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Alcohol and the Male Reproductive System
Mary Ann Emanuele, M.D., and Nicholas Emanuele, M.D.
Edited for legibility/clarity by: Narkissos
Alcohol use affects all three parts of the hypothalamic-pituitary-gonadal (HPG) axis, a system of endocrine glands and hormones involved in male reproduction. Alcohol use is associated with low testosterone and altered levels of additional reproductive hormones. Researchers are investigating several potential mechanisms for alcohol's damage. These mechanisms are related to alcohol metabolism, alcohol-related cell damage, and other hormonal reactions associated with alcohol consumption. Chronic alcohol use in male rats also has been shown to affect their reproductive ability and the health of their offspring. Key words: 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
The endocrine system, which is made up of several hormone-producing organs throughout the body, is integral to all normal body functions, including growth, development, metabolism, and reproduction. This article reviews research on the effect of alcohol use on the part of the endocrine system involved in male reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. This system of endocrine glands and hormones includes a brain region called the hypothalamus; the pituitary gland, located at the base of the brain; and the male gonads (testes). The article also highlights promising new strategies for preventing or reversing alcohol's harmful effects on the male reproductive system and describes research investigating the molecular mechanisms by which alcohol acts on this system.
OVERVIEW OF THE MALE REPRODUCTIVE SYSTEM
Of the three components of the HPG axis, the hypothalamus and the pituitary gland have solely regulatory functions, which are mediated by the hormones they produce and secrete, as described in the next paragraph. The third component-the testes-also produces key hormones, including testosterone, which control male sexual characteristics and behaviors. In addition, the testes are responsible for sperm production.
The hypothalamus produces luteinizing hormone-releasing hormone (LHRH), which is released in pulses into a system of blood vessels that connect the hypothalamus and the pituitary gland. In response to the LHRH signal, the pituitary gland produces two protein hormones called gonadotropins. These two gonadotropin hormones-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)-are then released into the body's general circulation and act primarily at the level of the gonads. In males, LH stimulates testosterone production from specialized cells called Leydig cells. FSH is important to sperm maturation in another compartment of the testes, the epididymis. Testosterone circulates in the blood back to the hypothalamic-pituitary unit and regulates the further production and secretion of LHRH and LH. When the system is functioning normally, a low testosterone level results in a rise in pituitary gonadotropins. Prolactin, a third reproductive hormone synthesized in the pituitary gland, is important to normal LHRH synthesis and secretion.
Synopsis of Figure 1: The hypothalamic-pituitary-gonadal axis. The hypothalamus produces luteinizing hormone releasing hormone (LHRH), which is released to the pituitary gland. In response to the LHRH signal, the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In males, LH stimulates testosterone production and FSH is important to sperm maturation. Testosterone circulates in the blood back to the hypothalamic-pituitary unit and regulates the further production and secretion of LHRH and LH.
NOTE: + = stimulatory effect; - = inhibitory effect.
Low levels of testosterone (i.e., hypogonadism) in adult men have been associated with a variety of medical problems including accelerated osteoporosis, decreased muscle and prostate function, anemia, altered immune function, and decreased reproductive ability (Klein and Duwall 1994; Jackson and Klerekoper 1990; Azad et al. 1991; Berczi et al. 1981; Hadley 1988). Each of these conditions can cause significant health problems. These effects of low testosterone are greater in adult men who have had low testosterone levels since adolescence compared with adult men who experience diminished testosterone levels only in adulthood (Hadley 1988; Yen and Jaffe 1991). An adolescent or teenager who experiences short-term, intermittent decreases in testosterone or permanent hypogonadism is predisposed to experience these problems later in life.
Research with animals has consistently demonstrated an association between both acute (i.e., one time, one occasion) and chronic (i.e., long-term) alcohol consumption and low testosterone. As testosterone levels decrease, levels of LH and FSH would be expected to increase to stimulate the production of more testosterone. However, studies with young (i.e., pubertal) male rats indicate that both acute and chronic alcohol exposure result in profound testosterone suppression accompanied by lower or normal LH and FSH levels, when elevated levels are expected (Hadley 1988; Yen and Jaffe 1991). This suggests that the hypothalamic cells which produce LHRH do not function correctly when the feedback normally provided by testosterone is removed (i.e., when testosterone levels decrease). Thus it appears that alcohol's damaging effects on reproduction are mediated at all three levels of the male reproductive unit: the hypothalamus, pituitary, and testes.
Mary Ann Emanuele, M.D., and Nicholas Emanuele, M.D.
Edited for legibility/clarity by: Narkissos
Alcohol use affects all three parts of the hypothalamic-pituitary-gonadal (HPG) axis, a system of endocrine glands and hormones involved in male reproduction. Alcohol use is associated with low testosterone and altered levels of additional reproductive hormones. Researchers are investigating several potential mechanisms for alcohol's damage. These mechanisms are related to alcohol metabolism, alcohol-related cell damage, and other hormonal reactions associated with alcohol consumption. Chronic alcohol use in male rats also has been shown to affect their reproductive ability and the health of their offspring. Key words: 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
The endocrine system, which is made up of several hormone-producing organs throughout the body, is integral to all normal body functions, including growth, development, metabolism, and reproduction. This article reviews research on the effect of alcohol use on the part of the endocrine system involved in male reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. This system of endocrine glands and hormones includes a brain region called the hypothalamus; the pituitary gland, located at the base of the brain; and the male gonads (testes). The article also highlights promising new strategies for preventing or reversing alcohol's harmful effects on the male reproductive system and describes research investigating the molecular mechanisms by which alcohol acts on this system.
OVERVIEW OF THE MALE REPRODUCTIVE SYSTEM
Of the three components of the HPG axis, the hypothalamus and the pituitary gland have solely regulatory functions, which are mediated by the hormones they produce and secrete, as described in the next paragraph. The third component-the testes-also produces key hormones, including testosterone, which control male sexual characteristics and behaviors. In addition, the testes are responsible for sperm production.
The hypothalamus produces luteinizing hormone-releasing hormone (LHRH), which is released in pulses into a system of blood vessels that connect the hypothalamus and the pituitary gland. In response to the LHRH signal, the pituitary gland produces two protein hormones called gonadotropins. These two gonadotropin hormones-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)-are then released into the body's general circulation and act primarily at the level of the gonads. In males, LH stimulates testosterone production from specialized cells called Leydig cells. FSH is important to sperm maturation in another compartment of the testes, the epididymis. Testosterone circulates in the blood back to the hypothalamic-pituitary unit and regulates the further production and secretion of LHRH and LH. When the system is functioning normally, a low testosterone level results in a rise in pituitary gonadotropins. Prolactin, a third reproductive hormone synthesized in the pituitary gland, is important to normal LHRH synthesis and secretion.
Synopsis of Figure 1: The hypothalamic-pituitary-gonadal axis. The hypothalamus produces luteinizing hormone releasing hormone (LHRH), which is released to the pituitary gland. In response to the LHRH signal, the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In males, LH stimulates testosterone production and FSH is important to sperm maturation. Testosterone circulates in the blood back to the hypothalamic-pituitary unit and regulates the further production and secretion of LHRH and LH.
NOTE: + = stimulatory effect; - = inhibitory effect.
Low levels of testosterone (i.e., hypogonadism) in adult men have been associated with a variety of medical problems including accelerated osteoporosis, decreased muscle and prostate function, anemia, altered immune function, and decreased reproductive ability (Klein and Duwall 1994; Jackson and Klerekoper 1990; Azad et al. 1991; Berczi et al. 1981; Hadley 1988). Each of these conditions can cause significant health problems. These effects of low testosterone are greater in adult men who have had low testosterone levels since adolescence compared with adult men who experience diminished testosterone levels only in adulthood (Hadley 1988; Yen and Jaffe 1991). An adolescent or teenager who experiences short-term, intermittent decreases in testosterone or permanent hypogonadism is predisposed to experience these problems later in life.
Research with animals has consistently demonstrated an association between both acute (i.e., one time, one occasion) and chronic (i.e., long-term) alcohol consumption and low testosterone. As testosterone levels decrease, levels of LH and FSH would be expected to increase to stimulate the production of more testosterone. However, studies with young (i.e., pubertal) male rats indicate that both acute and chronic alcohol exposure result in profound testosterone suppression accompanied by lower or normal LH and FSH levels, when elevated levels are expected (Hadley 1988; Yen and Jaffe 1991). This suggests that the hypothalamic cells which produce LHRH do not function correctly when the feedback normally provided by testosterone is removed (i.e., when testosterone levels decrease). Thus it appears that alcohol's damaging effects on reproduction are mediated at all three levels of the male reproductive unit: the hypothalamus, pituitary, and testes.
