Localization of p24 putative cargo receptors in the early secretory pathway depends on the biosynthetic activity of the cell.

Members of the p24 family of putative cargo receptors (subdivided into p24-alpha, -beta, -gamma and -delta) are localized in the intermediate-and cis-Golgi compartments of the early secretory pathway, and are thought to play an important role in protein transport. In the present study, we wondered what effect increased biosynthetic cell activity with resulting high levels of protein transport would have on the subcellular localization of p24. We examined p24 localization in Xenopus intermediate pituitary melanotrope cells, which in black- and white-adapted animals are biosynthetically highly active and virtually inactive respectively. In addition, p24 localization was studied in Xenopus anterior pituitary cells whose activity is not changed during background adaptation. Using organelle fractionation, we found that in the inactive melanotropes and moderately active anterior pituitary cells of white-adapted animals, the p24-alpha, -beta, -gamma and -delta proteins are all located in the Golgi compartment. In the highly active melanotropes, but not in the anterior cells of black-adapted animals, the steady-state distribution of all four p24 members changed towards the intermediate compartment and subdomains of the endoplasmic reticulum (ER), most probably the ER exit sites. In the active melanotropes, the major cargo protein pro-opiomelanocortin was mostly localized to ER subdomains and partially co-localized with the p24 proteins. Furthermore, in the active cells, in vitro blocking of protein biosynthesis by cycloheximide or dispersion of the Golgi complex by brefeldin A led to a redistribution of the p24 proteins, indicating their involvement in ER-to-Golgi protein transport and extensive cycling in the early secretory pathway. We conclude that the subcellular localization of p24 proteins is dynamic and depends on the biosynthetic activity of the cell.

A comparative investigation of contraceptive reliability, cycle control and tolerance of two monophasic oral contraceptives containing either drospirenone or desogestrel.

OBJECTIVE: To assess the contraceptive reliability, cycle control and tolerance of a new monophasic oral contraceptive (Yasmin) containing 30 microg ethinylestradiol and 3 mg drospirenone and compare it with a preparation containing an equal dose of ethinylestradiol combined with 150 microg desogestrel (Marvelon). METHODS: A multicenter, open-label, randomized study was carried out in 26 European centers. Contraceptive efficacy, cycle control and tolerance (including body weight, blood pressure and heart rate) were assessed over 26 cycles, plus a 3-month follow-up period. RESULTS: Of 900 women who were randomized, 887 started treatment and 627 completed the 26 cycles plus follow-up (310 in the ethinylestradiol/drospirenone group and 317 in the ethinylestradiol/desogestrel group). Both study preparations were found to be effective with regard to contraceptive reliability and cycle control was good. There were six pregnancies (three in each group), but none were considered to have been the result of method failures. The subjective and objective tolerances were good in both groups. A statistically significant difference was found in body weight changes between the two groups. While there was an increase in mean body weight in the ethinylestradiol/desogestrel group from cycle 5 onward, the mean body weight per cycle in the ethinylestradiol/drospirenone group was slightly below the baseline value throughout the study. The incidence ofpremenstrual symptoms was higher in the ethinylestradiol/drospirenone group than in the ethinylestradiol/desogestrel group during the 6 months prior to the study, but lower during treatment. The rates ofdysmenorrhea were identical under both treatments but the symptoms were more often mild and less often severe in the ethinylestradiol/drospirenone group. CONCLUSION: The combination of 30 microg ethinylestradiol combined with 3 mg drospirenone provides effective oral contraception and good cycle control, and is well tolerated. Ethinylestradiol/drospirenone had a more favorable effect on body weight than ethinylestradiol/desogestrel, with the mean body weight remaining lower than baseline for the majority of the women.

Differential induction of two p24delta putative cargo receptors upon activation of a prohormone-producing cell.

The p24 family consists of type I transmembrane proteins that are present abundantly in transport vesicles, may play a role in endoplasmic reticulum-to-Golgi cargo transport, and have been classified into subfamilies named p24alpha, -beta, -gamma, and -delta. We previously identified a member of the p24delta subfamily that is coordinately expressed with the prohormone proopiomelanocortin (POMC) in the melanotrope cells of the intermediate pituitary during black background adaptation of the amphibian Xenopus laevis ( approximately 30-fold increase in POMC mRNA). In this study, we report on the characterization of this p24delta member (Xp24delta(2)) and on the identification and characterization of a second member (Xp24delta(1)) that is also expressed in the melanotrope cells and that has 66% amino acid sequence identity to Xp24delta(2). The two p24delta members are ubiquitously expressed, but Xp24delta(2) is neuroendocrine enriched. During black background adaptation, the amount of the Xp24delta(2) protein in the intermediate pituitary was increased approximately 25 times, whereas Xp24delta(1) protein expression was increased only 2.5 times. Furthermore, the level of Xp24delta(2) mRNA was approximately 5-fold higher in the melanotrope cells of black-adapted animals than in those of white-adapted animals, whereas Xp24delta(1) mRNA expression was not induced. Therefore, the expression of Xp24delta(2) specifically correlates with the expression of POMC. Together, our findings suggest that p24delta proteins have a role in selective protein transport in the secretory pathway.

Quantitative morphology of the placenta. III. The growth of the placenta and its relationship to birth weight.

The relationship of placental components to birth weight was investigated by stereology. 37 placentas from nonpathological pregnancies delivered after a period of 224-303 days of amenorrhea were examined. The umbilical cord was clamped immediately after birth. The ratios of the volume, the surface, the length of the villous vessels and the surface of the villi with birth weight showed a decrease after 277 days of amenorrhea. In contrast to this decrease, the ratio of the volume of the trophoblast with birth weight seems to increase. No difference could be found for the ratios of the placental volume (placental index), the volume of the villous tissue, the volume of the intervillous space and the volume of the nonfunctional tissue with birth weight. These ratios reveal a quantitative morphological base for the clinical experience that postmature fetuses are at a higher risk through deterioration of the placenta.

Quantitative morphology of the placenta. II. The growth of the placenta and the problem of postmaturity.

The morphological changes in the placenta concomitant with the transition from maturity to postmaturity were investigated by stereology under early clamping of the umbilical cord. 37 placentas from nonpathological pregnancies delivered after a period of 224-303 days of amenorrhea were examined. It appeared that after 267-288 days of amenorrhea, 8 out of 9 placental components showed no further growth and even showed regression. Only the volume of the trophoblast continued to grow in postmaturity. It is suggested that during postmaturity the villous capacity to produce steroids is continuing at a normal rate (as judged by the increase of the volume of the trophoblast), whereas the capability to transfer is deteriorating (as testified by the decreasing surface of the trophoblast).