In humans, excess alcohol intake often causes reproductive abnormalities including infertility and loss of libido. Some alcoholic men also shown evidence of gynecomastia. These pathological conditions in many human alcoholics are secondary to elevated levels of plasma prolactin (PRL), a condition known as hyperprolactinemia. Owe chronic alcohol intake induces hyperprolactinemia is not yet established. The present proposal will address this issue by studying the actions of ethanol on PRL secreting lactotropic cells in the pituitary gland of rats.
Three specific aims are proposed for addressing this interest.
Specific Aim 1 is to evaluate the action of ethanol on lactotropic cell proliferation and PRL secretion. Preliminary data indicated that ethanol administration using liquid diet for two weeks elevates blood ethanol levels to 0.1 mg/dl and promotes estrogen-induced lactotropic cell proliferation in Fischer 344 rats.
The aim of this study is to confirm these data and to further characterize the time-course of ethanol action on lactotropic cell's growth and secretion.
Specific Aim 2 is to determine the site of action of ethanol. Our working hypothesis is that ethanol effects lactotropic cell proliferation by acting at the level of pituitary. This possibility will be tested by determining the action of ethanol on PRL synthesis and secretion and cell proliferation in the primary cultures of enriched lactotropes.
Specific Aim 3 is to elucidate the mechanisms by which ethanol enhances lactotropic cell proliferation. The working hypothesis is that ethanol increases lactotropic cell proliferation and secretion by preventing expression of the growth-inhibitory peptide transforming growth factor B1 (TBF-B1) in the pituitary gland. This hypothesis will be tested by I) characterizing ethanol-induced changes of TGF-B1 and TGF-B type II receptor in the pituitary; ii) determining the effect of ethanol on TGF-B1 secretion from the lactotropic cells in primary cultures; iii) evaluating whether ethanol-induced lactotropic cell growth and secretion is altered following overexpression or repression of TGF-B1 and it's TGF-B type II receptor in these cells. The proposed research will yield an increased understanding of ethanol effects on prolactinomas and hyperprolactinemia. Such knowledge should help to better manage these neuroendocrine diseases in alcoholic patients.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
7R01AA011591-02
Application #
2894205
Study Section
Special Emphasis Panel (ZRG4-ALTX-3 (01))
Project Start
1998-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Rutgers University
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Jabbar, Shaima; Reuhl, Kenneth; Sarkar, Dipak K (2018) Prenatal alcohol exposure increases the susceptibility to develop aggressive prolactinomas in the pituitary gland. Sci Rep 8:7720
Maglakelidze, George; Wynne, Olivia; Sarkar, Dipak K (2017) A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth. J Cell Commun Signal 11:227-232
Chastain, Lucy G; Sarkar, Dipak K (2017) Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology. Alcohol 60:53-66
Rachdaoui, Nadia; Sarkar, Dipak K (2017) Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System. Alcohol Res 38:255-276
Zhang, Changqing; Murugan, Sengottuvelan; Boyadjieva, Nadka et al. (2015) Beta-endorphin cell therapy for cancer prevention. Cancer Prev Res (Phila) 8:56-67
Gangisetty, Omkaram; Wynne, Olivia; Jabbar, Shaima et al. (2015) Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms. PLoS One 10:e0140699
Sarkar, Dipak K (2015) Fetal alcohol exposure increases susceptibility to carcinogenesis and promotes tumor progression in prostate gland. Adv Exp Med Biol 815:389-402
Rachdaoui, Nadia; Sarkar, Dipak K (2014) Transgenerational epigenetics and brain disorders. Int Rev Neurobiol 115:51-73
Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K (2014) Protective effects of hypothalamic beta-endorphin neurons against alcohol-induced liver injuries and liver cancers in rat animal models. Alcohol Clin Exp Res 38:2988-97
Rachdaoui, Nadia; Sarkar, Dipak K (2013) Effects of alcohol on the endocrine system. Endocrinol Metab Clin North Am 42:593-615

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