Date of Award

10-1-1995

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Physiology and Pharmacology

Abstract

Endothelins (ET) are potent vasoactive peptides that are produced in brain and pituitary gland. They exert significant biphasic effects on prolactin release via direct pituitary actions. Endothelins are potent activators of nitric oxide synthase in tissues, such as vasculature and certain neuronal systems.This project tested the hypothesis that the pituitary effects of the endothelins on prolactin release are mediated through the generation of nitric oxide within the anterior pituitary gland via nitric oxide synthase (NOS). Experiments involved the measurement of nitric oxide synthase activity in dispersed anterior pituitary cells by measuring the accumulation of $\sp3$H-L-citrulline from $\sp3$H-L-arginine added to incubations of the cells. Experiments were also conducted to determine whether NO plays a role in ET-induced PRL secretion. Both static and dynamic culture systems were used in these investigations. False substrates for nitric oxide synthesis and substrate removal were methods used in the culture systems to assess nitric oxide's involvement in the endothelins effect on prolactin secretion. Exogenously administered nitric oxide in the culture systems verified the results from the substrate experiments.This study provided the first evidence of the presence of NOS in normal pituitary cells and also demonstrated that NO is not involved in the mechanism by which ET influences PRL secretion. In addition, NO was shown to be a potential modulator of the secretion of other pituitary hormones, such as growth hormone and luteinizing hormone.

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