol and sex steroid metabolism……………………………….. 6.2 Acute effect of alcohol on luteinizing hormone……………………………………… 44 6.3 Acute effect of alcohol on prolactin………………………………………………….. 6.4 Acute effects of alcohol on plasma cortisol and urine glucocorticoid conjugates…….. 45 6.5 Effect of long-term alcohol intake on plasma androgens…………………………….. 46 6.6 Effect of long-term alcohol intake on plasma cortisol……………………………….. 6.7 Effect of long-term alcohol intake on urine androgen and glucocorticoid conjugates.. 47 6.8 Effect of oral contraceptives on the hormonal balance………………………………..