Date Published: , 2017
Publisher: National Institute on Alcohol Abuse and Alcoholism
Author(s): Nadia Rachdaoui, Dipak K. Sarkar.
Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body’s most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic–pituitary–adrenal axis, the hypothalamic–pituitary–gonadal axis, the hypothalamic–pituitary–thyroid axis, the hypothalamic–pituitary–growth hormone/insulin-like growth factor-1 axis, and the hypothalamic–posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol’s effects on various components of the endocrine system and their consequences.
The hypothalamic–pituitary axis can be considered the coordinating center of the endocrine system. The hypothalamus is the main neural control center, also known as the “master switchboard,” which coordinates nervous and endocrine system functions. The hypothalamus consolidates inputs derived from higher brain centers, various environmental cues, and endocrine feedback. Neurons within the hypothalamus produce and secrete releasing hormones, such as corticotropin-releasing factor (CRF), luteinizing hormone–releasing hormone (LHRH), thyrotropin-releasing hormone (TRH), and growth hormone–releasing hormone (GRH), as well as inhibiting hormones, such as somatostatin and dopamine, directly into the blood vessel connecting the hypothalamus with the pituitary gland (i.e., the hypothalamic– hypophyseal portal vein). These hormones then control the synthesis and release of hormones in the pituitary gland. The pituitary gland comprises two sections—the adenohypophysis, or anterior lobe, and the neurohypophysis, or posterior lobe. In response to signals from the hypothalamus, the anterior pituitary produces and secretes trophic hormones, which are hormones that have a growth effect on the organs or tissues they are targeting. They include, among others, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and growth hormone (GH) and modulate the functions of several peripheral endocrine glands (i.e., adrenal glands, thyroid, and gonads) and tissues (e.g., breast, muscle, liver, bone, and skin) (see the table).
The HPP axis includes two neuropeptides—AVP and oxytocin—both of which are produced by cells whose cell bodies are located in the hypothalamus but that extend to the posterior pituitary, where they release their hormones. AVP can be produced by two types of cells (i.e., magnocellular and parvocellular cells). Magnocellular neurosecretory cells produce the AVP that is found in peripheral blood. This AVP is secreted in response to osmotic stimuli and is involved in regulating the concentration of dissolved molecules (i.e., osmolality) in the body fluids by retaining water in the body and constricting blood vessels (Iovino et al. 2012; Verbalis 1993). In contrast, AVP produced by the parvocellular system is secreted following psychological stress and is involved in potentiating the action of CRF on ACTH release (Romero and Sapolsky 1996). Some AVP also may be released directly into the brain, and accumulating evidence suggests it plays an important role in social behavior, sexual motivation and pair bonding, and maternal responses to stress (Insel 2010). In the context of chronic alcohol use, AVP is involved in the disturbed water balance observed in actively drinking people with AUD and during acute withdrawal (Döring et al. 2003; Ehrenreich et al. 1997). AVP also may affect cognitive function, because treatment of alcoholic patients with memory deficits by using AVP analogs resulted in improved cognitive performance (Laczi 1987). Finally, studies in rodents have suggested that AVP may play a role in the development and maintenance of alcohol tolerance (Hoffman 1994).
Alcohol’s deleterious effects on the endocrine system have far-reaching consequences that can result in serious physiological and behavioral disorders. Alcohol abuse not only causes hormonal disturbances, but because these disturbances permeate every organ and tissue in the body, can result in various debilitating disorders, such as stress intolerance, disturbed water balance and body osmolality, reproductive dysfunction, thyroid problems, immune abnormalities, diabetes, cardiovascular disease, cancer, and psychological and behavioral disorders. The different components of the endocrine system, particularly the HPA axis, HPG axis, HPT axis, GH/IGF-1 axis, and HPP systems, normally communicate with each other as well as with the nervous and immune systems in response to external environmental cues and help maintain homeostasis and health. These coordinated bidirectional interactions rely on the production and release of chemical messengers, such as neurotransmitters, hormones, and cytokines, that mediate the communications between the different systems. Alcohol abuse disrupts the release of these chemical signals and negatively affects the communication pathways. A better understanding of the mechanisms involved in alcohol’s effects on the bidirectional interactions between the HPA, HPG, HPT, and GH/IGF-1 axes; the HPP system; and the immune system will help pave the way for the development of effective therapeutic tools for AUD.