The Hormonal Effects of Alcohol Use on the Mother and Fetus Kara Gabriel, M.A., Candace Hofmann, M.A., Maria Glavas, B.Sc., and Joanne Weinberg, Ph.D. During pregnancy, the hormonal systems of the mother and fetus are intricately interconnected to ensure normal fetal development. Accordingly, maternal alcohol consumption during pregnancy can interfere with fetal development, not only directly, through adverse effects exerted by alcohol that crosses the placenta and enters the fetal bloodstream, but also indirectly, by disturbing the functions and interactions of maternal and fetal hormones. In both the mother and the fetus, alcohol exposure can impair the functioning of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress; the hypothalamic-pituitary-gonadal axis, which controls reproductive functions; and the hypothalamic-pituitary-thyroid axis, which regulates the metabolism of almost all tissues. In addition, alcohol can interfere with the activities of growth hormone and insulin-like growth factors, which promote body growth and activity. Some of the effects of maternal alcohol consumption on fetal hormone systems may contribute to the adverse effects observed in children with fetal alcohol syndrome and related disorders. KEY WORDS: AODE (alcohol and other drug effects); gestation; mother; fetus; fetal development; polypeptide hormones; adverse drug effect; prenatal alcohol exposure; fetal alcohol syndrome; placenta; pituitary-adrenal axis; pituitary-thyroid axis; hypothalamus-pituitary axis; somatotropin; growth promoting factors; insulin; congenital anomaly; animal model; literature review he endocrine (i.e., hormonal) the activities of all components of the the amount of data from human subjects system plays a critical role in endocrine system by acting either continues to grow, research using animal Tmaintaining the body’s internal directly on the endocrine glands and/ models of prenatal alcohol exposure equilibrium (i.e., homeostasis). Through or on the hypothalamus or pituitary. has greatly expanded scientific under- the release of hormones, the endocrine In a pregnant woman, alcohol- standing of alcohol’s effects on endo- system regulates functions as diverse as induced alterations in endocrine activity crine function. reproduction, stress response, meta- may affect not only her health but also bolism, growth, and behavior. Two her ability to maintain a successful structures—(1) a brain region called pregnancy. Moreover, alcohol consump- The Role of the Placenta the hypothalamus and (2) the pituitary tion during pregnancy can directly affect gland, which is attached to the base of fetal development because alcohol read- During pregnancy, the placenta plays the brain through the pituitary stalk— ily crosses the placenta. Finally, alcohol a pivotal role in maintaining pregnancy work together to control the activity of consumed during pregnancy may alter and affecting fetal development. Until most endocrine glands in the body, includ- fetal development indirectly by disrupt- the fetal endocrine system is func- ing the adrenal glands, gonads (i.e., ing the normal hormonal interactions tional, the placenta acts as a miniature ovaries and testes), and thyroid gland. In between the mother and the fetus. This endocrine system, producing hormones turn, each of those glands produces one article reviews the multiple hormonal such as human chorionic gonadotropin, or more hormones (e.g., cortisol, estro- effects of alcohol use during pregnancy chorionic thyrotropin, and chorionic gen, testosterone, and thyroid hormone) on the mother and fetus. The article corticotropin. Through its hormone that control various physiological incorporates findings from both human production, the placenta regulates activities in the body. Alcohol can alter and animal studies, because although fetal growth, maturation, and nutrient 170 Alcohol Health & Research World Hormonal Effects of Alcohol on the Mother and Fetus utilization. In addition to its endocrine pregnancy and providing support for activity, the placenta acts as a partial Mechanisms of Alcohol- the fetus. Any disruption of the mater- barrier, or filter, between the maternal nal hormone balance can lead to poor and fetal blood, allowing the transfer Induced Changes in pregnancy outcome, including fetal birth of some maternal hormones and other Hormone Levels defects. As the following sections de- substances (e.g., alcohol) from the scribe, alcohol can interfere with mater- mother to the fetus while preventing The concentration of a given nal endocrine functions through numer- the transfer of others. As a result of hormone in the blood depends ous mechanisms (also see textbox). these placental functions, the fetus is on many factors, including the exposed to three sets of hormones: (1) rate at which the hormone is Effects on the Hypothalamic- those secreted by the placenta, (2) those produced and secreted, its distri- Pituitary-Adrenal Axis produced by the mother, and (3) the bution in the body, and the rate fetus’s own hormonal secretions. at which it is removed from the The hypothalamic-pituitary-adrenal Alterations in placental functioning, blood. Alcohol can interfere with (HPA) axis is a hormone system that plays including the production and activity of a hormone’s function by altering an essential role in the body’s response placental hormones, may affect fetal each of those factors. In addition, to stressful events (see table, p. 172). growth and development and increase total hormone concentration During periods of stress, the hypothal- the risk of spontaneous abortion. To does not necessarily correspond amus secretes corticotropin-releasing date, little information is available on the to the concentration of active hormone (CRH), which, in turn, stim- direct effects of alcohol on the placental hormone in the blood, because ulates the release of adrenocorticotropic hormones in humans. Animal models proteins called binding proteins, hormone (ACTH) from the pituitary have extended researchers’ limited under- or globulins, may attach to and gland. ACTH regulates the growth and standing of the placenta’s role in the temporarily inactivate a hormone. activity of the outer layer of the adrenal effects of prenatal alcohol exposure. Alcohol also may alter the levels glands (i.e., the adrenal cortex) and of these proteins, thereby modi- induces the secretion of adrenal hor- fying endocrine activity and, dur- mones called glucocorticoids—cortisol Alcohol’s Impact on ing pregnancy, inducing complex (in humans) and corticosterone (in Endocrine Functioning consequences for both mother rodents). As the glucocorticoid levels in Pregnant Women and fetus. increase in the blood, they act on the pituitary, hypothalamus, and other Historically, alcohol research in humans brain regions to inhibit further activa- has been conducted primarily in men. alcohol’s effects on neuroendocrine tion of the HPA axis. This process of Only during the past two decades have function in women, see Mello et al. inhibiting further hormonal activation researchers begun to analyze alcohol’s 1993). Studies have found that women is called negative feedback. effects on women (for a review of have higher blood alcohol levels (BALs) In the short term, glucocorticoids than men after drinking the same mobilize the body’s energy resources to amount of alcohol per body weight. In respond to stress. This mobilization KARA GABRIEL, M.A., and CANDACE addition, women show an accelerated occurs at the expense of energy-dependent HOFMANN, M.A., are doctoral students in progression of alcohol-related adverse functions, such as digestion, growth, the Department of Psychology and MARIA consequences, developing alcohol- and reproduction. When the stressful GLAVAS, B.SC., is a doctoral student in the induced liver disease and brain damage situation is prolonged (i.e., lasts for Graduate Program in Neuroscience, earlier in life and after lower alcohol weeks or months) or occurs frequently, University of British Columbia, Vancouver, intake than men (for a review, see the resulting metabolic effects and redis- British Columbia, Canada. All three stu- Roman 1988). The reasons for the tribution of resources may have patholog- dents are pursuing their dissertation research differential risks associated with alco- ical consequences, including the devel- in the laboratory of Joanne Weinberg, Ph.D. hol consumption for women and men opment of ulcers, growth retardation remain poorly understood, emphasiz- and underdevelopment (i.e., dwarfism) JOANNE WEINBERG, PH.D., is a professor ing the importance of further studies in children, and suppression of the in the Department of Anatomy and an on alcohol’s impact on physiological immune system. Alcohol consumption Honorary Professor in the Department of functioning in women. also activates the HPA axis and stimu- Psychology, University of British Columbia, Even fewer studies have investigated lates glucocorticoid release, similar to Vancouver, British Columbia, Canada. the consequences of alcohol consump- the effects of stress. (For more informa- tion during pregnancy on women’s tion on alcohol’s effects on the HPA This work was supported in part by National physiological (including endocrine) axis, also see the article by Gianoulakis, Institute on Alcohol Abuse and Alcoholism functions. The maternal endocrine pp. 202–210). grants AA–07789 to Joanne Weinberg system undergoes numerous changes The basal or resting activity of the and F31 AA–05499 to Kara Gabriel. that