As you go through this review, keep in mind that:

During development it is the absence of testosterone (and not the presence of estrogen or any other substance) that feminizes females. Also keep in mind that the only way you can prevent a male from developing male structures is to deprive him of testosterone or its effects. Giving him estrogen will not make him female.

Sexual differentiation is an example of how hormones can play an organizational (rather than activating) effect. Activating effects of hormones concern their influence on behavior, not structure, and include hormonal control of sexual and parental behaviors (for example).

SEXUAL DIFFERENTIATION OF THE MAMMALIAN BODY

Step 1 = Gonadal Development (gonadal sex)

All fetal mammals, regardless of whether they are XX or XY (their genetic sex) start out with the same primordial gonads. These gonads have the potential to become either testes or ovaries. To become testes, H-Y antigen must be present. H-Y antigen is present if the fetus has a Y chromosome. For genetically male fetuses, the Y chromosome contains a gene that codes for the protein called H-Y antigen, and this protein gets secreted very early on in development. When H-Y antigen secretion begins, the primordial gonads become testes. If there is no Y chromosome (thus, the fetus is a genetic female) then there is no H-Y antigen. In the absence of H-Y antigen, the primordial gonads become ovaries.

Step 2 = Duct Development (morphological sex)

Now the fetus has to develop the appropriate set of internal structures. Every fetus, male or female, begins life with 2 separate systems that could eventually become internal reproductive organs. Those 2 systems are the Wolffian system, and the Mullerian system. If the fetus is XY, and has secreted H-Y antigen and therefore developed testes, those testes start functioning and secreting testosterone. In the presence of testosterone, the Wolffian system becomes the vas deferens and seminal vesicles. Also, if the fetus is XY, the testes secrete Mullerian inhibiting substance, which causes the Mullerian system to degenerate. If the fetus is XX, it has no testosterone and has no Mullerian inhibiting substance. In the absence of testosterone, the Wolffian system will not develop. In the absence of Mullerian inhibiting substance, the Mullerian system does develop, and becomes a uterus and Fallopian tubes and vagina.

Step 3 = Genital Development (physiological sex)

Now all that's left to do is form the appropriate external genitalia. All fetuses, male and female, start out with the same primitive external genital structure (check out the picture in your book in Chapter 11). If the fetus is XY, the presence of testosterone will cause that primitive structure to become a penis and scrotum. If the fetus is XX, the absence of testosterone will cause that primitive structure to develop into a clitoris, labia, and vaginal opening.

SEXUAL DIFFERENTIATION OF THE BRAIN Now its time for a bit of a switch. Sexual differentiation of the body is dependent on the presence or absence of testosterone. But sexual differentiation of the mammalian brain is dependent on the presence or absence of estradiol, which is formed from testosterone. So, if a fetus is XY, and is secreting testosterone, some of that testosterone is getting converted to estradiol, crossing the blood brain barrier (BBB) into the male fetus' brain, and masculinizing it. "Masculinizing" it means giving it characteristics of a male brain, like being bigger, having a different metabolic pattern, and some larger structures (INAH-3, SDN-POA) compared with female brains. If the fetus is XX, there is no testosterone to be converted to estradiol. There is, however, circulating estradiol in the mother's bloodstream. To prevent the brains of female fetuses from being masculinized by their mother's estradiol, female fetuses have alpha-fetoprotein. Alpha-fetoprotein binds to estradiol and disables it, so it can't get into the female's brain and masculinize it. Male fetuses have alpha-fetoprotein too, but it can't cross the BBB. Testosterone can cross the BBB, and it does, and is converted to estradiol in the brain of a male fetus, where alpha-fetoprotein can't disable it.