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Biomedical subjects

R Santti

Publications and source records attributed to R Santti.

51 records · Page 3Linked to original sources

Testosterone concentrations in human seminal plasma and saliva and its correlation with non-protein-bound and total testosterone levels in serum.

A sensitive, specific and precise non-chromatographic method for the radioimmunoassay of testosterone in human seminal plasma and saliva from adult and pubertal males is described, and the values compared to total and non-protein-bound testosterone levels in serum. There was a significant correlation between salivary and serum-free levels of testosterone (r = 0.75, P less than 0.001, n = 67) whilst the correlation of serum levels of total testosterone with free as well as with salivary testosterone levels was weaker (r = 0.63 and 0.64, respectively). The salivary and serum levels of free testosterone showed better correlation with the stage of puberty than did the serum levels of total testosterone. Further evidence for a correlation between salivary and serum levels of free testosterone was obtained following oral administration of testosterone undecanoate, as this treatment increased the mean concentration of serum total testosterone after 3 h by 82%, but increased salivary and serum levels of free testosterone by only 30% and 20%, respectively. The coefficient of correlation between serum levels of total testosterone and seminal plasma testosterone was 0.73 (P less than 0.001), whilst the correlation between levels of serum-free testosterone with both salivary and seminal plasma levels of testosterone was statistically non-significant. Our observations on salivary testosterone are in accordance with the diffusion of non-protein-bound steroids into peripheral tissues, and consequently into their secretions. This model, however, does not appear to be applicable to the sex accessory glands.

Adolescent↗

Androgenic control of polysomal poly(A)-containing RNA in the cultured rat ventral prostate.

Testosterone stimulated, at the concentration of 10-7 M and independently of other hormones, the accumulation of polysomal poly(A)-containing RNA (mRNA) in cultured explants of rat ventral prostate and concomitantly also protein synthesis. The hormone-induced accumulation of polysomal mRNA, which reached its maximum at 24 h after testosterone addition, paralleled the preferential labeling of high molecular weight RNA demonstrable with the electrophoretic analysis of the double-isotope labeled RNA after a short pulse (30 min). These findings are consistent with the idea that testosterone activated the synthesis of precursor mRNA leading to an increased amount of polysomal mRNA and eventually an activated protein synthesis. The synthesis and maturation of rRNA appeared to proceed even in the absence of testosterone, which is in contrast to the vivo findings on castrated rats. This partial uncoupling of RNA synthesis from androgenic control may account for the slow and less marked hormonal responses found in protein synthesis and glucose metabolism in cultured explants from normal animals. Because of the lack of uniformity in the suture, routine light microscopic control to assess the viability of cultured explants was found to be a prerequisite for successful biochemical work on prostate culture.

Animals↗

Ultrastructural study of hydrocortisone action in cultured human epidermis.

Adult human skin was maintained in organ culture in a chemically defined medium without serum for up to 10 days. Under these conditions cultured epidermis revealed ultrastructural changes suggesting alterations in keratinization. Half of the newly formed stratum corneum became parakeratotic. The number and size of keratohyalin granules were reduced, and only few keratinosomes were present after the 5th day of culture. The effect of hydrocortisone at final concentrations of 10(-5)-10(-9) mol/l was studied by applying stereological techniques for electron microscopic morphometry on systematically sampled tissues. The volume densities of tissue components and cell organelles were assessed at three different strata of epidermis on the 5th day of culture. Changes of keratinization due to the culture conditions were partly reversed by the hormone, i.e. hydrocortisone increased the volume densities of keratohyalin granules, keratinosomes and tonofilaments. Minute effects due to hormonal action were seen on tissue components or the volume densities of other cellular organelles.

Adult↗

Correlation of early cytodifferentiation of the human fetal prostate and Leydig cells.

The ultrastructural differentiation of the human prostatic epithelium and mesenchyme was studied in early developing glands and correlated with the differentiation of the Leydig cells of the same individuals during the tenth to sixteenth weeks. After initial folding of the basal lamina, the epithelial cells began to migrate into the differentiated, condensed mesenchyme at the end of the 10th week, and in the 11th week some of the prostatic outgrowths acquired a lumen. The acinar and tubular epithelium in the fetal prostate remained stratified, and adult type simple epithelium was not seen during the period between the 10th and 16th weeks. As a sign of incipient secretory activity, a few epithelial cells became polarized, and secretion granules with flocculent or dense content appeared in the Golgi area and in the apical parts of the cells in the 13th week. Occasional direct epithelio-mesenchymal cell contacts were visible in association with the appearance of the secretory activity. Two cell types, not seen in the normal adult prostate, appeared in the epithelium of the primitive glands. Their nature and role in the glandular morphogenesis are not clear. During this time, the ultrastructural differentiation of the Leydig cells continued and their size and number increased. They occupied almost the whole interstitium by the time secretion granules appeared in the prostatic cells. These findings support the current notion that androgens secreted by Leydig cells are the major regulators of prostatic development in man.

Cell Differentiation↗

Glucose content as a parameter of semen quality.

There are minute and varying amounts of glucose in seminal plasma. Findings on vasectomized men suggest that it is derived from accessory sex glands. The glucose content was shown to correlate negatively to the number of spermatozoa and the time period elapsed from ejaculation, indicating that seminal glucose was utilized by spermatozoa even in the presence of a 50-fold concentration of fructose. Large interindividual variations in the glucose utilization as reflected in the 14CO2 production from 14C-glucose by spermatozoa could not be explained by the parameters examined in routine semen analysis. Fructose and glucose maintained equally well the ATP content and motility of spermatozoa at the concentrations found normally in semen. Fructose may thus supplement and substitute for glucose as an energy source, and the addition of glucose into the semen or the measurement of its content would not give any advantage for the analysis of semen samples.

Diabetes Mellitus↗

Early cytodifferentiation of human prostatic urethra and Leydig cells.

The ultrastructure of the urethral epithelium and mesenchyme of the 6- to 9-week-old human embryos was studied in order to reveal early morphological signs of prostatic development. The morphological changes of the urethral wall were correlated with the cytodifferentiation of the Leydig cells of the same embryos. Throughout the study the urethral epithelium had two or more layers of cuboidal cells. The ultrastructure of the cells was primitive and they did not achieve characteristics of the secretory prostatic cell. The surface cells had well developed apical junctions and slender cytoplasmic processes projecting into widened intercellular spaces appeared during the developmental period. The urethral mesenchyme showed the most salient changes. The mesenchymal cells adjacent to the urethral epithelium differentiated in the ninth week inot fibroblast-like cells with an elongated shape and cytoplasmic processes. Granular endoplamic reticulum appeared in the cytoplasm and collagen fibers were seen in the intercellular space. Mesenchymal cell processes contacting the continuous basal lamina under the epithelium were present. No direct epithelio-mesenchymal cellular contacts could be seen. The differentiation of the mesenchyme before the epithelial outgrowths that the mesenchyme has an essential role in the glandular development. Electron microscopic study of the Leydig cells showed that the amount of agranular endoplasmic reticulum increased considerably in the ninth week. This agrees with earlier biochemical findings on the capability of Leydig cells to produce androgens by this time. The temporal relationship between the cytodifferentiation of Leydig cells and the urethral wall is consistent with the idea that in the human, fetal androgens induce prostatic development.

Cell Differentiation↗

Histometric analysis of human skin in organ culture.

A histometric method is used for the study of human skin kept in organ culture in a defined medium for up to 10 days. The method provides quantitative, reproducible data on tissue survival, cell migration, and cellular differentiation (keratinization). With this method, the behavior of epidermal skin tissue can be effectively monitored during organ culture. As quantitative data are obtained, even subtle changes can be accurately demonstrated, and accumulated data may be subjected to statistical analysis. The various applications of this method are pointed out.

Adult↗

Phytoestrogens: potential endocrine disruptors in males.

Exposure to diethylstilbestrol (DES) induces persistent structural and functional alterations in the developing reproductive tract of males. It is possible that xenoestrogens other than DES alter sexual differentiation in males and account for the increasing incidence of developmental disorders of the reproductive tract in men and wild animals. Phytoestrogens (coumestans, isoflavonoids, flavonoids, and lignans) present in numerous edible plants are quantitatively the most important environmental estrogens when their hormonal potency is assessed in vitro. They exert their estrogenic activity by interacting with estrogen receptors (ERs) in vitro. They may also act as antiestrogens by competing for the binding sites of estrogen receptors or the active site of the estrogen biosynthesizing and metabolizing enzymes, such as aromatase and estrogen-specific 17 beta-hydroxysteroid oxidoreductase (type 1). In theory, phytoestrogens and structurally related compounds could harm the reproductive health of males also by acting as antiestrogens. There are very little data on effects of phytoestrogens in males. Estrogenic effects in wildlife have been described but the evidence for the role of phytoestrogens is indirect and seen under conditions of excessive exposure. In doses comparable to the daily intake from soybased feed, isoflavonoids such as genistein were estrogen agonists in the prostate of adult laboratory rodents. When given neonatally, no persistent effects were observed. In contrast, the central nervous system (CNS)-gonadal axis and the male sexual behavior of the rat appear to be sensitive to phytoestrogens during development. The changes were similar but not identical to those seen after neonatal treatment with DES, but higher doses of phytoestrogens were needed.

Animals↗

Constant expression of cyclooxygenase-2 gene in prostate and the lower urinary tract of estrogen-treated male rats.

Expression of cyclooxygenase-2 (E. C. 1.14.99.1) in prostate and the lower urinary tract (LUT) of the neonatally estrogenized male rat has been studied by using a COX-2's PCR fragment of 724 nt spanning 3 introns and a 478nt internal standard for quantitative RT-PCR. The same fragment of 724 nt was used for RNA probe in Northern hybridization. Neonatal estrogenization (10 microg/day of diethylstilbestrol on days 1-5) had no effect on COX-2 expression in prostatic urethra, prostatic lobes, or bladder. Acute estrogen treatment of castrated animals did not induce COX-2 expression, either. In addition the differential expression of basal level of COX-2 in the different lobes of prostate in normal rat was demonstrated. Our results suggest a constant expression of COX-2 gene in prostate and the lower urinary tract of the neonatally estrogenized (neoDES) rats. The present study indicates that the increased expression of COX-2 is probably not essential for the estrogen-driven development of stromal inflammation or hyperplastic and dysplastic alterations in the prostate of neoDES rats.

Animals↗