Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs.

There was no significant relationship between the survival rate in dogs with nonseptic SIRS or sepsis and the initial serum CRP concentrations. There was a correlation between decreasing CRP concentrations and recovery from disease. However, the changes in CRP concentrations over a 3-day period correctly predicted survival in 94% of dogs and death in 30% of the dogs (false positive rate 22%).

Background: In mammals the composition of milk changes during early lactation showing a rapid decline in fat-soluble vitamins and a continuous increase in total lipids. Changes in the concentrations of carotenoids, vitamin A, α-tocopherol and total lipids in human milk (colostrum, transitory and mature milk) were studied to understand this not well characterised phenomenon. Methods: Colostrum, transitory and mature milk was collected from 21 women and analysed for carotenoids, vitamin A and α-tocopherol by HPLC. Results: Total lipids increased from the lowest levels in colostrum (1.5 ± 1.6 mg/ml) to the highest in transitory milk (3.6 ± 2.5 mg/ml, p < 0.01). Contrary to this, levels of total carotenoids (236.7 ± 121.9 ng/ml), vitamin A (1.02 ± 0.56 µg/ml) and α-tocopherol (11.8 ± 6.3 µg/ml) were highest in colostrum and declined significantly during the first weeks of lactation (63.2 ± 23.3 ng/ml, 0.33 ± 0.14 µg/ml, 2.7 ± 1.1 µg/ml, respectively; p < 0.001). Conclusions: The magnitude of decrease was not the same for all carotenoids and was dependent on the polarity of the carotenoid with the smallest decrease in the polar carotenoids. This might be due to differences in the distribution of carotenoids among plasma lipoproteins and might point to possible selective mechanisms being involved in the transfer of these components in early human milk.

In mammals the composition of milk changes during early lactation, with a rapid decline of fat-soluble vitamins and a continuous increase in total lipids. The mechanisms underlying this phenomenon are not well understood, but might involve selective mechanisms related to mammary uptake or secretion into the milk. Since carotenoids are specifically distributed among the lipoprotein fractions in plasma, the simultaneous determination of carotenoids in plasma, lipoprotein fractions and milk might offer an opportunity to gain insight into this phenomenon. In 21 healthy mothers carotenoids in plasma and lipoprotein fractions were investigated at day 2 and 19 and milk on day 4 and 19 after delivery. Plasma levels of alpha-tocopherol and cholesterol as well as lutein, zeaxanthin and cryptoxanthin were significantly lower later in lactation (day 19) than shortly after birth (P < 0.01). The stage of lactation had no effect on the distribution of carotenoids and alpha-tocopherol among the plasma lipoprotein fractions. In milk, triacylglycerol increased (P < 0.01). In contrast, levels of carotenoids, alpha-tocopherol and vitamin A were highest in colostrum and declined (P < 0.01). Because the magnitude of decrease was not the same in all carotenoids, the carotenoid pattern changed substantially. In colostrum the carotenoid pattern resembled those of plasma and the low-density lipoprotein fraction. In mature milk it was similar to the pattern found in the high density lipoprotein fraction. Based on these observations a selective mechanism might be responsible for the transfer of these components in milk involving different lipoprotein fractions at specific times of lactation.

The noncovalent binding of selected phenolic compounds (chlorogenic-, ferulic-, gallic acid, quercetin, rutin, and isoquercetin) to proteins (HSA, BSA, soy glycinin, and lysozyme) was studied by an indirect method applying the quenching of intrinsic tryptophan fluorescence. From the data obtained, the binding constants were calculated by nonlinear regression (one site binding; y = Bx/k + x). It has been reported that tannins inhibit human salivary amylase and that these complexes may reduce the development of cariogenic plaques. Further, amylase contains two tryptophan residues in its active site. Therefore, in a second part of the study involving 31 human subjects, evidence was sought for noncovalent interactions between the phenols of green tea and saliva proteins as measured by the fluorescence intensity. Amylase activity was determined before and after the addition of green tea to saliva of 31 subjects. Forty percent of the subjects showed an increase in amylase activity contrary to studies reporting only a decrease in activity. The interactions of tannin with amylase result in a decrease of its activity. It still remains to be elucidated why amylase does not react uniformly under conditions of applying green tea to saliva. Further, in terms of using phenols as caries inhibitors this finding should be of importance.