The Effects of Alcohol : Liver, Growth and Endocrine, Bones

by National Institute of Health

(Page 2 of 3)

Liver Effects

Elevated liver enzymes have been found in some adolescents who drink alcohol. Clark and colleagues found that adolescent alcohol use disorders were associated with higher gamma-glutamyl transpeptidase and alanine amino transferase. Moreover, young drinkers who also are overweight or obese exhibit elevated levels of serum ALT with even modest amounts of alcohol intake.

Growth and Endocrine Effects

In general, there has been a gradual decline in the onset of female puberty over the last century, at least when puberty is defined by age at menarche. Whether initiation of female puberty is continuing to decline and at what rate are the subjects of some debate. Much less information exists on pubertal development in males because of the greater difficulty in assessing developmental milestones. However, a recent study comparing data from two national surveys, one conducted between 1988 and 1994 and the other between 1963 and 1970, found that American boys from the later generation had earlier onset of some pubertal stages as measured by standard Tanner staging. Perhaps not surprisingly, early puberty - especially among girls - is associated with early use of alcohol, tobacco, and other drugs. In addition, alcohol use in early maturing adolescents has implications for normal growth and neuroendocrine development.

In both males and females, puberty is a period of activation of the hypothalamic-pituitary-gonadal axis. Pulsatile secretion of gonadotrophin-releasing hormone from the hypothalamus stimulates pituitary secretion of follicle-stimulating hormone and luteinizing hormone (LH) pulses, followed by marked increases in gonadal sex steroid output (estrogen and testosterone), which in turn increases growth hormone (GH) and insulin-like growth factor-1 (IGF-1) production. Data from several studies suggest that both androgens and estrogens stimulate GH production, but that estrogen controls the feedback mechanism of GH production during puberty even in males. The increase in these hormones not only promotes maturation of the gonads but also affects growth, muscle mass, and mineralization of the skeleton. Thus, alcohol consumed during rapid development (i.e., prior to or during puberty) has the potential to disrupt normal growth and endocrine development through its effects on the hypothalamus, the pituitary gland, and the various target organs such as the ovaries and testes.

Most human and animal research on alcohol and endocrine development has been conducted in females, but the limited data on both genders suggest that alcohol can have substantial effects on neuroendocrine function. Human studies have found that alcohol ingestion can lower estrogen levels in adolescent girls and lower both LH and testosterone levels in midpubertal boys. In both genders, acute alcohol intoxication produces a decrease in GH levels without significant change in either IGF-1 or insulin-like growth factor binding protein-3.

In female rats, alcohol has been shown to suppress the secretion of specific female reproductive hormones, thereby delaying the onset of puberty. Dees and colleagues found that immature female rhesus macaques exposed daily to alcohol (2 g/kg via nasogastric tube) exhibit lower levels of GH, FSH, LH, estradiol (E2), and IGF-1 (but not FSH or Leptin) compared with control subjects. Moreover, even though there was no effect on age of menarche in these animals, the interval between subsequent menstruations was lengthened, thereby interfering with the development of regular monthly cycles. Additional studies in rats have found that alcohol interferes with intraovarian systems, including IGF-1 and IGF-1 receptors; the nitric oxide (NO) system, and the steroidogenic acute regulatory protein, all of which combine to decrease estradiol secretion. Thus, alcohol not only disrupts the interaction between the brain, pituitary gland, and ovaries, it also directly impairs the regulatory systems within the ovaries.

In male rats, both acute and chronic alcohol exposure during adolescence results in a reversible suppression of serum testosterone. Evidence exists for involvement at the hypothalamic, pituitary, and gonadal levels, although the testes appear to be the prime target of alcohol's actions. Furthermore, GH levels are affected by acute and chronic alcohol exposure in male adolescent rats, whereas IGF-1, growth hormone releasing factor (GRF), and GRF mRNA content are variable, depending on the type of administration.

Thus, the data so far indicate that females who consume alcohol during early adolescence may be at risk for adverse effects on maturation of the reproductive system. Although in males the long-term effects of alcohol on reproductive function are unclear, the fact that GH as well as testosterone and/or estrogen levels are altered by alcohol in both genders may have serious implications for normal development because these hormones play a critical role in organ maturation during this stage of development.

Bone Density and Growth Effects

Only a handful of studies have examined the effects of adolescent drinking on bone development, with the most informative data thus far coming from animal research. Male rats chronically fed an alcohol liquid diet for 60 days encompassing the adolescent period (postnatal days 35 to 90) display limb length reduction and reduced metaphyseal and cortical bone growth in the limbs. These skeletal effects may be mediated through a reduction in osteoblast formation, which is associated with a decline in testosterone but not IGF-1. In addition, with abstinence, normal bone metabolism is not completely restored. Similarly, in female rats, Sampson and colleagues found that chronic alcohol consumption (4 weeks on an ethanol liquid diet) produces decreased limb length and reductions in cortical and cancellous bone, which are not fully reversed following cessation of drinking. Interestingly, female adolescent animals administered a binge model of drinking (i.e., 5 percent alcohol by gavage for either 2 or 5 consecutive days per week) show increased bone length, weight, and density, or no change, respectively. Human studies indicate an inverse relationship between alcohol consumption and bone mineral density in adolescent males, but not females. However, more studies are needed in humans and animals to get a clearer picture of alcohol's effects on bone growth in adolescents, particularly with respect to dose and pattern of consumption.

About the Author

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