Friday, May 24, 2013

At Least Four Sexes

At Least Four Sexes

Affective Neuroscience: The Foundations of Human and Animal Emotions. Jaak Panksepp. pp 231-234.

Genetic Sex and Fetal Sexual Differentiation

The ever-increasing appreciation of the differences between the organizational and activational compo­nents of sexuality has deepened our understanding of what it means to be male or female. A photographic analogy helps us envision these distinct processes. The hormonal patterns that are set in place during the organizational phase of fetal development help "expose" the imprint of maleness or femaleness on maturing brain circuits, as well as on bodily appearance. The hormones secreted at the onset of puberty eventually "develop'' the exposed "negative,'' thereby activating the latent male or female sexual proclivities that have remained comparatively dormant within brain circuits since infancy. If brain and body organization do not match up, the individual will have to discover, through painful experience, which gender was predominantly imprinted within his or her brain, and to what extent. This can be a stressful and lonely psychological journey.

Animal research has indicated that the male and female poles of brain sexuality reflect extremes of a gradient that allows for many intermediary types. Although male and female sexuality are distinct to a substantial extent, each sex does in fact possess circuits for both forms of behavior, but typically to different degrees. The fact that male and female brains have distinct but related psychosocial proclivities allows sexual urges to become quite complicated in the real world. The possible permutations allow for cross-sexual variants that society is still trying to reconcile with long-standing cultural expectations, which are sometimes based on ignorance and intolerance. This issue was poignantly highlighted when President Clinton attempted to open the doors of the military to homosexuals at the start of his presidency in 1993, but the forces of ignorance and discrimination prevailed. Brain scientists have suspected for many decades that there are intrinsic brain organizational patterns that promote certain forms of homosexuality. The remarkable confirmatory story that has now been worked out in animal models is only slowly percolating into our general cultural imagination. To highlight this story for my students, I typically ask them a seemingly inane question: "How many genders or sexes are there?" At first they look puzzled, but courageous students are willing to provide the reasonable and expected answer: "two." I tell them how curious it is that our modern society still holds on to such prescientific views, for "four or more" is certainly a more accurate answer. Indeed, this is the belief some Native American tribes held as the correct description of their social world. They believed that in addition to the prevailing variants of man within man and woman within woman, nature sometimes created a man’s mind within the body of a woman and a woman's mind within the body of a man. The essential accuracy of this view has now been affirmed by years of scientific research on the development and expression of sex circuits inside the rodent brain. Indeed, one could argue that there can be an "infi­nite number'' of permutations along the biochemically determined gradients of brain and body masculinization and feminization. However, for our purposes "four'' is certainly a more accurate answer than "two" as an estimate of the major types of gender (brain/mind ) and sex (body) identities that actually exist in the world . Although the details have been worked out in lower animals, existing evidence suggests that similar principles also operate in humans.

In simplest terms, the brain organizational story goes like this. One is typically born either genetically female (with the XX pattern of sex chromosomes) or genetically male (with the XY pattern). What the Y chromosome provides for the male is testis determining factor (TDF), which ultimately induces the male gonadal system to manufacture testosterone. The XX pattern allows things to progress in the ongoing feminine manner, unless some external source of testosterone (or, more accurately, one of its metabolites) intervenes. The actual manner in which male brain and body development proceeds is determined by the timing and intensity of the resulting hormonal organizational signals, namely, testosterone and two closely related metabolic products, estrogen and dihydrotestosterone (DHT). These last two steroid hormones normally control the final trajectory of brain and body development, respectively, while the XY baby is still in the womb-still hidden from the cultural influences of its future social world (Figure 12.3).

These hormones can similarly affect female devel­opment if they happen to be present in sufficiently high levels during pregnancy. However, the XX sex chromosome pattern informs the female body to manufacture proteins such as the steroid-binding factor alpha-fetoprotein, which can thwart the cross-gender organizational influences of sex steroids during early development. This protects the female fetus from being masculinized by the generally high levels of maternal estrogens. If there is not enough of this fail-safe factor, or if the maternal levels of estrogens are so high that they saturate the available alpha-fetoprotein, the female will proceed toward a male pattern of development-sometimes in both body and mind, sometimes in one but not the other, depending on the hormonal details that have transpired.

The four major types of organizational permutations can yield the obvious forms of cross-sexual gender iden­tities: the presence of male like brains in female bodies and of female brains in male like bodies. The fact that individuals who look like men on the outside can come to feel like women on the inside, and individuals who look like women on the outside can come to feel like men on the inside, arises from a simple biological fact. The signals that trigger babies’ brains and bodies to take the various possible gender and sex paths are separate (Figure 12.3). Initially, all fetuses are female like, and masculinity emerges from distinct prenatal signals that tell the brain and body to be masculinized. After the TDF gene has induced the male fetus to manufacture testosterone, several critical events must take place before the male brain and body phenotypes can be fully expressed (Figure 12.3). First, testosterone needs to be converted in two distinct one-step reactions to estrogen and DHT. The final organizational signal that tells the brain to masculinize is estrogen, and the signal that tells the body to develop along male-typical lines is DHT. Of course, these sexual potentials, laid down in the brain and body during gestation and infancy, do not become fully manifested until puberty.

With our current understanding of this organizational phase of psychosexual development, it is no longer a surprise that estrogen, a steroid hormone that is associated with female sexuality in the popular imagination, helps organize the intrinsic brain aspects of male gender identity in many species. To understand this, we need to consider the metabolism of testosterone (Fig­ure 12.3). After testosterone has been synthesized from cholesterol, via many steps that include the interme­diates progesterone and dehydroepiandrosterone, it can be biochemically modified in two distinct ways. Along one metabolic path, it can be converted into DHT with the assistance of the enzyme 5-α-reductase. Along the other path, it can be converted into estrogen by the enzyme aromatase. These products of testosterone metabolism are critical ingredients that dictate whether a genetic male will continue along the male path in terms of body and brain development, both before and after puberty. Various forms of homosexuality and bisexuality are promoted if '"errors” occur in the various control points of these biochemical processes-if the developing male brain is not bathed in testosterone at the sensitive time or if it is missing the enzyme aromatase that converts testosterone to estrogen.

Figure 12.3. Both the brain and body of mammals are initially organized according to a female characteristic plan. Maleness emerges from two distinct influences of testosterone on body tissues-masculinization of the brain being mediated by estrogen (E) and of the body by dihydrotestosterone (DHT). Different tissues can convert testosterone to different products because of the enzymes they contain. DHT is manufactured in cells containing 5-α-reductase, and E is manufactured in those that contain aromatase.

If the female brain is exposed to too much estrogen during the sensitive periods of development (the precise time varies from species to species), it will assume male like characteristics while leaving the body feminine. Females such as these will preferentially exhibit male-typical behaviors at maturity, but only if their brains are exposed to the activational effects of testosterone at that time. Indeed, in humans, tomboyishness in females has been promoted by maternal injections of diethylstilbestrol ( DES), an estrogenic hormone that was given to pregnant mothers during the second trimester to prevent miscarriages in the 1940s and 1950s.

Conversely, in the absence of fetal estrogen but with sufficient DHT, a male body can emerge with female­ type circuits hidden within the brain. A naturally occurring instance of this type of organizational development has been found in a small group of individuals in the Dominican Republic. These boys, called guevedoces, which literally means “penis at 12," are genetically deficient in 5-α-reductase. They have a female appearance at birth, with some enlargement of the clitoris and no apparent testicles (which are present but remain undescended within the body). However, their fetal gonads do apparently secrete testosterone at the usual time, and since they have normal aromatase activity, it is convened to estrogen but not DHT. Accordingly, their brains, but not their bodies, are fully organized along male lines. When such boys enter puberty and begin to secrete testosterone, they develop male-typical bodies-with an increase of body hair, deepening of the voice, enlargement of the penis, and, finally, the descent of the testes. Male-typical sexualurges also begin to emerge. Thus, the boys’ pubescent erotic desires come to be directed toward females, even though they were reared as girls throughout childhood. This probably indicates that the male brain is instinctively prepared to respond to certain features of human femaleness, including racial and bodily characteristics, voice intonations, as well as ways of being.

There are yet other fascinating variants of psycho­sexual expression in humans that are probably biologically based but less well understood. For instance, some males have an extra female chromosome (i.e., XXY) and exhibit Klinefelter's syndrome, which is character­ized by exceptionally small gonads. Such children are often temperamentally passive, socially dependent, and mentally slow. On the other hand, boys with an extra male chromosome (i.e., XYY) have been claimed to be more hostile and aggressive than normal males, even though these findings are debatable. In addition, many drugs can modify the normal progression of the underlying psychosexual organizational processes, which should caution women against taking any drugs or being exposed to environmental toxins during pregnancy.

These fascinating details of early development inform us of a profound fact of nature: Although male and female are the most typical biologically ordained poles of sexual identity, a vast number of gradations can be produced by normally occurring variations in the underlying hormonal control mechanisms that guide gender differentiation. Because of this, the biological forms of homosexuality do not represent psychological perversity resulting from aberrant psychosocial experiences but simply represent natural variants that can occur in the course of development. Of course, this does not exclude the possibility that humans sometimes voluntarily select gender roles in accord with their whimsical or neurotic cognitive desires. It is possible for someone to be halfway on the biological gradient of masculinity-femininity, and we might expect such individuals to be highly bisexual, with a maximal choice as to which direction they wish to orient their erotic tendencies. Since the real causes arc typically hidden in the brain, it will be difficult to distinguish who is who, and it should not mauer. Obviously, one's erotic choices should remain an individual matter, as long as no coercion or child abuse is involved.

In sum, the major role of sex chromosomes is to dictate which enzymes and hormones will be manufactured by the developing reproductive apparatus. The XY chromosome pattern tells the male's body to manufacture testosterone at critical periods of development, setting in motion a cascade of changes in the prototypical female-type brain. This type of brain masculinization can also occur in females, which can promote cross­ sexual behavioral and erotic tendencies in adulthood. The traditional XX pattern of femaleness will emerge, even in genetic males, if such early hormone secretions do not occur. Thus, the brain substrates for sexuality that are organized by these early hormonal experiences help determine what type of gender identity, erotic desires, and sex behaviors individuals will exhibit at puberty, when the elevations in hypothalamic gonadotrophic hormones and gonadal sex steroids begin to "activate" sexual tendencies (Figure 12.4).

Although the exact details or the hormonal cascades controlling these early organizational events vary somewhat among species, they are sufficiently similar in rats and humans that work on the former has elucidated the patterns that were subsequently found in the inner. But there presumably are differences in the magnitude of the cross-gender effects that can be achieved in different species. For instance, existing evidence suggests that rats exhibit larger brain changes during fetal masculinization than do humans, which would be in line with the larger average differences in body size between males and females. Usually the average gender difference in body size is considered an index of the extremity of sex roles in a species. Thus, it is to be expected that "tournament species" such as elk and walruses, in which intermale competition and the seeking of dominion over females are extreme, will exhibit the largest dimorphism between the sexes. In comparison with such creatures, the relative biologically based gender differences are modest in humans. On the other hand, in such species as the spotted hyena, we would predict the tables would be turned, but sufficient brain data have not yet been collected.

For a summary of The MATING System, the Brain, and Gender Determination parts of Pankseep’s book by Sara-Neena Koch see

1 comment:

  1. This evidence gives hope that the preoccupation of religion and politics about "sexual behavior" may be mitigated by a better-developed scientific understanding of "gender." :-)