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U Drews

Publications and source records attributed to U Drews.

At least 73 records · Page 4Linked to original sources

Cell death in the mosaic epididymis of sex reversed mice, heterozygous for testicular feminization.

Sex reversed mice heterozygous for testicular feminization are genetic females which are converted to males by the autosomal Sxr ("sex reversed") mutation, thus imitating the Y-chromosome. They carry on one of their X-chromosomes the mutation for testicular feminization. Then, X-inactivation leads to the formation of a mosaic of androgen insensitive XTfm and androgen sensitive X+ cells. In the epididymis the Tfm cells are maintained into adulthood as undifferentiated flat cells. There are however, always less Tfm cells than expected from random X-inactivation. Therefore, in the present study the role of cell death in the modification of the original mosaic is investigated before and after castration. It is shown that survival or elimination of Tfm cells depends on the structure of the smooth muscle layers around the epididymal duct. In addition to elimination of whole Tfm sections, a steady loss of single cells, not only in the Tfm but also in the wild-type fraction occurs. In the connective tissue distinct necrotic areas are present. After castration massive necroses appear in both cell types. In Tfm sections disintegration of the wall layers again leads to elimination of Tfm cells and to protrusion of epithelial cells in the interstitium which later on may be organized as abnormal sprouts and ducts. The observations indicate that the testosterone dependent trophic principle is based on short-range intercellular interactions and presumably arises in the connective tissue component of the epididymis.

Androgen-Insensitivity Syndrome↗

Regression of mouse mammary gland anlagen in recombinants of Tfm and wild-type tissues: testosterone acts via the mesenchyme.

In the male mouse, regression of the mammary gland anlagen is induced by testosterone during embryonic life. In the androgen-insensitive Tfm mouse, the gland anlagen are resistant to the testosterone action. To analyze cellular interactions in this process, we isolated the mammary gland anlagen from Tfm- and wild-type embryos. The epithelial buds were separated from the mesencyme by trypsin-pacreatin treatment. From the epithelial and mesenchymal components, reciprocal recombinations were prepared and cultivated on millipore filter in the presence of testosterone. In combination with androgen-insensitive Tfm- mesenchyme, the wild-type buds survived the action of testosterone. On the other hand, in combination with wild-type mesenchyme, the androgen-insensitive Tfm epithelial buds were destroyed. The results show that testosterone induces detachment and degeneration of the buds via the mesenchyme.

Animals↗

[Sexually differentiated metabolism of testosterone in liver slices of mouse, and its alteration by a mutation in the X-chromosome that results in testicular feminization].

1. Sexual differentiation of the metabolism of testosterone in liver slices of normally developed, sexually mature mice: Sexual differentiation in the mouse, unlike that in the rat, shows a high degree of uniformity: Where the formation of metabolites with the composition C19O2 is markedly greater in one sex, then this is invariably the male. The formation of C19O3 steroids and 4-androstene-3,17-dione, and the turnover of testosterone show no marked sexual differences, although the sum of the C19O2-type delta4-hydrogenation products of testosterone is significantly greater in the male. This apparent discrepancy is explained by the fact that the sum of the delta4-hydrogenation products represents no more than 10% of testosterone turnover. Thus, sexual differences in the formation of individual delta4-hydrogenation products are not apparent from a consideration of the overall turnover of testosterone. 2. Sexual differentiation of testosterone metabolism studied in genetically male litter mates, carrying the X-chromosome-bound mutation and showing testicular feminization (Tfm): The Tfm mutation (genotype XTfm Blo/Y; Blo = coat colour gene Blotchy) results in a feminization of testosterone metabolism. Where the level of testosterone metabolites is significantly higher in the normal male than in the normal female, the Tfm mutation shows a level that is significantly lower than in the normal male, and which, in most cases, is the same as that in the normal female. The concentration of three metabolites (3alpha- and 3beta-hydroxy-5beta-androstan-17-one, and 5beta-androstane-3,17-dione), which do not show sex-based differences, were significantly increased in the Tfm mutation. The Tfm mutation therefore effects the formation of all ring A hydrogenation products of type C19O2 (with the single exception of 5bets-androstane-3alpha,17beta-diol). It does more than simply equalize sexual differences by feminization. It has no effect on the hydroxylation of testosterone, or on its 17beta-dehydrogenation to 4-androstene-3,17-dione. The consequences of the Tfm mutation for the liver are irreversible: The formation of 5alpha-androstane-3,17-dione, which is a representative parameter for the sexual differentiation of testosterone metabolism, is not influenced by the injection of testosterone (15 mg i.p. 6 days before investigation).

Androgen-Insensitivity Syndrome↗

Direct and mediated effects of testosterone: the development of intersexes in sex reversed mosaic mice, heterozygous for testicular feminization.

The X-linked Tfm mutation causes androgen insensitivity in the target cells of testerone. Due to random X-inactivation, XX-mice heterozygous for Tfm are mosaics in respect to androgen sensitivity. By the autosomal "sex reversal" mutation, Tfm-heterozygotes were converted to males during embryonic life so that male sex organs developed in which the mosaic was expressed. The mutual influence of both components of the mosaic is analysed. It is shown that cellular differentiation is directly induced by testosterone, while the formation of organ anlagen and proliferation are locally mediated effects.

Androgen-Insensitivity Syndrome↗

Cholinesterase in embryonic development.

I. Cholinesterase (ChE) activity was studied histochemically during early development of the sea urchin, the amphibian, the chick and the rat embryo. After formalin fixation and embedding in water-soluble carbowax, the enzyme reaction was carried out in serial section. 2. Independent from innervation ChE appears in every embryonic blastema in a very early stage of development. It disappears from the embryonic cells after they have assembled into definite organ structures. Thus, ChE plays a role in embryonic development which is different from its known function in the adult. Therefore, ChE activity present in differentiating cells during a limited phase of development, is termed "embryonic cholinesterase". 3. Embryonic ChE was invariably found in cells engaged in morphogenetic movements. This observation has led us to suppose that the enzyme in involved in the regulation of cellular movements during development. 4. In particular, embryonic ChE is described in the following locations: a) During sea urchin gastrulation ChE is present in the primary mesenchymal cells emigrating from the blastula wall and in the archenteron cells which are known to bring about the invagination movement by contraction of their pseudopods. b) In the early chick blastoderm ChE active "droplet cells" are described which are supposed to emigrate from the epiblast layer in order to form the hypoblast. c) During development of notochord and somites, during closure of the neural tube and development of the head anlage, the close correlation of ChE activity with various morphogenetic movements is demonstrated: ChE appears during aggregation and desaggregation of epithelial compounds. The active bending of preexisting epithelial sheets, such as the neural plate, is also accompanied by ChE activity in epithelial cells...

Acetylcholinesterase↗