lesson22 - 22 Module 3 Review Troublesome Concepts Gonadal...

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22 Module 3 Review Troublesome Concepts Gonadal hormones . Despite numerous warnings, some of you will persist with the idea that testosterone leads to the development of male characteristics and estradiol leads to the development of female characteristics. This is very logical and it has an appealing symmetry to it. The only thing wrong with it is that it’s wrong! The simple, asymmetrical fact of the matter is that both testosterone and estradiol lead to the development of male characteristics. Testosterone does so by first being converted to estradiol inside cells. Estradiol inside of cells leads to a pattern of gene expression (and therefore to an array of proteins) that brings about male development. The tricky part, then, if female development is to proceed, is to keep estradiol from getting into cells. Estradiol is kept out of cells in two ways. First, alpha-fetoprotein binds to estradiol molecules that are encountered in the bloodstream. As long as estradiol is present only in normal, fairly limited quantities, this works beautifully. The second way of keeping estradiol out of cells is to not produce testosterone! That’s right. Since testosterone is immune from alpha- fetoprotein blockade, it can get into cells. Once inside, testosterone is converted by an enzyme into estradiol, which, as we’ve seen, can get right to work on influencing gene expression. (Alpha-fetoprotein is not found inside cells, so is not effective at preventing estradiol’s effect on gene expression.) Differentiation disorders . Sexual differentiation is a complicated set of processes, so things can go wrong. We discussed only three of the many disorders associated with sexual differentiation, two that affect females and one that affects males. Both congenital adrenal hyperplasia (CAH) and the use of synthetic estrogens by pregnant women (the most common of which is diethylstilbestrol or DES) can masculinize female fetuses. CAH has a masculinizing effect because of the production of larger quantities of androgen hormones than would normally be present in females. DES has a masculinizing effect because the artificial estrogens are not bound up as effectively by the alpha-fetoprotein. The extent of the masculinization varies from one case to the next, depending on the amount and timing of the hormone within the developing fetus. Further, since there are different sensitive Lesson 22 249
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periods for different parts of the brain and body, there can be masculinization of certain features (e.g., brain and later behavior) but not others (e.g., external genitalia). The condition that interferes with male differentiation is known as androgen insensitivity syndrome. In androgen insensitivity, the male fetus produces testosterone but his testosterone receptors are defective. Consequently, testosterone cannot enter cells and none is available for conversion to estradiol. Without intra-cellular estradiol to trigger masculine patterns of gene expression, development of the affected individual proceeds in the female direction. (The small
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This note was uploaded on 05/27/2010 for the course BIOS 373 B02 taught by Professor Dr.danielleger during the Spring '10 term at UNL.

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lesson22 - 22 Module 3 Review Troublesome Concepts Gonadal...

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