Secretion by hypothalamic dopaminergic neurons of the aged brain.
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Biomedical subjects
Publications and source records attributed to J C Porter.
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The regional and subcellular distribution of immunoreactive alpha-melanocyte stimulating hormone (alpha-MSHi) in the post mortem adult human brain was investigated. alpha-MSHi was highly concentrated in medial basal hypothalamic tissue (1.02 ng/mg protein). Lower levels of alpha-MSHi were present in the optic chiasm and mammillary bodies, 0.08 and 0.11 ng/mg protein, respectively. The concentrations of alpha-MSHi in cerebellum and frontal cerebral cortex were 1/1,000th that of the medial basal hypothalamus. When medial basal hypothalamic homogenates were subjected to discontinuous or continuous sucrose density gradients, alpha-MSHi was found to be associated primarily with subcellular particles which resembled isolated nerve terminals, i.e., synaptosomes. Low to undetectable amounts of alpha-MSHi were found in the cytosol or the myelin/microsome fraction of the gradients. The results of these studies are consistent with the view that alpha-MSH is a neuronal peptide in the human brain.
The localization of luteinizing hormone releasing hormone (LHRH) in the post mortem adult human brain was investigated. LHRH was highly concentrated in medial basal hypothalamic tissue (1.14 ng/mg protein); lower levels of LHRH were present in tissue from the optic chiasm (0.05 ng/mg protein) and mammillary bodies (0.07 ng/mg protein). The concentrations of LHRH in hypothalamic tissue of men and women were similar. LHRH was undetectable (< 0.001 ng/mg protein) in the frontal cerebral cortex and cerebellum. When homogenates of the medial basal hypothalamus were fractionated on continuous or discontinuous sucrose density gradients, LHRH was found to be associated with subcellular particles. Upon examination by transmission electron microscopy, we found that these subcellular particles resembled isolated neuron terminals, i.e., synaptosomes. Low to undetectable amounts of LHRH were found in the cytosol or the myelin + microsome fraction of the gradients. The results of these studies are supportive of the view that LHRH is highly concentrated in neuron terminals of the adult human brain and may, therefore, be a central neurotransmitter or neuromodulator in the human.
In extracts of anterior pituitary tissue obtained at autopsy of fetal, infant, and adult humans, five molecular forms of immunoreactive ACTH (ACTHi) were detected that had apparent molecular weights of approximately 4044, 30-34, 24-28, 16-18, and 4.5 kilodaltons (K). The relative proportion of each molecular form of ACTHi was similar in tissues that were extracted at the time of autopsy and in tissues that were stored frozen (-20 degrees C) for up to 2 years prior to extraction. We found that 40-44K ACTHi comprised a significantly greater proportion of total ACTHi in fetuses (12.3+/-3.5%) than in adults (3.8+/-0.8%); intermediate amounts of this form of ACTHi (8.0+/-4.1%) were found in tissues obtained from infants. On the other hand, the proportion of 4.5 K ACTHi in fetal pituitaries (67 %) was less than that in those of adults (84 %). The ratio of 40-44/30-34K ACTHi was significantly greater (P<0.001) in fetuses (1.46+/-0.12) and infants (1.31+/-0.07) than in adults (0.52+/-0.07). The ontogenetic differences in molecular forms of pituitary ACTHi are thought to reflect alterations in the processing of proopiomelanocortin as a function of human development.