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Immunoreactive β-Casomorphin-8 in Cerebrospinal Fluid From Pregnant and Lactating Women: Correlation With Plasma Levels^*

Department of Pharmacology (F.N., H.L., L.T.) and Psychiatric Research Center, Ulleråker Hospital (L.H.L.), University of Uppsala Uppsala, Sweden
The Department of Gynecology and Obstetrics, University Hospital (S.L.) Uppsala, Sweden
The Rudolf Buchheim-Institut für Pharmakologie (G.K.) D-6300 Giessen, West Germany

Address all correspondence and requests for reprints to: Dr. L. Terenius, Department of Pharmacology, University of Uppsala, P.O. Box 591, S-75124 Uppsala, Sweden.

We measured plasma and cerebrospinal fluid (CSF) β-casomorphin-8, a product of β-casein hydrolysis which has opioid activity, by RIA in women during late pregnancy and lactation and in nonpregnant nonpuerperal women. Before RIA, the samples were acidified and extracted by reverse phase silica gel chromatography, which removed most of the β-casein. Lactating women had a significantly higher mean plasma β-casomorphin-8 concentration (2.66 nmol/L; n = 8) than women in late pregnancy (0.82 nmol/L; n = 8) and nonpregnant women (0.32 nmol/L; n = 5). The CSF β-casomorphin-8 concentration also was significantly higher in lactating women (mean, 0.35 nmol/L; n = 8) than during late pregnancy (0.22 nmol/L; n = 8) or in nonpregnant women (0.15 nmol/L; n = 5). A positive correlation was found between plasma and CSF β-casomorphin-8 levels in the entire study group. The milk β-casomorphin-8 concentration, measured in five puerperal women, averaged 19.8 nmol/L. Thus, there is a decreasing concentration gradient between milk and plasma and between plasma and CSF.

Chromatographic analysis revealed mol wt heterogeneity of the RIA-active material. In CSF at least three different components were detected, two of mol wt around 900–2,000 and one of approximately 12,000. One of the low mol wt components coeluted in several chromatographic systems with synthetic β-casomorphin-8 (mol wt, 900). Such a component was not found in milk or plasma, in which the major activity was due to larger sized peptides. The major peaks in milk were around 1,500–2,000 and 12,000 mol wt, corresponding to the larger peaks in CSF.

The results suggest that fragments of the milk protein β-casein may cross the breast parenchyma-blood barrier into plasma and subsequently penetrate the blood-brain barrier to reach the central nervous system. Thus, mammary tissue may assume endocrine function during galactopoesis, and β-casein could be considered a prohormone.

^* This work was supported by Harald Jeansson, Greta and Harald Jeanssons Stiftelse, Amundson’s Fund, and the Swedish Medical Research Council (Grant 5095).

Received June 15, 1988.

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