Walter Nienstedt

Metabolism of testosterone by human healthy and inflamed gingiva in vitro.

Abstract Testosterone was incubated with homogenate and mitochondrial, microsomal and soluble-fraction preparations of healthy and inflamed gingiva in human subjects of both sexes. In the inflamed preparations, the metabolic activity was higher than in the samples from healthy gingiva. The gingiva contained the following enzymic activities: Δ 4 -5α-steroid hydrogenase, Δ 4 -5β-steroid hydrogenase, and 3α-, 3β- and 17β-hydroxysteroid dehydrogenase, principally in the soluble fraction. Mitochondrial and microsomal preparations were less active. Both the healthy and especially the inflamed samples were able to convert testosterone to 17/gb-hydroxy -5α-androstan-3-one, suggesting that gingiva may be a target tissue for androgens.

Metabolism of testosterone in the isolated perfused rat lungs

Abstract The metabolism of [4-14C]-testosterone in the isolated perfused rat lungs was investigated following the administration of the substrate eithervia the pulmonary artery orvia the trachea. After administration of testosterone in the circulating medium, 3.5% of the hormone was metabolized to various unconjugated metabolites during a single passage through the pulmonary circulation. It so seems that the lungs, receiving all the cardiac output, are one of the major sites of androgen catabolism in the rat organism. The major metabolites were 5α- and 5β-androstane-3α,17β-diols and various non-conjugated polar metabolites. After intratracheal instillation, testosterone was rapidly absorbed from rat lungs. Two minutes following installation, 62% of the dose was recovered from the lungs. Two thirds of this was present as metabolites. It is concluded that the lungs have an efficient metabolic capacity towards androgens. The availability of extractable substrate seems to be rate limiting for the pulmonary testosterone metabolism.

Metabolism of progesterone, 17-hydroxyprogesterone and deoxycorticosterone by human small intestine in vitro

Abstract Homogenized intestinal samples from two adult human males and 13 human fetuses of both sexes (crown-heel lengths 15–200 mm) were incubated with [4-14C]-progesterone. In addition homogenized intestinal tissue from one fetus was incubated with [4-14C]-17-hydroxyprogesterone and [4-14C]-deoxy-corticosterone. The adult intestinal homogenate produced mainly 5α-reduced metabolites, which is in agreement with results obtained earlier with canine intestine. The fetal intestinal metabolism was qualitatively different, as predominantly (or only) 5β-reduced metabolites were formed. The smallest fetuses had the most active metabolism when calculated on tissue weight basis.

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the hepatic metabolism of testosterone in the rat.

A dose of 20 micrograms/kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was given to adult male rats intragastrically and the metabolism of [4-14C]-testosterone by liver homogenate was examined 1 week later. The overall catabolism of testosterone was significantly reduced by the TCDD treatment. Dihydroxysteroids (intermediate reduced metabolites) were increased, while the production of polar non-conjugated metabolites (end products) was diminished.

Metabolism of estradiol in isolated perfused rat lungs

The metabolism of [4-4C]-estradiol in isolated perfused male rat lungs was investigated. The substrate was applied either via the trachea or via the pulmonary artery. The metabolites of estradiol were analysed from the perfusion media and pulmonary tissue with column and thin layer chromatography and liquid scintillation counting. Compared to testosterone and progesterone, which have been studied earlier in similar experiments, estradiol was metabolized considerably slower. The main metabolite formed was estrone.

The effects of cigarette smoke exposure on testosterone metabolism in the isolated perfused rat lung.

Abstract Rats were exposed daily to cigarette smoke for 1 h for five consecutive days. The metabolism of [4- 14 C]-testosterone by the isolated perfused lungs was studied on the sixth day. Slightly diluted rat blood. containing the radioactive substrate, was used as the perfusion medium. Compared to sham-exposure rats, the formation of reduced metabolites (dihydroxysteroids) was less and the metabolism of testosterone diminished after cigarette smoke exposure. After the perfusion the amount of polar non-conjugated metabolites was significantly higher in the smoke-exposed lung tissue than in the control lungs. No conjugate formation was observed. The decrease in the formation of reduced metabolites seems to be due to an inhibition of the 4-ene-5α-reductase activity.

The metabolism of testosterone by human, rabbit and rat kidney

Abstract 1. 1. The metabolism of testosterone by the homogenate, microsomal and soluble fractions of human, rabbit and rat kidneys was investigated. Human kidneys were obtained from patients who underwent surgery for cancer, and the metabolism of testosterone was investigated using the intact part and in some cases also the cancerous part. 2. 2. Testosterone was metabolized by the homogenate and microsomal preparation of male and female human and male rat kidneys to androstenedione (4-androstene-3,17-dione) and to a lesser extent to monohydroxymonoketosteroids, dihydroxysteroids and to more polar metabolites. The main metabolites in the soluble fraction were dihydroxysteroids of the 5β-series. 3. 3. The rabbit kidneys differed from human and rat kidneys by showing a much greater rate of testosterone metabolism and by producing epitestosterone—via androstenedione—as a major metabolite. The formation of epitestosterone was especially marked in the homogenate of rabbit kidney.

Metabolism of testosterone in human lung in vitro

Abstract 1. 1. The metabolism of 4-14C-testosterone in human lung in vitro was investigated. 2. 2. The metabolism was most pronounced in incubations of homogenated tissue, whereas it was rather restricted in the mitochondrial, microsomal and soluble fraction incubations. 3. 3. The by far most prominent metabolite in all experiments was androst-4-ene-3,17-dione. 4. 4. No slfate or glucuronide conjugation took place.

Metabolism of testosterone and androstenedione by human adult and fetal gastrointestinal tissues in vitro

Abstract Homogenized gastric, duodenal and ileal mucosa samples from adult male humans were incubated with [4-14C]-testosterone or [4-14C]-androstenedione. In addition soluble fractions of adult male human gastric or intestinal mucosa were incubated with [4-14C]-testosterone. Intestinal homogenates from several human fetuses of both sexes (crown-heel lengths 50–210 mm) were incubated either with [4-14C]-testosterone or [4-14C]-androstenedione. Only 5α-reduced metabolites could be detected after adult homogenate incubations and only 5β-reduced forms after soluble fraction incubations. The fetal intestines showed great interindividual variation and produced either 5α-metabolites or both 5α- and 5⨿-metabolites. Quantitatively, on tissue weight basis, the smallest fetuses metabolized testosterone and androstenedione with a capacity at least equal to the oldest ones. With adult intestinal homogenates the metabolism seemed to increase towards the aboral direction of the gastrointestinal tract.

Metabolism of testosterone and progesterone by gastrointestinal tissues of the pike (Esox lucius)

[4-14C]Testosterone and [4-14C]progesterone were incubated with homogenates of liver and of esophageal, gastric, and intestinal mucosa of the pike (Esox lucius). The esophageal and gastric incubations produced both 5α- and 5β-reduced metabolites, but only 5β-reductase was found in the intestinal and hepatic incubations. The metabolism in the intestinal and hepatic samples was almost identical both qualitatively and quantitatively and more active than that in the esophageal and gastric samples. The pattern of pike intestinal metabolism differs from that observed in a number of mammalian species.