No abstract

Androgen deprivation subsequent to castration of an adult male rat results in the regression of sexual accessory tissues. Regression of these tissues involves the massive death of androgen-dependent cells. Using the rat ventral prostate gland as a model to study androgen-programed cell death, we have characterized a series of molecular events that accompany its regression. This analysis has shown that there was a sequential induction of specific gene transcripts in the ventral prostate gland following castration. The first event in this cascade was an abrupt induction of transcripts encoding c-fos. Since c-fos expression has been linked to perturbations in intracellular Ca2+ levels, we investigated whether membrane-mediated Ca2+ flux might be an early physiological step involved in the death of prostatic cells. To test this, rats were treated simultaneously upon castration with either verapamil or nifedipine, two different calcium channel antagonist drugs. Compared to the ventral prostate glands of untreated castrated rats, the glands of the calcium channel antagonist-treated rats showed a significant delay in all parameters associated with regression (loss of wet weight and DNA content and delay in histological changes associated with prostatic regression). The seminal vesicle glands of treated rats also showed signs of delayed regression. Furthermore, calcium channel antagonists suppressed the induction of transcripts encoding both c-fos and testosterone-repressed prostate message-2 (TRPM-2), a gene expressed exclusively by dying cells, during the first 62 hr following castration. These findings further support a role for calcium ion influx in the pathway leading to hormonally programed prostate cell death, and suggest the intriguing possibility that modulation of this activity can alter the process by which cells die.

The temporal expression of genes corresponding to eighteen cDNA clones isolated from testis mRNA was analyzed. Two sets of RNA samples were surveyed by means of Northern blot analysis; one set contained poly[A+] RNA from the seminiferous epithelium of mice at different developmental ages and the other contained total cellular RNA from purified germ cells. The purified germ cells represented several morphological stages of spermatogenesis, from spermatogonia to condensing spermatids (steps 12-16) and residual bodies. In this study, four distinct phases of gene expression were observed during spermatogenesis. The clones that were characterized provide molecular markers for stage-specific transcription during germ cell differentiation.

Steady state fluorescence polarization spectra and time-resolved emission decay kinetics have been measured in vitro from malignant and normal rat kidney tissue. The degrees of polarization and emission lifetimes from the cancerous and normal systems are different. The spectroscopic differences are attributed to environmental transformations local to the native flavin and porphyrin fluorophors' binding sites.

The present study investigated the effect of a surgically induced varicocele on the dynamics of testicular blood flow. The surface vasculature of the normal and the varicocele-affected testis was examined utilizing intravital epi-illumination microscopy. Application of this technique to the study of the varicocele is new. Blood flow characteristics in surface veins were studied as the surface temperature of the testis was varied. Periodic, reproducible stoppages in blood flow, determined by direct observation of the red blood cells, were seen in seven of eight sham animals at the lower temperatures. These stoppages were abolished and blood flow increased at higher temperatures; stoppages reappeared at lower temperatures. The periodic stoppages were present in only one of eight rats with a proven varicocele (P less than 0.025) at any temperature studied. This loss of blood flow regulation may be the result of a loss of testicular arteriolar tone and may explain the increase in testicular blood flow and temperature elevation observed in association with a varicocele. These findings may provide new insights into the pathophysiology of the varicocele and highlight the need to study the microvascular sequelae of this vascular abnormality.