Testicular feminization

Androgens act via the AR and play an important role in the development and differentiation of the male sexual organ. Furthermore, they are involved in several diseases, the most important being partial and complete androgen insensitivity syndrome (AIS formerly known as the testicular feminization syndrome), spinal and bulbar muscle atrophy (SBMA Kennedy s disease), and the neoplastic transformation of the prostate. The two natural occurring androgens are testosterone (T) and the... 

The fact that we all begin life basically as females can be appreciated in several ways. For example, if the testes are removed from an embryonic male fetus, the individual is bom female. Males lacking functional androgen receptors provide a second example these individuals are phenotypicaUy female, a phenomenon known as testicular feminization. It follows that embryonic mammals are targeted to become females unless androgens intervene in the development and differentiation process. 

Several inherited disorders that produce defective androgen receptors (androgen resistance) also cause disruption of sexual development that may culminate in infertility or testicular feminization. 

Testicular feminization is characterized by expression of a female external phenotype despite a normal blood level of testosterone and standard male karyotype (46,XY). 

The answer is D. The patient s ambiguous secondary sex characteristics and lack of menstrual activity suggest the possibility of an androgen resistance syndrome. The male karyotype and blood testosterone levels confirm this. This clinical condition might have arisen as a result of steroid 5oc-reductase deficiency or inherited defects in the androgen receptor (testicular feminization). 

Steroid hormonal dysfunctions, including male pseudobermaphru ditism and testicular feminization. 

The effect of androgens is promoted by various metabolites in a very subtle manner, subject to significant developmental change. It is currently advocated that 5j8-reduced metabolites act directly on erythropoietic stem cells, whereas 5 -reduced derivatives enhance the level of erythropoietin. Interestingly, mutant mice with testicular feminization (TfmlY) actively maintain erythropoiesis, suggesting that androgenic effects on red cell formation are not mediated by conventional receptor mechanisms antiandrogens are either of variable or no influence. 

Other studies have shown that mouse kidney contains a receptor system specific for testosterone and this is lost in the testicular feminization mutant. Certainly, androgens are primarily responsible for the induction of /3-glucuronidase, but part of the response could be attributable to progesterone receptors. In this context, var-... 

Complete androgen insensitivity (testicular feminization) Incomplete androgen sensitivity Androgen receptor defects 5a-Reductase deficiency... 

XO gonadal and X dysgenesis and variants XX gonadal dysgenesis Turner s syndrome Testicular feminization syndrome 17-Hydroxylase deficiency of the ovaries and adrenal glands... 

Other endocrine causes of infertility include exogenous androgens, thyroid disorders, adrenal hyperplasia, and testicular failure. Gynecomastia or obesity in the infertile male may signify elevated concentrations of estrogen and possibly testicular feminization syndrome (see earlier section on male reproductive abnormalities). ... 

Other proteins needed for normal male development include the X-linked androgen receptor, whose absence causes testicular feminization, and dihydrotestosterone reductase (Chapter 22). 

In a condition known as testicular feminization, patients produce androgens (the male sex steroids), but target cells fail to respond to these steroid hormones because they lack the appropriate intracellular transcription factor receptors. Therefore, the transcription of the genes responsible for masculinization is not activated. A patient with this condition has an XY (male) karyotype (set of chromosomes) but looks like a female. External male genitalia do not develop, but testes are present, usually in the inguinal region. 

In the X-linked recessive mutations in man and several other species often designated as the testicular feminization or androgen-insensitivity syndrome, complete or partial resistance to endogenous androgens, and to exogenous testosterone or dihydrotesterone, is man-... 

Fig. 8.12. Ovarian dysgenesis in testicular feminization. In a phenotypical 55-year-old woman no uterus can be identified. A soft tissue attenuation mass (asterisk) near the internal inguinal ring presents a left streak gonad. Histologically proven...

Tauri disease Tay-Sachs disease Testicular feminization syndrome Tetrahydrobiopterin deficiency Thiopurine methyltransferase deficiency Thymidine phosphorylase deficiency Transcobalamin II deficiency Tricho-hepato-enteric syndrome Trimethylaminuria Tripeptidyl peptidase I deficiency Tryptophan-2,3-dioxygenase deficiency Tryptophanuria... 

Further reading Wilson, J.D. and Macdonald, P.C. (1978). Male pseudohermaphroditism due to androgen resistance Testicular feminization and related syndromes. In Stan-bury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease. 4th Edn., p. 894. (New York McGraw-Hill)... 

Androgen insensitivity syndrome (AIS) is also called testicular feminization and results from a complete or partial absence of cytoplasmic receptors for testosterone in target tissues (Holterhus et al. 2005). It is an X-linked (handXqll-ql2) disorder with an inci-... 

Tfm sex-linked male mutants have lost their inducibility, although they have testis and are phenotypically similar to females (testicular feminization). The mechanism of expression of this mutation is associated with a product which is controlled by the Tfm locus. As a result of lost competence to testosterone, Tfm/Y males are characterized by noninducibility (Ohno, 1971 Ohno and Lyon, 1970 Ohno et al., 1970). Later it was demonstrated that the corresponding operator (O ) of a noninducible mutant of j8-glucuronidase is associated with the slow isozyme of this enzyme. The result of this experiment confirmed that the translation repressor determined by the Tfm locus recognize the translated segment of mRNA (Dofuku et al., 1971). 

---