PHYSIOLOGICAL STUDIES OF BETA-ENDORPHIN IN BLOOD PLASMA

LAWRENCE STEVEN LESHIN, Purdue University

Abstract

Evidence exists for the involvement of the opioid peptide (beta)-endorphin ((beta)-EP) in neuroendocrine and autonomic nervous system regulation. A radioimmunoassay for the quantification of (beta)-EP in plasma, CSF and tissues was developed and validated to facilitate studies of the neuro-endocrine effects pertaining to endogenous (beta)-EP. While (beta)-EP could be validly assayed in unextracted plasma, chromatographic procedures indicated that (beta)-LPH comprised approximately one-half of the detectable ovine plasma (beta)-EP immunoreactivity. Possible endocrinological effects of plasma (beta)-EP were studied in ovariectomized ewes during acute septicemia. The bacterial stimulus produced dramatic increases in plasma (beta)-EP simultaneously with the occurrence of tachycardia and increased packed cell volume. Following these initial changes, body temperature increased, respiration decreased, while plasma concentrations of LH decreased and PRL and GH increased. However, only a few variables were significantly correlated with the magnitude of the (beta)-EP increase. Furthermore, continuous naloxone infusion beginning before bacteria administration failed to alter the observed responses, with the exception of GH. The increases of plasma GH were delayed, but not attenuated, by naloxone infusion. These results suggest that plasma (beta)-EP probably does not modulate these septicemic responses. CNS opiates may account for the naloxone induced GH effect. Experiments were performed to test the hypothesis of retrograde delivery of plasma (beta)-EP from the pituitary directly to the brain. Blood was sampled simultaneously at 20-sec intervals from the sagittal sinus, jugular vein, and carotid artery. (beta)-EP release was provoked and the diencephalic plasma effluent was statistically examined for (beta)-EP concentrations greater than those in concurrent arterial samples. Bacteria-induced septicemia was the most effective stimulus to raise plasma (beta)-EP. High doses of naloxone also raised plasma (beta)-EP and tended to increase LH. When the hormone data accounted for the episodic secretion of pituitary hormones and circulating transit time between the sampling locations, no evidence of retrograde delivery of pituitary hormones was found for (beta)-EP, LH, or PRL. Furthermore, plasma concentrations of (beta)-EP were not correlated to CSF concentrations. In summary, the data presented in this thesis do not support an endocrinological role for plasma (beta)-EP.

Degree

Ph.D.

Subject Area

Anatomy & physiology|Animals

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