Elaine Rosenblum

Lipid peroxidation: A mechanism for alcohol-induced testicular injury☆

That alcohol abuse may lead to testicular lipid peroxidation is suggested by the fact that ethanol is a known testicular toxin and its chronic use leads to both endocrine and reproductive failure. Because testicular membranes are rich in polyenoic fatty acids that are prone to undergo peroxidative decomposition, it is reasonable to consider that lipid peroxidation may contribute to the membrane injury and gonadal dysfunction that occurs as a result of alcohol abuse and/or chronic use. The present report reviews the studies supporting the concept that testicular lipid peroxidation is a metabolic consequence of chronic alcohol administration to animals and that its presence correlates with the gonadal injury present in animals ingesting ethanol for prolonged periods. Consistent with such a mechanism for putative alcohol-associated testicular toxicity are the observed reductions in the testicular content of polyenoic fatty acids and glutathione (GSH) content of the testes of alcohol-fed animals as compared to isocalorically fed controls. The later finding demonstrates that ethanol modifies the precarious antioxidant balance of testicular tissue such that enhanced peroxidation can occur. It is well known that peroxidation injury can be attenuated when it occurs in association with dietary vitamin A supplementation. Thus, it is of interest to note that vitamin A, acting as an antioxidant, stabilizes testicular membranes by reducing lipid peroxidation and prevents the alcohol-induced atrophy that occurs in animals not receiving vitamin-A-enriched diets. Taken together, these observations suggest that the enhanced peroxidation of testicular lipids that occurs following ethanol exposure may be an important factor in the pathogenesis of alcohol-associated gonadal injury.

Selective fetal malnutrition: The effect of ethanol and acetaldehyde upon in vitro uptake of alpha amino isobutyric acid by human placenta

Abstract Uptake of alpha amino isobutyric acid was measured in human placental villus tissue exposed in vitro to ethyl alcohol (ethanol) (0.3 g/dl–2 g/d1) or acetaldehyde (50 μM-20 mM). Ethanol and acetaldehyde significantly inhibited uptake of amino acid at higher, pharmacologic concentrations (2 g/dl and 2–20 mM respectively). Inhibition by 10 mM acetaldehyde was partially reversible. The results suggest that the human placenta is resistant to acute ethanol-associated effects upon amino acid transport in vitro . However, both ethanol and its major circulating metabolite, acetaldehyde, may still alter placental function during in vivo chronic exposure.

Predictors of Postmenopausal Body Mass Index and Waist Hip Ratio in the Oklahoma Postmenopausal Health Disparities Study

Objective: The goal of the current study has been to examine systematically the respective roles of nutrition, exercise, menopausal weight gain, moderate drinking and smoking as determinants of body mass index (BMI) and waist hip ratio (WHR) in a setting in which the role of race or ethnic group could be simultaneously or individually evaluated as predictors of BMI and WHR. Because the use of estrogen replacement has been reported to affect estimates of body fat mass in postmenopausal women, endocrine factors have also been evaluated. Methods: The design is cross-sectional with historical prospective elements. The study has a biomedical focus and is not an epidemiologic study. Data are from 649 women recruited into The Postmenopausal Health Disparities Study in Oklahoma. The study population was composed of 649 postmenopausal women: American Indian: 226 (34.9%), Asian: 21 (3.2%), Black: 78 (12.0%), Hispanics: 54 (8.3%) and Whites: 270 (41.6%). Recruitment occurred between 1994 and late 1999 in Oklahoma. Results: In this multi-racial, multi-ethnic study population, there was statistical heterogeneity in all nutrition/dietary and exercise variables as well as in other potential determinants of BMI and WHR. In contrast to the literature available for postmenopausal women in which postmenopausal status, estrogen replacement and race have rarely been taken into account, the results of multi-linear regression revealed the following: Significant predictors for BMI, with or without WHR specified, included the neuroendocrine factors, menopausal weight gain, smoking, mean fitness (i.e., difficulty performing physical activities), fat as percent of total calories, moderate drinking and being Asian or Black. When WHR was not included, total calories and socioeconomic status also entered the model. The statistical predictors of WHR in the total study population with BMI in the equation included BMI and the neuroendocrine variables of FSH, E2, but not ERT, as well as the interaction of higher intensity exercise fitness with frequency, socioeconomic status and being American Indian or Asian. When BMI was not included in the model, in addition to the neuroendocrine factors, the interaction of lower intensity exercise fitness with frequency, fat as percent of total calories, age living alone and being American Indian or and Black were significant predictors of WHR. The predictors of both BMI and WHR were found to differ among individual racial and ethnic groups. Conclusions: Given the role of increased body fat and obesity in disease risk and the substantial differences in life expectancy among the racial and ethnic groups, the findings of this study, particularly in contrast to literature reports, strongly suggest that a whole variety of factors including hormonal status and race need to be considered when examining the role of dietary factors and physical activity in relation to estimates of body fat mass and disease risk.

Effects of Ethanol on Endocrine Cells: Testicular Effects

Ethanol has been shown to produce a wide variety of endocrine effects involving such organs as the hypothalamus and the pituitary, gonadal, adrenal, and thyroid glands. Of these the best studied are those that involve the hypothalamic-pituitary-gonadal axis and particularly the testes. Thus ethanol ingestion by man and experimental animals has been shown to reduce plasma testosterone levels and if continued in a chronic fashion to be associated with the development of overt testicular atrophy. The following is a presentation of the morphologic and biochemical consequences of alcohol ingestion by rats initiated in an effort to understand the mechanisms responsible for alcohol-associated testicular dysfunction observed clinically in chronically alcoholic men.

The effect of portal-systemic shunting on hepatic sex hormone receptors in male rats

Signs of feminization are seen in men with cirrhosis of alcoholic but also of nonalcoholic origin even in the absence of markedly increased plasma estrogen levels. Recently identified alterations of hepatic sex hormone receptor levels have provided a hypothetical mechanism for the pathogenesis of the feminization seen in cirrhotic men. The aim of the present study was to determine the effect of experimental portal-systemic shunting in adult male rats on hepatic sex hormone receptor levels, plasma sex hormones, and two markers for sex hormone action in the liver. The following alterations were found in male rats with surgically created portacaval shunts compared with sham-operated controls: the hepatic content of cytosolic estrogen receptors was reduced by 35% and the cytosolic androgen receptors content by 59%; plasma levels of estradiol increased 6.7-fold while those of testosterone were reduced by 71%; the estrogen-responsive ceruloplasmin levels were decreased by 31% and the androgen-responsive male-specific estrogen binder by 72%. Based on these data, it can be concluded that portal-systemic shunting reduces the hepatic cytoplasmic content of several sex hormone related proteins. These changes are paralleled by a decreased estrogen responsiveness of the liver, as evidenced by the plasma ceruloplasmin level.

Alcohol Effects in Postmenopausal Women

The subject of alcohol effects in postmenopausal women encompasses three areas of conceptualization: The issue ofalcoholincludes both levels of consumption of alcoholic beverages as well as the alcohol and congener substances contained in alcoholic beverages. The termeffectsrequires specification; the material to be discussed in this chapter will be related to endocrine effects as manifested in changes in hormone levels and their interrelationships. The termpostmenopausalrequires definition, as the endocrine changes to be discussed are menopause-specific and are not applicable to women during their reproductive years.

Hidden Hormones in Alcoholic Beverages

Visualize the reproductive endocrinopathies and the subdysfunctional alterations of reproductive hormone homeostasis associated with abuse and use of alcoholic beverages. Now, mentally disassociate these endocrine effects from an alcohol etiology, and try to imagine an entirely different causal agent. Picture a quintessential alcoholic compensated-cirrhotic male with all extremes of endocrinopathy. He is both hypogonadal and feminized. He has gynecomastia and spider angiomata; he has reduced beard growth and a female escutcheon; his testes are atrophied, and he cannot achieve an erection; his levels of sex-hormone binding globulin are elevated, but his steroid estrogen levels are only minimally increased; his testosterone levels are below the lower limit of normal, but his gonadotropin levels are only mildly increased, rather than being substantially elevated in response to the low testosterone levels. Now reorient: Imagine this man to have a different face; cross out the word “alcohol” every place it appears in the history on the chart; pen a tentative diagnosis of “findings consistent with prolonged and sustained exposure to estrogen.”