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Role of beta-endorphin in control of stress and cancer progression in fetal alcohol exposed rats
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Zhang, Changqing. Role of beta-endorphin in control of stress and cancer progression in fetal alcohol exposed rats. Retrieved from https://doi.org/doi:10.7282/T3XS5SG3

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TitleRole of beta-endorphin in control of stress and cancer progression in fetal alcohol exposed rats
NameZhang, Changqing (author); Sarkar, Dipak K (chair); Cohick, Wendie S (internal member); Bello, Nicholas T (internal member); Thomas, Paul E (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2013
Other Date2013-10 (degree)
SubjectAnimal Sciences, Endorphins, Rats--Effect of stress on, Alcohol--Physiological effect, Cancer--Etiology, Cancer in animals
Extentxii, 130 p. : ill.
DescriptionFetal alcohol exposure causes a series of defects in the animals, including hyper-reactivity to stress, impaired immune function, and increased susceptibility to mammary cancer. Production of β-endorphin (β-EP), the neuronal peptide that is known to inhibit the stress axis, is also reduced in the hypothalamus of fetal alcohol exposed animals. Therefore, we hypothesized that the loss of β-EP neurons in the hypothalamus may be the leading cause of the hyper-reactivity to stress, which then compromises the immune system and leads to increased incidence and progression of mammary cancer. Furthermore, we proposed that enhancement of β-EP neuronal function will have therapeutic effects on treating neoplastic diseases. To test this possibility, we developed two methods that can be used to increase the β-EP neuronal numbers in the hypothalamus: 1) transplantation of in vitro differentiated β-EP neurons into the paraventricular nucleus of the hypothalamus; 2) injection of nanosphere-carried cAMP activating reagents into the third ventricle. Both of these methods were shown to significantly increase the β-EP peptide level in the hypothalamus and significantly decrease the activity of stress axis. By using these methods, we could increase the activities of innate immune cells such as NK cells and macrophages, increase the levels of anti-inflammatory cytokines, and inhibit the growth of carcinogen-induced mammary cancer as well as the metastasis of a mammary carcinoma cell line. These beneficial effects on the control of stress activity, immune function and cancer development caused by increased β-EP production in the hypothalamus could be reversed by treating the animals with naloxone (opioid receptor antagonist), metaproterenol (β-adrenergic receptor agonist), and methyllycaconitine (α7 nicotine acetylcholine receptor antagonist). After β-EP neuronal transplantation, nude rats that lack T-cell-mediated adaptive immune reactivity also showed a significant increase in the ability to resist mammary cancer cell metastasis. These data indicate that the effect of increased hypothalamic β-EP production on mammary cancer growth works through activation of the opioid receptor, inhibition of the sympathetic nervous system, activation of the parasympathetic nervous system, and activation of the innate immune function. In conclusion, measures that activate β-EP neurons in the hypothalamus could inhibit activity of the stress axis, increase innate immune function and inhibit mammary cancer growth and metastasis in both normal and fetal alcohol exposed animals. β-EP neuronal loss caused by fetal alcohol exposure may be an important cause of the hyper-reactive stress axis, decreased immune activity and susceptibility to cancer in the fetal alcohol exposed animals.
NotePh.D.
NoteIncludes bibliographical references
NoteIncludes vita
Noteby Changqing Zhang
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3XS5SG3
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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