Human Biochemistry Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Sex Gland Hormones
Pathophysiology of the Male Reproductive System

A decrease in testosterone synthesis is referred to as hypogonadism. In prepubertal individuals, hypogonadism prevents The Development of secondary sex characteristics. Conversely, when hypogonadism develops in adult males, these characteristics undergo regression. Primary hypogonadism results from pathological processes that directly affect the Testes and cause testicular insufficiency. Secondary hypogonadism is caused by impaired gonadotropin secretion. The Study of hereditary disorders helps elucidate The Role of specific stages in androgen Biosynthesis and function. Figure 50.5 illustrates the MECHANISM OF ACTION of these Hormones, ranging from testosterone biosynthesis to the post-receptor effects of testosterone and DHT. Currently, at least five distinct Genetic Defects in testosterone biosynthesis are known, and $5\alpha$-reductase deficiency has been described. In many cases, the testosterone/DHT receptor is either completely undetectable or structurally altered. Finally, patients (all with a male genotype) have been identified in whom all measurable components, including the receptor, are normal, yet who exhibit feminization. The degree of differentiation impairment depends on the severity of the deficiency. For instance, the complete absence of one of the biosynthetic Enzymes results in a female phenotype in individuals with a male (XY) genotype, whereas moderate enzyme deficiency may manifest merely as hypospadias. Genetic males completely lacking functional receptors possess testes and produce testosterone, yet exhibit complete feminization of the external genitalia (known as testicular feminization syndrome). Interestingly, no analogous deficiency in estrogen synthesis or activity has been discovered.

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Fig. 50.5. Causes of absent androgen action. Four stages are shown, with identified Mutations for each. T — testosterone, DHT — dihydrotestosterone, R — androgen receptor. (Modified and reproduced, with permission, from Wilson J. D. et al. The endocrine control of male phenotypic development. Aust J. Biol. Sci. 1983, 36, 101.)