Hormonal and clinical aspects of hermaphroditism and the testicular feminizing syndrome in man

Abstract

Intersexual conditions in man may be classified, on the grounds of the gonadal make up, into two groups: true and pseudohermaphrodites. The former have ovarian and testicular tissue, while in the latter only one type is found (female and male varieties). In one quarter or more of true hermaphrodites there is chromosome mosaicism and the presence of a Y chromosome in at least one of the cell lines, in most cases, explains the error of sex determination. However, in the many 46, XX and in the fewer 46, XY cases, the origin of the gonadal intersexuality is not clear, though both genetic and epigenetic influences may be at work. It would seem that, as a result of abnormal development, the right gonad would more easily be transformed into a testis and the left into an ovary. In many pseudohermaphrodites, the anomaly of sex differentiation results from an inherited abnormality of adrenal steroidogenesis acting on the sex structures during embryonic development and persisting during postnatal life. A relatively common form of male pseudohermaphroditism is the syndrome of testicular feminization. This is characterized by a perfectly feminine body habitus but absence of sex hair and of uterus, and by extreme hypoplasia, or absence, of Mullerian or Wolffian derivatives. The gonads, often intra-abdominal, are testes, usually sterile. The overall evidence is that these testes produce testosterone, probably at normal male levels, and possibly oestrogens in a similar fashion, though the intra-abdominal situation of the gonad and some variables of its structure, of the clinical condition and of the techniques used may underly the variability of the findings. Evidence supports the idea that the condition is caused by targetorgan resistance, which seems to rest on the inability of the target organs to convert testosterone into dihydrotestosterone, which appears to be concerned with the androgen response of the target organs. This same lack of responsiveness during embryonic development would account for failure of male differentiation, and such a mechanism would support the idea that the normal foetal male hormone is testosterone. The conversion normally appears to be controlled by a specific 5a-reductase and, in view of the fact that testicular feminization is an inherited condition seemingly caused by point mutation, it is possible that the enzyme itself may be abnormal or absent. The exact mode of inheritance of testicular feminization is unknown. Linkage studies so far have not resolved between sex-linked and autosomal sex-limited transmission, though the presence of a demonstrable biochemical defect may now help in resolving the point at issue.