The increase in alcohol (ALC) use and abuse by adolescents during recent years poses several risks for them associated with growth, endocrine functions and development. The overall goal 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. The studies proposed will assess influences of specific puberty related peptides, the involvement and activation of important genes critical to brain events leading to mammalian puberty, and discern the effects of ALC on their actions and interactions. In vivo and in vitro techniques using molecular and physiological approaches will be utilized following chronic and acute ALC exposure to address six aims which will collectively allow us to determine what factors are involved, the mechanisms of interference and potential means to reverse the detrimental effects of ALC on puberty related events.
Aim 1 will assess the effects of ALC on the synthesis of specific puberty related hypothalamic genes and proteins, with the results being correlated with hypothalamic, pituitary and ovarian hormones, as well as other indices of puberty.
Aim 2 will assess regulation of hypothalamic genes by peptides involved at puberty and determine the actions of ALC.
Aim 3 will assess the expression and regulation of glial and neuronal signaling-adhesion genes at puberty and determine the effects of ALC.
Aim 4 will assess the effects of ALC on the hypothalamic action of specific peptides that induce luteinizing hormone releasing hormone (LHRH) secretion at puberty.
Aim 5 will use cultured rat hypothalamic astrocytes and an LHRH neuronal cell line to further assess glial-neuronal mechanisms associated with LHRH secretion, determine the actions of ALC, and investigate potential means for reversal of ALC actions.
Aim 6 will test the ability of specific substances in vivo to protect against or reverse ALC-induced delayed puberty. This research, which is relevant to adolescent health and development, is intended to further identify consequences of ALC consumption with regard to hormonal events and their actions which can alter female pubertal maturation. Narrative The information gained from this study will allow us to better understand the detrimental effects and mechanisms of action of alcohol (ALC) on the female pubertal process. The studies proposed will assess influences of specific puberty related peptides, the involvement and activation of important genes critical to brain events leading to mammalian puberty, and discern the effects of ALC on their actions and interactions. This research, which is relevant to adolescent health and development, is intended to further identify consequences of ALC consumption with regard to hormonal events and their actions which can alter female pubertal maturation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007216-23
Application #
8266551
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Murray, Gary
Project Start
1986-07-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2014-04-30
Support Year
23
Fiscal Year
2012
Total Cost
$311,526
Indirect Cost
$97,419
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
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
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
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
Srivastava, Vinod K; Hiney, Jill K; Dees, William L (2014) Actions and interactions of alcohol and transforming growth factor β1 on prepubertal hypothalamic gonadotropin-releasing hormone. Alcohol Clin Exp Res 38:1321-9
Hiney, Jill K; Srivastava, Vinod K; Volz, Claire E et al. (2014) Alcohol alters insulin-like growth factor-1-induced transforming growth factor β1 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, W Les (2011) Prepubertal ethanol exposure alters hypothalamic transforming growth factor-α and erbB1 receptor signaling in the female rat. Alcohol 45:173-81
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-β during female pubertal development. Alcohol Clin Exp Res 35:1812-21
Dearth, Robert K; Delgado, David A; Hiney, Jill K et al. (2010) Parity-induced decrease in systemic growth hormone alters mammary gland signaling: a potential role in pregnancy protection from breast cancer. Cancer Prev Res (Phila) 3:312-21
Hiney, J K; Srivastava, V K; Les Dees, W (2010) Insulin-like growth factor-1 stimulation of hypothalamic KiSS-1 gene expression is mediated by Akt: effect of alcohol. Neuroscience 166:625-32
Srivastava, Vinod K; Hiney, Jill K; Dees, W Les (2009) Short-term alcohol administration alters KiSS-1 gene expression in the reproductive hypothalamus of prepubertal female rats. Alcohol Clin Exp Res 33:1605-14

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