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A major androgen-dependent urinary protein of male rodents, alpha 2u-globulin, has been shown to influence adenohypophyseal hormone release. In an attempt to elucidate the mechanisms of its action, we have examined several parameters of hypothalamic and pituitary function in adult male rats treated for 2 weeks with two injections daily of 0.75 mg alpha 2u-globulin and sacrificed 16 h after the last injection. This treatment led to an increase in plasma luteinizing hormone levels, a decrease in plasma prolactin levels, an increase in testosterone concentrations in both plasma and testicular tissue, and increases in testicular weights. The norepinephrine turnover in median eminence and anterior hypothalamus was increased in alpha 2u-globulin-injected animals, while the norepinephrine turnover in the remaining medial basal hypothalamus was reduced. alpha 2u-Globulin-treated animals had a significantly decreased dopamine turnover in the anterior hypothalamus, while in the medial basal hypothalamus the dopamine metabolism was increased. These data suggest that alpha 2u-globulin-induced changes in gonadotropin and prolactin secretion are mediated by changes in catecholamine metabolism in several hypothalamic regions. Increased testosterone secretion appears to be due to increased secretion of gonadotropins from the pituitary.

alpha-Globulins prepared from different biological sources (human and bovine sera, mouse ascitic fluid, human ovarian cyst fluid) were separated by ion exchange chromatography on DEAE-cellulose into fractions A, B and C. Whereas fractions A and B had no immunosuppressive activity, fraction C injected into mice shortly before antigen administration, but not after, significantly inhibited the contact sensitivity to oxazolone. Single high doses were preferential over divided doses given on several occasions. In transfer experiments when cells of animals sensitized to oxazolone were injected into recipients treated previously with fraction C, the response was also inhibited. Fraction C, when administered into F1 hybrid mice before injection of parental splenocytes, prevented the development of GVH reaction. The authors point out that the critical concentration of alpha-globulins at the time of antigen administration is necessary to make T-lymphocytes hyporesponsive, and when once triggered by antigen they become refractory to alpha-globulins action.

The present study was undertaken to determine if urinary protein can produce urinary stones and what types of protein have such an effect. Normal human serum was fractionated first with ammonium sulfate and then with DEAE-cellulose. The stone-forming action of each fraction was estimated by calculating their ability to alter the sedimentation rate and zeta-potential of a calcium carbonate suspension. Finally, the proteins in each fraction were identified by cellulose acetate electrophoresis. The most marked aggregating and precipitating effect on a CaCO3 suspension was observed with a mixture of proteins of alpha1-globulin and albumin fractions. However, beta- and gamma-fractions had little aggregating effect on the CaCO3 suspension.

Suppression of the plaque-forming cell response in mice following injection of substances fractionated from pooled normal serum alpha-globulin was investigated. The dose-response relationship for fractions obtained by ion-exchange chromatography show that a single preparation has both enhancing and suppressive activities which are revealed at different doses. Whether this observation reflects the sum of activities of a number of molecular species remains to be determined. The immune responses to both thymus-dependent (heterologous erythrocytes) and thymus-independent (DNP-ficoll) antigens are suppressed while the response to the thymus-independent antigen lipopolysaccharide is enhanced. Thus, the cellular locus for immunosuppression cannot be exclusively on the T cell, and the magnitude of the action of the two populations (T and B cells) remains unclear.