scholarly journals MicroRNA-9 regulates fetal alcohol-induced changes in D2 receptor to promote prolactin production

2017 ◽  
Vol 235 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Omkaram Gangisetty ◽  
Shaima Jabbar ◽  
Olivia Wynne ◽  
Dipak K Sarkar

Fetal alcohol exposure (FAE) is known to increase prolactin (PRL) secretion from the pituitary lactotropes. In this study, we determined whether microRNAs (miRs) are involved in FAE-induced alteration in PRL release. We employed a rat animal model of FAE involving feeding pregnant Fisher 344 rats with a liquid diet containing 6.7% alcohol between gestational days 7–21 (AF). Both cyclic and estradiol-implanted FAE females showed increased levels of plasma PRL and pituitary Prl mRNA but reduced levels of pituitary dopamine D2 receptor (D2r) and its short spliced form (D2s). FAE increased the expression levels of miR-9 and miR-326 and did not produce any significant changes in miR-153 or miR-200a levels in the pituitary. Effects of FAE on miR-9 and miR-326 were associated with reduced levels of D2r and D2s, increased levels of Prl in the pituitary, and in plasma. These effects of FAE on D2r, D2s and Prl were enhanced following estradiol treatment. In PRL-producing MMQ cells, ethanol increased miR-9 but not miR-326, reduced levels of D2r and D2s and increased levels of Prl. Treatment of MMQ cells with an anti-miR-9 oligo reduced ethanol effects on miR-9, D2r, D2s and Prl. miR-9 mimic oligos reduced the luciferase activity of reporter vector containing D2r 3′UTR, but failed to reduce the mutant luciferase activity. These data suggest that FAE programs the pituitary to produce increased amounts of miR-9 expression that represses the D2r gene and its spliced variant D2s by targeting its 3′UTR leading to an increase in PRL production and secretion.

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2578-2588 ◽  
Author(s):  
Maria A. Agapito ◽  
Changqing Zhang ◽  
Sengottuvelan Murugan ◽  
Dipak K. Sarkar

2018 ◽  
Vol 80 ◽  
pp. 142
Author(s):  
Kaithlyn Delano ◽  
Gideon Koren ◽  
Martin Zack ◽  
Bhushan Kapur ◽  
Joey Gareri ◽  
...  

2010 ◽  
Vol 34 (11) ◽  
pp. 1879-1887 ◽  
Author(s):  
Tiffany A. Polanco ◽  
Catina Crismale-Gann ◽  
Kenneth R. Reuhl ◽  
Dipak K. Sarkar ◽  
Wendie S. Cohick

Author(s):  
Marie R Nakhoul ◽  
Karl E Seif ◽  
Natasha Haddad ◽  
Georges E Haddad

2013 ◽  
Vol 6 (4) ◽  
pp. 977-992 ◽  
Author(s):  
B. I. Laufer ◽  
K. Mantha ◽  
M. L. Kleiber ◽  
E. J. Diehl ◽  
S. M. F. Addison ◽  
...  

2007 ◽  
Vol 102 (3) ◽  
pp. 972-977 ◽  
Author(s):  
Dennis E. Mayock ◽  
Dana Ness ◽  
Robin L. Mondares ◽  
Christine A. Gleason

Alcohol is detrimental to the developing brain and remains the leading cause of mental retardation in developed countries. The mechanism of alcohol brain damage remains elusive. Studies of neurological problems in adults have focused on alcohol's cerebrovascular effects, because alcoholism is a major risk factor for stroke and cerebrovascular injuries. However, few studies have examined similar cerebrovascular effects of fetal alcohol exposure. We examined the effect of chronic binge alcohol exposure during the second trimester on fetal cerebrovascular and metabolic responses to hypoxia in near-term sheep and tested the hypothesis that fetal alcohol exposure would attenuate cerebrovascular dilation to hypoxia. Pregnant ewes were infused with alcohol (1.5 g/kg) or saline intravenously at 60–90 days of gestation (full term = 150 days). At 125 days of gestation, we measured fetal cerebral blood flow (CBF) and oxygen metabolism at baseline and during hypoxia. Maternal blood alcohol averaged 214 ± 5.9 mg/dl immediately after the 1.5-h infusion, with similar values throughout the month of infusion. Hypoxia resulted in a robust increase in CBF in saline-infused fetuses. However, the CBF response to hypoxia in fetuses chronically exposed to alcohol was significantly attenuated. Cerebral oxygen delivery decreased in both groups of fetuses during hypoxia but to a greater degree in the alcohol-exposed fetuses. Prenatal alcohol exposure during the second trimester attenuates cerebrovascular responses to hypoxia in the third trimester. Altered cerebrovascular reactivity might be one mechanism for alcohol-related brain damage and might set the stage for further brain injury if a hypoxic insult occurs.


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