Production of an international reference standard alternaria extract. I. Testing of candidate extracts.

As part of a program to establish international standards of selected allergens, 6 coded extracts of Alternaria were assessed in 6 laboratories by immunochemical, biochemical and physicochemical procedures. Direct RAST, RAST inhibition, quantitative skin tests and leukocyte histamine release were used to assign relative orders of potency to the 6 extracts. The composition and major allergen content was tested by thin-layer isoelectric focusing and quantitative immunoelectrophoresis (crossed immunoelectrophoresis and crossed radioimmunoelectrophoresis). Three laboratories determined the quantity of purified allergens in each of the preparations. In addition, source materials were sent to an expert Alternaria taxonomist for independent identification. The results showed considerable variation with respect to total allergenic potency and content of individual allergens. Source materials could not be confirmed as Alternaria in some instances. Based on fulfillment of written specifications and assay results, extract No. 6 was recommended by the Alternaria Working Group as the candidate international standard to the Steering Committee of the Allergen Standardization Subcommittee of the International Union of Immunological Societies.

Testosterone metabolism by the prostate of the aging canine.

Examination of testosterone metabolism in the dorsal, lateral, and ventral regions of the beagle prostate showed an absence of regional heterogeneity for testosterone metabolite production and metabolic capacity. Testosterone metabolism by the hyperplastic prostate of aged beagles (11.1 years old) was distinguished from that of young mature (2.5-year-old) and mature adult (4.5-year-old) beagle prostate by increased reductive metabolism. The change was principally the consequence of increased production of 5 alpha-dihydrotestosterone and decreased production of 4-androstenedione. These alterations in testosterone metabolism occurred progressively and may be weakly linked to other changes in canine prostate which occur during aging. 5 alpha-Androstane-3 alpha, 17 beta-diol production was maximal for prostate from 4.5-year-old beagles and the amount of this metabolite produced appeared to be unrelated to prostate size. Co-incubation of prostate from any of the beagles with testosterone and estradiol showed that estradiol had no in vitro effect upon testosterone metabolism. Mean plasma testosterone content of aged beagles (11.1 years old) was not significantly different from that of younger individuals; however, the heterogeneity of the values for the subject groups was notable. The data demonstrate that the consequences of aging upon testosterone metabolism by canine prostate, which principally develops benign prostatic hyperplasia, are opposite to those characteristic of senescent rat prostate, which does not develop bening prostatic hyperplasia and has a high incidence of spontaneous adenocarcinoma.

Testosterone metabolism by the prostate of the aging AXC rat.

Testosterone metabolism by the ventral prostate of inbred, senescent (36-month-old) AXC rats showed a shift to increased oxidative and diminished reductive metabolism when compared to young mature (3-month-old) or mature adult (6-month-old) AXC rats. The change was principally attributable to diminished production of 5 alpha-dihydrotestosterone and increased production of 4-androstenedione. By contrast, dorsolateral prostate testosterone metabolism in these same rats was always more reductive than that of ventral prostate and failed to show the post-maturation shift to oxidative testosterone metabolism which characterized ventral prostate. Co-incubation of either ventral or dorsolateral prostate from any of these rats with testosterone and estradiol showed that estradiol did not significantly affect prostate testosterone metabolism. Plasma testosterone content of senescent AXC rats was only 28% of that of mature adult rats. Chronic exogenous testosterone treatment enhanced reductive testosterone metabolism by ventral prostate and eliminated those changes in metabolite distribution which had differentiated testosterone metabolism by young and senescent AXC rats. The data support the interpretation that the aging-related diminution in AXC rat ventral prostate reductive metabolic capacity is primarily the consequence of diminished 5 alpha-dihydrotestosterone production secondary to diminished plasma testosterone content.

C19-steroid metabolism by spontaneous adenocarcinoma of the A X C rat ventral prostate.

Specimens of ventral prostate from 37- to 46-month-old Andradurin-treated A X C rats demonstrated three primary morphologic patterns, each being divisible into two sub-groups based upon the extent of glandular alteration. The principal groups were: group 1, hyperplasia; group 2, atypical hyperplasia; and group 3, adenocarcinoma. The secondary classifications were: subgroup (+), few glands involved; and subgroup (++), most glands involved. Multiple parameters of ventral prostate testosterone metabolic potential failed to distinguish the morphologically diverse prostate specimens of groups (1+). 1(++), 2(+), 2(++), and 3(+) which predominantly metabolized testosterone to 5alpha-reduced 17beta-hydroxysteroids. By contrast, testosterone metabolism by ventral prostate specimens predominantly composed of neoplastic epithelium, group 3(++), was distinct from all other prostate specimens. The distinguishing feature was a shift to more prominent elaboration of 17-ketosteroids, principally delta4-androstenedione, and a cteroids. The change in this biochemical parameter of prostate epithelial cell function was indicated to be an early manifestation of the neoplastic transformation.

Biotransformation of pregnenolone - 7alpha-3H, progesterone - 7alpha-3H and dehydroepiandrosterone - 7alpha-3H by porcine fetal and maternal adrenal homogenate preparations.

The biotransformation of pregnenolone-7alpha-3H and of progesterone-7alpha-3H by porcine fetal and maternal adrenal homogenates at 56 and 112 days of pregnancy and of dehydroepiandrosterone-7alpha-3H by fetal adrenal homogenates has been investigated in vitro. Both pregnenolone-7alpha-3H and progesterone-7alpha-3H were metabolized extensively by maternal adrenal preparations, the principal radioactive metabolites isolated being cortisol, corticosterone, 11-deoxycortisol, deoxycorticosterone, 11beta-hydroxyprogesterone and androstenedione. In addition, 17alpha-hydroxyprogesterone, 20alpha-dihydroprogesterone and cortisone were formed from both substrates and 17alpha-hydroxypregnenolone and progesterone were formed from pregnenolone. Although essentially the same radioactive metabolites were isolated after incubation of fetal adrenal glands with pregnenolone-7alpha-3H or progesterone-7alpha-3H, a greater proportion of the radioactivity was associated with corticosteroids at 112 days of pregnancy than at 56 days. 11beta-Hydroxyandrostenedione and androstenedione were isolated and identified together with an unknown polar metabolite, after incubation of fetal adrenal tissue with dehydroepiandrosterone-7alpha-3H. These results are discussed in relation to feto-placental steroid biosynthesis and metabolism and the role of the fetal adrenal in the initiation of parturition in the pig.