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Biomedical subjects

L L Ewing

Publications and source records attributed to L L Ewing.

At least 91 records · Page 5Linked to original sources

Steroid secretion by in vitro perfused testes: testosterone biosynthetic pathways.

Alternative metabolic pathways for the biosynthesis of testosterone from pregnenolone exist in mammalian testes. The following experiments were designed to identify the preferred testosterone biosynthetic pathway in rat and rabbit testes. The experimental protocol included the infusion of steroidogenic reaction inhibitors and testosterone biosynthetic intermediates into testes perfused in vitro. Under these conditions, the testicular steroid secretions were a measure of specific reaction activities. Infusion of medrogestone (6,17-dimethyl-4,6-pregnadiene-3,20-dione, Ayerst), an inhibitor of delta5-4isomerization, permitted the reactions converting pregnenolone to androstenediol to be studied separately from those converting progesterone to testosterone. For example, the activity of the pregnenolone vector 17alpha-hydroxypregnenolone reaction was measured as the total of the 17alpha-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol secreted by medrogestone-inhibited testes. The reactions convering delta5-3beta-hydroxysteroids to delta4-3-ketosteroids were studied in testes infused with SU-10603 (7-chloro-3,4-dihydro-2-[3-pyridyl]-1(2H)-naphthalenone. Ciba-Geigy), an inhibitor of 17alpha-hydroxylation and C-17, C-20 cleavage reactions. The results indicated that preferred testosterone biosynthetic pathways are present and different in rat and rabbit testes.

Animals↗

Comparison of spontaneous and experimentally induced canine prostatic hyperplasia.

Spontaneous prostatic hyperplasia in the beagle appears to progress with age from a glandular to a cystic histological appearance. Prostatic hyperplasia can be induced in young beagles with intact testes by treatment for 4 mo with either dihydrotestosterone or 5 alpha-androstane-3 alpha, 17 beta-diol, alone, or with either of these steroids in combination with 17 beta-estradiol. In contrast, the induction of prostatic hyperplasia in young castrated beagles, in which the gland had been allowed to involute for 1 mo, requires the administration of both 17 beta-estradiol and either 5 alpha-androstane-3 alpha, 17 beta-diol or dihydrotestosterone. Testosterone and 17 beta-estradiol, either singly or in combination, did not produce the hyperplastic condition in intact or castrated beagles. The experimentally induced prostatic hyperplasia is identical in pathology to the glandular hyperplasia that occurs naturally in the aging dog with intact testes. However, cystic hyperplasia was not produced by any of the treatments tested in young animals.

Androstane-3,17-diol↗

Testosterone secretion by rat, rabbit, guinea pig, dog, and hamster testes perfused in vitro: correlation with Leydig cell mass.

Testes from guinea pigs, rabbits, dogs, rats, and hamsters perfused in vitro with maximally stimulating concentrations of ovine LH released 9.76 +/- 2.05, 12.80 +/- 3.15, 28.94 +/- 3.01, 3.18 +/- 0.41, and 0.70 +/- 0.12 microgram testosterone (T)/h, respectively. Adjusting for differences in testicular weight did not eliminate significant (P less than 0.01) species variation in testicular capacity for T secretion in response to ovine LH. Similarly, correction for Leydig cell mass, as determined by morphometric analysis, still left significant (P less than 0.01) differences in the testosterone secretion rates in response to ovine LH for guinea pigs (262.5 +/- 38.6 micrograms T/g Leydig cell), rabbits (205.5 +/- 50.7 micrograms T/g Leydig cell), dogs (116.4 +/- 14.8 micrograms T/g Leydig cell), rats (83.55 +/- 21.80 micrograms T/g Leydig cell), and hamsters (18.24 +/- 3.55 micrograms T/g Leydig cell). The data suggest that significant between-species variation of T production in response to ovine LH is not due to quantitative differences in the mass of Leydig cells.

Animals↗

Age-related changes in conversion of 5 alpha-androstan-17 beta-ol-3-one to 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol by rat testicular cells in vitro.

Conversion of labelled 5 alpha-androstane-17 beta-ol-3-one (DHT) by isolated testicular cells from rats of different ages was examined under saturating substrate conditions in vitro (5--10 micrograms DHT/ml in a 24 h incubation). Two detectable metabolites of DHT were produced by testicular cells in vitro. 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol). Production of these diols during a 24 h period was linear, and the amounts formed were directly related to the cell number. The amount of 3 alpha- and 3 beta-diols formed by testicular cells of rats of different ages increased from Day 10 to Day 25, then declined. Testicular cells from rats 10 to 20 days of age converted DHT mainly to 3 alpha-diol, but thereafter 3 beta-diol was the predominant testicular metabolite of DHT.

Aging↗

Simultaneous determination of testosterone, 5alpha-androstan-17beta-ol-3-one, 5alpha-androstane-3alpha,17beta-diol and 5alpha-androstane-3beta,17beta-diol in plasma of adult male rabbits by radioimmunoassay(1).

A simultaneous radioimmunoassay procedure for plasma testosterone (T), 5alpha-androstan-17beta-ol-3-one (DHT), 5alpha-androstane-3alpha,17beta-diol (3alphaol), and 5alpha-androstan-3beta,17beta-diol (3betaol) is described in this report. Peripheral plasma concentrations of T, DHT, 3alphaol, and 3betaol were 1.16 +/- 0.26, 0.49 +/- 0.15, 0.17 +/- 0.03, and 0.24 +/- 0.04 ng/ml, respectively, in adult male rabbits. In contrast, T, DHT, 3alphaol, and 3betaol peripheral plasma concentrations in dexamethasone-treated castrate rabbits were 0.07 +/- 0.01, 0.02 +/- 0.01, 0.07 +/- 0.01, and 0.05 +/- 0.01 ng/ml, respectively. These results represent the first simultaneous measurement of T, DHT, 3alphaol, and 3betaol in peripheral plasma of any male vertebrate. Moreover, we suggest that DHT, 3alphaol, and 3betaol represent the unidentified immunoreactive material found in peripheral plasma of male rabbits by Falvo and Nalbandov (1).

Androstane-3,17-diol↗

Some factors affecting testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol secretion by invitro perfused rabbit testes.

Intra-arterial infusion of testosterone-3H gave rise to tritiated dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3beta,17 beta-diol in spermatic venous effluent of the perfused rabbit testis-epididymis. Mass spectrometric measurements confirmed that these four androgens were present in spermatic venous effluent of the perfused rabbit testis-epididymis. Gas liquid chromatographic measurement showed that testosterone, dihydrotestosterone, 5 alpha-androstan-3 alpha,17 beta-diol and 5 alpha-androstan-3 beta,17 beta-diol were secreted in similar amounts by the in vitro perfused and in situ rabbit testis-epididymis results obtained by perfusing the testis minus the epididymis suggested that the bulk of these androgens originate from the catabolism of testosterone within the testis rather than the epididymis. Suprisingly, germinal epithelium destruction by heat failed to alter the testosterone, dihydrotestosterone and 5 alpha-androstan-3 alpha,17 beta-diol secretion by the in vitro perfused rabbit testis. In contrast, the secretion of 5 alpha-androstan-3 beta,17 beta-diol was significantly (P less than 0.05) reduced in the same cryptorchid compared to control testes.

Androstane-3,17-diol↗