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Biomedical subjects

U Wolf

Publications and source records attributed to U Wolf.

At least 91 records · Page 5Linked to original sources

XY gonadal dysgenesis and the H-Y antigen. Report on 12 cases.

H-Y antigen was determined in 12 patients affected by XY gonadal dysgenesis. Of these, three proved to be H-Y negative, and nine, including two sisters, were H-Y positive; two of the unrelated positive cases exhibited a reduced antigen titer. Therefore, this clinical condition must be genetically heterogeneous. It is assumed that in the negative cases and possibly in those with reduced antigen titer, the H-Y generating system is affected by mutation, while in the regular positive cases the target cells are unable to respond due to a defect of the gonad-specific H-Y antigen receptor.

Adolescent↗

Evidence for a gonad-specific receptor for H-Y antigen: binding of exogenous H-Y antigen to gonadal cells is independent of beta 2-microglobulin.

This report addresses the question whether two different types of binding exist for the reaction of H-Y antigen with the cell surface. Anti-H-Y antiserum in the presence of complement was cytotoxic only for gonadal cells expressing their own H-Y antigen, but not to ovarian cells loaded with H-Y antigen. H-Y antigen was co-redistributed with beta 2--microglobulin on newborn testicular cells, but some residual H-Y activity was found on similarly treated testis cells from 15 day old rats. After beta 2--microglobulin redistribution, testis cells maintained their binding capacity for exogenous H-Y antigen prepared from epididymal fluid or Daudi cell culture supernatants. This result suggests that exogenous H-Y antigen is bound via a gonad-specific receptor which is independent of beta 2--microglobulin and that this type of binding for H-Y antigen is different from the beta 2--m-associated expression of H-Y antigen on the cell surface.

Animals↗

Cross-reactivity to mammalian anti-H-Y antiserum in teleostean fish.

Anti-H-Y antiserum, raised in highly inbred rats, is absorbed by gonadal cells of various species of fish. This cross-reactivity proved to be restricted to the male sex in the cyprinodont species Lebistes and Xiphophorus, known to have the XX/XY mechanism of sex determination. In members of the more primitive fish orders Isospondyli and Ostariophysi, cross-reactivity was shown to occur as well, but the amount of antiserum absorbed was very similar in both sexes. An antigen cross-reacting with mammalian anti-H-Y antiserum is assumed to exist in fish similar to that found in higher vertebrates. If this is true, this antigen may have been shared originally by both sexes. However, during evolution, its expression has become restricted to the heterogametic sex.

Animals↗

Studies on H-Y antigen in different cell fractions of the testis during pubescence: immature germ cells are H-Y antigen negative.

Various cell types of the rat testis during pubescence, including germ, Sertoli, and Leydig cells, were partially enriched. The fractions were tested for the presence, binding, and secretion of H-Y antigen. The main results are: Immature germ cells are H-Y antigen-negative until the late diploid stages, and late primary spermatocytes or spermatids become positive; the somatic cells of the gonad are positive at all ages examined (18 days old to adulthood). Secretion of H-Y antigen is restricted to the Sertoli cell fraction. Binding of externally supplied antigen takes place on Leydig cells; the Sertoli cell surface will be saturated because of active secretion; there is no binding to germ cells. Thus, immature germ cells seem to be the only H-Y antigen-negative cells of the male organism, and the Sertoli cells seem to be the only ones to secrete H-Y antigen.

Age Factors↗

Appearance of hCG-receptor after conversion of newborn ovarian cells into testicular structures by H-Y antigen in vitro.

In a previous report (Zenzes et al., 1978b) it was shown that dissociated ovarian cells of newborn rats in vitro, if exposed to H-Y antigen, reorganize into testicular structures. The current study was designed to see whether this morphological conversion also results in a functional conversion. The LH/hCG receptor was used as a parameter characteristic for the newborn testis, but not for the newborn ovary. In the converted ovary, the LH/hCG receptor becomes detectable a few hours after onset of the culture and remains continuously present afterward. The appearance of this receptor may be due to a hormone-like action of H-Y antigen.

Animals↗

The testis as a secretory organ for H-Y antigen.

After cultivation of dissociated rat testicular tissues, H-Y antigen is detectable in the medium; this is not the case if nongonadal male tissues are incubated. Release of H-Y antigen by testis cells is inhibited by the addition of cycloheximide. All tissues still type H-Y positive after culture. It is assumed that the testis actively secretes H-Y antigen. This assumption is supported by the finding that the amount of H-Y antigen in the epididymal fluid increases with the age of the animals.

Animals↗

Organization in vitro of ovarian cells into testicular structures.

While it has been shown previously (Zenzes et al., 1978; Ohno et al., 1978) that when dissociated testicular cells are exposed to anti H-Y antiserum in vitro they are prevented from reorganizing into testicular structures, forming ovarian follicular structures instead, the most conclusive evidence for the action of H-Y antigen would be the conversion of ovarian cells into testicular organization. Testing for H-Y antigen of the medium collected from cultivated testicular cells revealed a positive reaction. Dissociated ovarian cells of newborn rats cultivated in this medium reorganize into testicular structures. It is concluded that H-Y antigen is responsible for this histomorphologic change.

Animals↗

Binding studies of H-Y antigen in rat tissues: indications for a gonad-specific receptor.

The binding capacity for H-Y antigen was studied in various rat tissues of both sexes. In nongonadal tissues (liver, kidney, brain, epidermis) binding could not be demonstrated. In contrast, the gonads are able to bind exogenously supplied H-Y antigen. In the ovary, the binding capacity remains unchanged in newborn and adult animals, while in the testis, this capacity decreases with age. A receptor like that of a proteohormone is assumed to exist in the gonads but not in other tissues. In nongonadal tissues, H-Y antigen apparently is present only if the cell itself synthesizes the antigen. The H-Y antigen receptor of the gonads is not sex-specific. Thus, the primary sex differentiation depends on whether H-Y antigen is synthesized in the organism.

Animals↗

Studies on the function of H-Y antigen: dissociation and reorganization experiments on rat gonadal tissue.

On circumstantial evidence, H-Y antigen is assumed to be responsible for the differentiation of the undetermined gonadal anlage into a testis. A direct approach to test the function of H-Y antigen is provided by Moscona-type experiments. Applying a modified technique of in vitro reassociation of cell suspensions, we obtained the following results: (1) dissociated newborn rat gonads, both testis and ovary, reorganize into histotypic structures; (2) under exposure to anti-H-Y antiserum, testicular cells reassociate into ovarian follicular-like organization; (3) anti-H-1 antiserum by itself does not prevent the testicular cells from forming tubular structures. It is concluded that H-Y antigen acts as a differentiation between preferably or exclusively on the cell elements participating in the formation of the seminiferous cords.

Animals↗

[The mechanism of gonadal differentiation].

The steroid-hormone dependent sexual development presupposes the already sex-specific differentiated gonads. The H-Y antigen is held responsible for the primary differentiation of the indifferent gonadal anlage towards testicular organization. Studies on the function of H-Y antigen, using gonadal cells in vitro, have shown that in the presence of H-Y antigen the gonad differentiates into testicular, in its absence into ovarian structures, independent of whether the sex chromosomes are XX or XY. The gonads of both sexes are endowed with a specific H-Y receptor, other tissues are not. The bipotency of the gonadal anlage arises from this character. Some disorders of sexual development presumably go back to mutations affecting the genetic control of the H-Y gene and the function of H-Y antigen, respectively. It is discussed that the Y chromosome may have a mere regulatory function and not include the H-Y gene. Thus, the primary differentiation of the gonad should be dependent exclusively on whether or not the H-Y gene is active.

Female↗