The basic human prototype is, in one respect, female

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The larger a chromosome is,  the more important is its role in maintaining life.  The X chromosome is in fact a rather large chromosome which functions essentially as does a medium-sized autosome.  In sheer size it comes closest to the eleventh chromosome,  which by definition is the eleventh largest.  It programs the creation of a diversity of amino acids, proteins, enzymes and so forth. It is really just the tiny Y chromosome which determines the sex of the progeny, namely maleness.  Why is this so ?   In fact,  biologically speaking the male can be considered a slight complication of the basic biological prototype of the human species,  which is female.   A person who is born the victim of a chromosomal aberration such as having only one X chromosome, ought, arithmetically, to look half male and half female.   Recall that the father carries an X and a Y chromosome,  and the mother carries two X chromosomes.   However,  the person born with only an X chromosome, although very androgynous, looks more like a female.  As we shall see in detail later, this condition is called Turner's syndrome. A person who, for any number of reasons, has an interruption of the developmental cascade leading to the male phenotype,  will essentially look like a female.   Humans do not need chromosomes or gonads or sex-specific hormones to look female.   But they do need all of these things to look male.  

It is of note that the chain of transformation (synthesis) of molecules from sterol to testosterone (the male hormone) involves an intermediary step which is estrogen (the female hormone). Both estradiol and testosterone (as well as the other steroids) are highly  lipophilic (fat solubile) and thus easily pass through the lipid bilayer of cells. Thus intracellular concentrations of steroids are related to actual circulating levels.  What determines whether a cell responds to a steroid is either what sorts of cell-surface receptors it has (so-called nongenomic effects of steroids and maybe better termed cell-surface effects) and what sort of intracellular receptors it has.  A great many cells clearly have intracellular androgen receptors, thus there are many actions of androgen where it is acting as an androgen and not as estrogen.  Many many cells have estrogen receptors as well as the enzymes to convert some androgens to estrogens.  It is within these cells that testosterone (or any other aromatizable androgen) can enter the cell, be converted to estrogen, and then activate estrogen receptors. But only a very small percentage (<1%) of testosterone is ever converted to estrogen in the mammalian brain. Nevertheless that small percentage does have behavioral effects in rats and ferrets.  There is not yet any evidence of this eventuality in humans.   Testosterone ( androgen) is present in the blood plasma in bound (approximately 96%) and unbound, free (approximately 4%) forms.  It is the free form which is lipophilic (water soluble) and can easily pass across cell membranes  into the cell cytoplasm where it is bound to the androgen receptor .  This is the reason there is the condition known as « androgen insensitivity »  -because people with this condition do not have enough of the receptor or it is an abnormal form. In a normal male mammal, the hormone receptor complex enters the nucleus where it activates protein synthesis of "male" proteins,  etc.  At one time it was thought, by some, that androgens could only penetrate brain cells by first being converted to estrogens.  This, however, is now known not to be so.

Sexual behavior of sheep can be radically reversed by prenatal hormonal manipulation.  A single injection of testosterone into the pregnant ewe,  after her progeny has aleady been morphologically fully feminized,  may nevertheless fully masculinize the progeny’s sexual behavior.  Upon arrival of the first sexual action,  the female progeny behaves exactly like a ram and not at all like an ewe.  Sheep sex is hormonally robotic in this respect.   This is not the case for humans.  The brain metabolism of sex hormones is complex and remains mysterious.

Fetuses exposed to excessive doses of estrogen may, at certain doses, in fact be masculinized,  not only in body appearance but also in psychological make-up  -but these effects depend on the tissues under consideration, the timing of the dose, and on the species under consideration.   For example, estrogen, derived from circulating testosterone, masculinizes the developing preoptic area of the brain in some species. This nucleus is  one of the most sexually dimorphic brain nuclei.   It is important to understand that artificial or abnormal prenatal hormonal effects may produce distinct effects:  masculinization, demasculinization, feminization, or defeminization.   It is not easy to be sure which of these is taking place in artificial or abnormal prenatal hormonal conditions.  It is believed that in normal development of a male rat’s brain,  the animal is masculinized first (prenatally) and defeminized later (postnatally).  It is believed that this is so because the brain only develops receptors specific to estrogen around the time of birth and not before.  In mammals,  it is believed that it is harder to masculinize a female because very early on in prenatal development she secretes a molecule in her blood,  alpha-feto-protein,  which prevents testosterone from masculinizing her.  This innocuous little piece of neuroendocrinology could help explain some remarkable sex differences which are still leaving psychologists puzzled:  for example, why are there so many more diverse paraphylias in the male sex than in the female sex in humans  (see chapter 2),  and why are sexual identity and sexual orientation very much more fragile in the male sex than in the female sex in humans (see chapter 6) ?   However, even though brain development makes mysterious use of sex hormones,  we must not lose sight of the bigger picture:  normal young women have about three to five times more estrogen circulating in their blood than normal young men do,  making estrogen, clearly, a «female» hormone.