Phorbol ester activation of the protein kinase C pathway inhibits gonadotropin-releasing hormone gene expression.

The effects of the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C (PKC), and the PKC inhibitor staurosporine on GnRH secretion and mRNA levels were studied in GT1-7 hypothalamic neuronal cells. Dose-response and time-course studies revealed that TPA (10(-8) M) acutely increased GnRH secretion 3-fold at 3-6 h, which then declined to baseline at 24 h, while it progressively decreased GnRH mRNA levels by 50% and 70% at 6 and 24 h, respectively. To ensure that these effects were due to activation and not down-regulation of PKC, cells were treated for 30 min with TPA (10(-8) M). This brief exposure to TPA also resulted in a decrease (60%) in GnRH mRNA levels at 6 h, with a 1.5- to 2-fold increase in GnRH secretion compared to control values, suggesting that activation of PKC decreases the pretranslational expression of GnRH while increasing GnRH secretion. Additional studies measured PKC activity and documented a shift from a cytosolic to a membrane fraction after incubation with TPA, again supporting PKC activation. Exposure of GT1-7 cells to staurosporine (10(-8) M), a PKC inhibitor, resulted in no change in the level of GnRH mRNA or secretion at 6 h. However, incubation with both TPA and staurosporine prevented the decrease in GnRH mRNA levels and partially blocked the increase in GnRH secretion induced by TPA. We conclude that TPA, by activating the PKC pathway, acutely increases GnRH secretion, but dramatically decreases GnRH gene expression. The exact mechanism of these divergent effects on the synthesis and secretion of GnRH remain to be elucidated.

Morphometric aspects of the jugular foramen in dry skullsof adult individuals in Southern Brazil

The jugular foramen (JF) lies between the occipital bone and the petrosal portion of the temporal bone, andit allows for the passage of important nervous and vascular elements, such as the glossopharyngeal vagusand accessory nerves, and the internal jugular vein. Glomic tumors, schwannomas, metastatic lesions andinfiltrating inflammatory processes are associated with this foramen, which can account for injuries of relatedstructures. Variatons of the JF were already reported regarding shape, size and laterality in one only skull,besides differences related to sex, race and laterality domain, which makes the study of these parameters in thepopulation of southern Brazil significant. Objective: this paper wants to conduct the morphometric analysisof the JF of 111 dry skulls belonging to males and females. Results: the latero-medial the anteroposteriormeasurements showed significant differences when genera were compared and side was compared, respectively.Of the total amount of the investigated skulls, 0.9% showed a complete septum on both sides; 0.9% showedincomplete septum, and 83.8% lacked the septum. The presence of a domed bony roof was noticed in 68.5%of skulls on both sides. Conclusion: the obtained results presented variations regarding some parameterswhen compared to previous studies, thus making it evident the significance of race in the morphometricmeasurements and characteristics of the JF, besides the relevance of studying the kind of impairment whichcan jeopardize important functions, as the cardiac innervation of the vagus nerve.