The increase in alcohol (ALC) use and abuse by adolescents during recent years poses several risks for individuals associated with growth, endocrine functions and development. Puberty-related developmental problems can occur and often vary depending upon the age that consumption and abuse begins, as well as the frequency of use, amount consumed and the duration of these habits. In females, suppressed sex steroids and delayed breast development are early indicators of developmental problems, as well as delayed or altered menarche. Similarly, research using rhesus monkeys indicated prepubertal ALC consumption caused delayed development of a regular monthly pattern of menstruation. Importantly, it has been suggested that girls using ALC have four times the chances of having delayed puberty than non-users. These examples clearly indicate the health-related significance caused by ALC use during adolescence. Studies in prepubertal rats and rhesus monkeys reveal that ALC acts at the hypothalamic level to suppress key puberty-related genes and hormones, but more research is needed to define mechanisms behind these actions. The objective of this study is to obtain information which will allow us to better understand the detrimental effects and mechanisms of action of ALC on the female pubertal process and to begin to identify potential means by which we can ameliorate some of ALCs detrimental effects. To address mechanisms, critical assessments are needed as to the actions and interactions of ALC with regard to the control of hypothalamic luteinizing hormone releasing hormone (LHRH), the peptide responsible for pubertal onset and reproductive function thereafter. Puberty is the result of the increased excitatory activation of pulsatile LHRH release, while at the same time a decrease in the prepubertal inhibitory activity occurs that has been responsible for keeping a break on the pubertal process. Using prepubertal female rats, research in this proposal will employ in vivo and in vitro techniques with molecular and physiological approaches to identify and assess upstream excitatory and inhibitory hypothalamic genes and peptides that ultimately control prepubertal LHRH secretion, discern the puberty-related substances that regulate them, and define the actions and interactions of ALC on their expressions and physiological functions. Also, specific studies will assess potential means to effectively restore development and shorten the recovery time associated with prepubertal ALC use. This research is relevant to adolescent health and development and intended to further identify the effects of ALC with regard to brain events and their actions which control female pubertal maturation. Relevance Alcohol use and abuse by adolescents poses several risks for individuals associated with growth and the timing of puberty. More basic research is needed to better understand the mechanisms by which alcohol alters the pubertal process. This proposed research is important and relevant to adolescent health and development and is intended to further identify the effects of alcohol with regard to brain events and their actions which control female pubertal maturation.

Public Health Relevance

The increase in alcohol use and abuse by adolescents during recent years poses several risks for individuals associated with growth and endocrine development. Studies proposed will assess the involvement and activation of specific puberty-related genes and actions of peptides in the brain critical to the onset of puberty, discern the effects of ALC on their actions and interactions, and devise methods to effectively restore development and shorten the recovery time associated with delayed puberty due to prepubertal alcohol use. This research is important and relevant to adolescent health and development, and the information gained will promote a better understanding of the effects of alcohol on puberty-related events.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007216-28
Application #
9695139
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Murray, Gary
Project Start
1986-07-01
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2021-05-31
Support Year
28
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Texas A&M Agrilife Research
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
847205713
City
College Station
State
TX
Country
United States
Zip Code
77845
Hiney, Jill K; Srivastava, Vinod K; Vaden Anderson, Danielle N et al. (2018) Regulation of Kisspeptin Synthesis and Release in the Preoptic/Anterior Hypothalamic Region of Prepubertal Female Rats: Actions of IGF-1 and Alcohol. Alcohol Clin Exp Res 42:61-68
Srivastava, Vinod K; Hiney, Jill K; Dees, William L (2018) Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events. Alcohol Clin Exp Res 42:1166-1176
Hiney, Jill K; Srivastava, Vinod K; Dees, William L (2016) Manganese protects against the effects of alcohol on hypothalamic puberty-related hormones. Life Sci 148:106-11
Srivastava, Vinod K; Hiney, Jill K; Stevener, Kristyn et al. (2015) Differential Effects of Alcohol on Excitatory and Inhibitory Puberty-Related Peptides in the Basal Hypothalamus of the Female Rat. Alcohol Clin Exp Res 39:2386-93
Dees, W L; Hiney, J K; Srivastava, V K (2015) Alcohol alters hypothalamic glial-neuronal communications involved in the neuroendocrine control of puberty: In vivo and in vitro assessments. Alcohol 49:631-7
Hiney, Jill K; Srivastava, Vinod K; Volz, Claire E et al. (2014) Alcohol alters insulin-like growth factor-1-induced transforming growth factor ?1 synthesis in the medial basal hypothalamus of the prepubertal female rat. Alcohol Clin Exp Res 38:2572-8
Srivastava, Vinod K; Hiney, Jill K; Dees, William L (2014) Actions and interactions of alcohol and transforming growth factor ?1 on prepubertal hypothalamic gonadotropin-releasing hormone. Alcohol Clin Exp Res 38:1321-9
Srivastava, Vinod K; Hiney, Jill K; Dees, W Les (2011) Prepubertal ethanol exposure alters hypothalamic transforming growth factor-? and erbB1 receptor signaling in the female rat. Alcohol 45:173-81
Srivastava, Vinod K; Hiney, Jill K; Dees, W Les (2011) Hypothalamic glial-to-neuronal signaling during puberty: influence of alcohol. Int J Environ Res Public Health 8:2876-94
Srivastava, Vinod K; Hiney, Jill K; Dees, William L (2011) Hypothalamic actions and interactions of alcohol and IGF-1 on the expression of glial receptor protein tyrosine phosphatase-? during female pubertal development. Alcohol Clin Exp Res 35:1812-21

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