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Biomedical subjects

S C Rappaport

Publications and source records attributed to S C Rappaport.

At least 19 recordsLinked to original sources

Direct radioimmunoassay (RIA) of salivary testosterone: correlation with free and total serum testosterone.

Simple and sensitive direct RIA for determination of salivary testosterone was developed by using RSL NOSOLVEX TM (125 1) kit produced by Radioassay System Laboratories (Carson, California). In addition, a relationship between salivary and serum free and total testosterone concentrations was studied in randomly selected 45 healthy subjects, 5 females on oral contraceptive pills and 28 hypertensive patients on various treatment regimens. The lowest weight of testosterone detectable by our modified method was equivalent to 1 pg/ml of saliva, taking into account analytical variability. Intra- and interassay coefficients of variation were 5.09 +/- 2.7% and 8.2 +/- 5.9% respectively. Statistically significant correlations were found between salivary and serum free testosterone (r = 0.97) and salivary and serum total testosterone concentrations (r = 0.70-0.87). The exception to this was a group of hypertensive females in which no correlation (r = 0.14) between salivary and total serum testosterone was found. It is also of interest that, while salivary testosterone was significantly increased in subjects taking oral contraceptives and most of the hypertensive patients the total serum testosterone concentration was in normal range. Our findings suggest that determination of salivary testosterone is a reliable method to detect changes in the concentration of available biologically active hormone in the circulation.

Adult↗

Phenytoin effect on the proliferation of rat oral epithelium is mediated by a hormonal mechanism.

Systemic pretreatment of male rats with phenytoin (PHT) (30 mg/100 g body weight) significantly (P less than 0.001) increased mitotic frequency, shortened mitotic duration and renewal time in the basal cells of the oral epithelium. This effect of PHT was abolished by simultaneous s.c. injection of cyproterone acetate (CyA) (50 micrograms/100 g body weight) or by castration. CyA treatment of intact rats or castration further decreased mitotic frequency, prolonged mitotic duration and turnover time in the oral epithelium. The effect of castration was reversed by the simultaneous s.c. injection of testosterone propionate (Tp) (50 micrograms/100 g body weight). These results suggest that PHT effect on epithelial proliferation is mediated by a hormonal mechanism.

Animals↗

Specific estrogen receptors in human gingiva.

The cytoplasm of normal human male and female gingiva contains a receptor capable of specifically binding 17 beta-estradiol and moxestrol (R-2858) with high affinity (Kd = approximately 3.4 X 10(-10) M) and low capacity (4.5 fmol/mg protein). The binding is sensitive to heat (destroyed by warming to 37 C for 60 min), proteolytic enzymes (pronase, trypsin, and chymotrypsin), and exhibits a pattern of competition similar to that obtained with estrogen receptors from other target tissues. Nuclear uptake of [3H]estradiol was demonstrated by using a dry autoradiographic technique. Specific nuclear localization of [3H]estradiol was found predominantly in basal and spinous layers of gingival epithelium, stromal connective tissue cells (fibroblasts), and endothelial cells and pericytes of small blood vessels in the lamina propria. There was no difference between the Kd values in normal and diseased tissue or between the Kd values or number of binding sites and the age or sex of the patient. However, there was a difference between the amount of estrogen binding sites per mg protein in normal tissue compared to gingiva with dilantin hyperplasia. These results provide the first direct evidence that human gingiva may function as a target organ for estrogens.

Adolescent↗

Effect of ethanol intake on cellular regulation of testosterone-5 alpha-reductase in rat oral tissues.

The effect of ethanol on testosterone-5 alpha-A-ring reductase activity was studied in the whole homogenate and/or subcellular fractions (microsomes and cytosol) of buccal mucosa, gingiva, liver and prostate from intact ethanol-fed (36% of dietary calories were given as ethanol for up to 360 days) and pair-fed control rats. An increased enzyme activity was found in the hepatic, prostatic and gingival homogenates from ethanol-fed rats. No difference in the enzyme activity was seen in the homogenates of buccal mucosa. However, when the buccal mucosal microsomal fraction was used a significant (P less than .005) increase in the enzyme activity was found in the ethanol-fed rats. It was determined that the lack of an increase in 5 alpha-reductase activity in the buccal mucosal homogenates from ethanol-fed rats was due to the presence of a cytosolic inhibitor of this enzyme. Enzyme kinetics showed a decrease in the velocity in correlation with the increasing concentration of cytosolic inhibitor (Vmax control = 1.9 and Vmax ethanol = 1.7, 1.45 and 1.0 nmol, respectively). The apparent Km (0) and Kp (1--3) values were similar for all combinations (4.5 x 10(-5) M). In addition, a similar Ki constant (2.2 mg of cytosolic protein) was found for different testosterone concentrations. These results suggest that the ethanol-induced cytosolic inhibitor in buccal mucosa combines with the enzyme, independent of the substrate and inhibits it by an allosteric mechanism. Studies using dialysis, heating and tryptic digestion suggests that the inhibitor is a protein.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Concentration of circulating hormones and metabolism of androgens by human gingiva.

The present study evaluates the relationship between periodontal status, concentration of circulating hormones and metabolism of androgens by human male and female gingiva in vitro. In both male and female patients with healthy gingiva the plasma concentration of gonadotropins (LH and FSH) and steroid hormones (testosterone, androstenedione, estradiol-17 beta, progesterone and cortisol) were in a normal range. However, an alteration in the plasma concentration of progesterone was found in both male and female patients with periodontal pathosis. Both androgens (testosterone and androstenedione) were readily metabolized by human gingiva tissue in vitro. The major pathway of the metabolism of testosterone was via the formation of 17 beta-hydroxy-5 alpha-A-ring reduced androgens (5 alpha-dihydrotestosterone and 3 alpha-, 3 beta-androstanediol). In contrast, androstenedione was metabolized mainly to 17-keto-5 alpha-A-ring reduced (5 alpha-androstanedione, androsterone and epiandrosterone) and 17 beta-oxidoreduced (testosterone) compounds. In addition both substrates were metabolized to 5 beta-A-ring reduced androgens (5 beta-dihydrotestosterone, 5 beta-androstanediol and 5 beta-androstanedione). A significant feature of the metabolism of testosterone and androstenedione by inflamed gingiva was an increase of 5 alpha-A-ring reductase activity (mainly the formation of 5 alpha-dihydrotestosterone and 5 alpha-androstanedione) and 17 beta-oxidoreductase activity (mainly the formation of testosterone from androstenedione). The increase in 5 alpha-reductase activity also showed a significant correlation with the plasma progesterone concentration.

Adolescent↗

Effect of progestins on androgen delta4-3-ketosteroid-5alpha-A-ring reductase system in rat oral mucosa.

Rat oral mucosa microsomal delta4-3-ketosteroid-5alpha-A-ring reductase enzyme system, reducing testosterone and 4-androstenedione, was found to be inducible by systemic administration of medroxyprogesterone acetate (MPA). MPA, when used in a mixture with testosterone and/or 4-androstenedione in vitro, acted as a competitive inhibitor of the reduction of these substrates.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗