Steroid hormones during development

Testosterone, the principal male sex steroid hormone, is synthesized in five steps from cholesterol, as shown below. In the last step, five isozymes catalyze the 17/3-hydroxysteroid dehydrogenase reactions that interconvert 4-androstenedione and testosterone. Defects in the synthesis or action of testosterone can impair the development of the male phenotype during embryogenesis and cause the disorders of human sexuality termed male pseudohermaphroditism. Specifically, mutations in isozyme 3 of the 17/3-hydroxysteroid dehydrogenase in the fetal testis impair the for-... 

During development, steroid-hormone receptors become evident in target neurons of the brain 854... 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

Three adolescent boys with chronic renal insufficiency, treated with somatropin during the pubertal growth spurt, developed severe hyperparathyroidism (35). It is unclear whether this was coincidental or whether growth hormone and sex steroid hormones had a synergistic effect. 

In 1948, Edward C. Kendall, who clarified steroid structures during the 1930s (see chapter 4), and Philip S. Hench (1896-1965), at the Mayo Clinic, demonstrated that the steroid hormone cortisone relieves symptoms of rheumatoid arthritis. Kendall, Hench, and Tadeus Reichstein would share the 1950 Nobel Prize in physiology or medicine. Although Lewis Sarett (1917-99) at Merck had accomplished a total synthesis of cortisone in 1944 (Woodward published a more elegant one in 1951), cortisone and its close derivatives would have remained extremely expensive were it not for the efforts of Percy L. Julian (1899-1975). As soon as he learned of the Mayo Clinic discovery, Julian developed a rapid, inexpensive synthesis of Reichstein s Substance S, also isolated ftom the adrenal cortex. This steroid is easily converted to dihydrocortisone and Julian s pathway remains today the major commercial route to this over-the-counter topical remedy for sunburn, mosquito bites, and other uncomfortable skin irritations. 

Finally, steroid hormones, retinoic acid, eicosanoids, some NEFA, etc., can bind to nuclear receptors to activate transcription factors. For instance, retinoic acid can activate retinoic acid receptor to control differentiation and proliferation of many types of cells during development [53]. 

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