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Web Topic 5.4: Testosterone Conversion to Estradiol

[Referenced on textbook p. 130]

There are further experiments on rats that clarify how testosterone acts in the brain. If estradiol is injected into the hypothalamus of a castrated rat instead of testosterone, it works just as well in restoring normal intromission and ejaculation. If one injects DHT—a very potent androgen that cannot be converted to estradiol—no recovery is seen. These findings together suggest that, when testosterone enters the hypothalamus, it is converted to estradiol (by the enzyme aromatase), and estradiol then facilitates sexual behavior (Nelson, 2011). Consistent with this interpretation, both the enzyme aromatase and estrogen receptors are present in the hypothalamus. Furthermore, the administration of drugs that block the action of aromatase interferes with the behavioral effects of testosterone. Thus we can conclude that the conversion (or “aromatization”) of testosterone to estradiol is necessary for male sexual behavior in rats. So much for the notion that estrogens are “female” hormones.

Testosterone also influences sexual behavior in humans. Most men who have been castrated experience a profound decline in sexual thoughts and sexual behavior. This decline is variable between individuals and can take many months or even years to show itself. Some castrated men continue to experience sexual desires and to have erections in response to erotic visual stimuli, even without any testosterone replacement therapy. In part, this may be because castration does not completely eliminate testosterone and other androgens from the blood: they are still secreted at low levels by the adrenal gland. However, antiandrogen drugs, which should work against androgens of any origin, also have less-than-complete effects in extinguishing sexual desire and behavior (see Chapter 15).

The persistence of sexual thoughts and behavior in some castrated and antiandrogen-treated men suggests that the humans are less enslaved to hormones than are animals like rats. It may be that the relevant mental structures are set up under the influence of sex hormones during development (see Chapter 6), but once established take on a life of their own, reinforcing themselves through a variety of psychological and cultural mechanisms.

There is also some uncertainty about the importance of the aromatization process (the conversion of testosterone to estradiol in the brain) for human sexuality. There have been suggestions that testosterone acts directly on the brain in primates and does not require conversion to estradiol. Aromatization clearly does play some role, however. Aromatase-blocking drugs interfere with sexual activity in male monkeys, and men who are congenitally deficient in the aromatase enzyme have a low sex drive, which can be increased by the administration of estradiol. It seems most likely that the effects of testosterone on men's sexuality are partly direct (via androgen receptors) and partly indirect (via aromatization and estrogen receptors), but the differences between these two kinds of effects remain to be worked out (see Figure 1).

Figure 1  Testosterone acts on the brain through two mechanisms: direct binding to androgen receptors (right), and conversion to estradiol followed by binding to estrogen receptors (left).

References

Nelson, R. J. (2011). An Introduction to Behavioral Endocrinology (4th ed.). Sinauer Associates.

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