“At early stages of fetal development the embryo is capable of becoming either a male or a female.” What hormones determine the sexual characteristics of males and females during development?
In the early stages of development both males and females have Mullerian ducts, wolffian ducts and gonads. Before the 6th week, both males and females have a non-developed genital tubercle, urethral fold, urethral groove, genital fold, and anal pit. The Y chromosome has the SRY gene which is responsible for sex determination; it causes the gonads to differentiate into testes. The androgens produced by the testes act as a positive feedback loop by further contributing to male characteristic by producing more androgens as the testes get bigger. Testicular feminization syndrome is the result of having androgen insensitivity or an issue with the androgen receptors. Essentially, an individual that would have otherwise developed into a male, developed into a female because of insensitivity to the androgen hormone. The testicles formed where the ovaries would have formed but the release of androgen didn’t cause the common male characteristics that usually form when there is no androgen insensitivity. In such cases the uterus does not develop but for all intents and purposes the individual is considered a female who isn’t capable of reproduction. The interesting part is that they produce adequate amounts of testosterone from the internalized testicles, it just doesn’t affect the body.
What are the effects of excessive testosterone on a female during early fetal development?
Melissa Hines (2020) goes into great depth when discussing sex-related differences present in females based on prenatal testosterone exposure. For obvious reasons, we can’t simply inject pregnant women with excess testosterone to see what happens. We can, however, test present testosterone (androgen) levels and the resulting effects; Moreover, as we do in many cases, we test on rodents or other animal species. A (1959) study found that substantial testosterone exposure in guinea pigs pregnant with female offspring had long lasting effects associated with sex-differences and sex-related behavior of the female babies (Phoenix et al.,1959). Many studies, in many different species, indicated similar sex-related behavioral changes in female offspring. It should be noted that there is a sensitive period when these effects take place; if you inject an adult female human (results vary depending on species) with testosterone for a short period of time you’ll see little affect. If a female is subject to exposure during this sensitive period, you’ll see organizational effects. Organizational effects are defined as enduring structural effects. Essentially, if a female is exposed during this sensitive period, she will show certain masculine traits/characteristics and certain feminine traits will be suppressed. A study associated with play style and toy choice, done with monkey subjects, showed that prenatal exposure to testosterone to female monkey fetuses increased masculine type play in female offspring. Other differences include aggression and physical activity. Socialization and social expectations play a large role on play style and choice in which toys to play with. The structural differences in males and females refer to the brain—the hypothalamus, the amygdala and the spinal cord. The clitoris will grow larger and rather than arching her back she will thrust as a male would (mounting another female). Research continued to identify sex differences in rodent brain structures based an exposure to testosterone during development. In rats, in the pre-optic area, the females had more non-amygdaloid synapses on the dendritic spines. Treating the females with testosterone during early developmental stages decreased number of dendritic spines and, inversely, castrating the males increased them. Thus far I have talked about rats and Guinea pigs but substantial differences have also been found in canaries, sheep, and zebra finches. Interestingly in bird species where males sing and females do not, differences were apparent. Hormones associated with the pre-optic area were identifies as having a key role in many sex-related differences. Other brain areas affected include the postero-dorsal area of the amygdala, the encapsulated and medial anterior regions of the bed nucleus of the stria terminalis, and specific areas of the pre-optic area (anteroventral and parastriatal regions). Rams who have larger volume of sexually dimorphic nucleus-preoptic area (SDN-POA) have been found to prefer female partners but rams with lower volume often prefer male partners (Commins & Yahr, 1984; Hines et al., 1985; Tobet et al., 1986; Byne,1998; Roselli et al., 2004; Murakami & Arai, 1989; as cited in, Hines, 2020). Human autopsy studies indicate some sex-related differentiation in the brain similar to the aforementioned differences found in other species. Some differences are correlated with gender identity and sexual orientation.
There are several brain structures that differentiate in males and females. What are these and how do they differ?
Between male and female brain structure, differences are notable; particularly in the hypothalamus but also the pituitary gland, the spinal cord and some other regions of the brain. While the hypothalamus is not the only area that exhibits structural differentiation between males and females, it is relatively well known and understood compared to other differences. The medial pre-optic area has less dendritic spines and synapses in females, the arcuate nucleus and anteroventral periventricular nucleus have more dendritic spines in females, and in the ventromedial nucleus of males the dendritic branches are more widely branching. The hypothalamus in females is responsible for generating a monthly, hormonal, pattern or menstrual cycle. Research in rats shows high levels of alpha-fetoprotein that inhibits estradiol from entering cells in females. In males, testosterone can freely enter the brain, and the hypothalamus in particular, where it is converted to estradiol and has a masculinizing effect. In the medial POA estradiol and testosterone both create prostaglandin E2 which causes increase in dendritic spines and synapses due to increase in microglia. Estradiol activates an enzyme (P13 Kinase) in the ventromedial hypothalamus, presynaptic neurons increase release of glutamate which is what causes postsynaptic dendritic branching to widen. The ventromedial hypothalamus and amygdala also contribute to sexual dimorphism in feeding and reproductive behavior, and aggression. Estradiol increases GABA production in the arcuate nucleus (which we know is important for feeding) and the anteroventral periventricular nucleus. GABA is one of the primary inhibitory neurotransmitters that contributes to relaxation and stress reduction. In this case the GABA production acts on astrocytes to decrease dendritic spines. Males experience a decrease in these areas that are important for female reproductive behavior. The areas do not shrink in females, remaining larger, because of the low levels of estradiol early in development. While the hypothalamus has noteworthy sex-related differences, there are many other regions that differ based on gender. The orbitofrontal cortex, including the ventromedial prefrontal cortex, is larger in women on average. Due to females having larger orbitofrontal cortex and limbic region, a 2009 study suggests emotional intelligence, or emotional reasoning is one psychological difference based on structural gender difference. Also, men have a larger amount of grey matter while women have a larger amount of white matter. Moreover, males have a larger amygdala which plays a large role in male sexuality and also aggression. Beyond that men also have a larger parietal cortex which is associated with spacial perception (Kalat, 2019). There is also some structural differentiation based on sexual orientation. So, in cases where gender would normally differentiate a brain structure, sexual orientation may complicate this. In some cases, the left and right hemispheres of the cerebral cortex are nearly equal size in heterosexual females, but the right hemisphere is a bit larger in heterosexual males. Homosexual males are structurally similar to heterosexual females in resemblance and homosexual females are between heterosexual females and males in resemblance. In heterosexual females, the left amygdala has more widespread connections than the right amygdala. Homosexual males resemble heterosexual females, and homosexual females are structurally intermediate. The anterior commissure is sometimes larger in heterosexual woman than in heterosexual males; in homosexual males, it is at least as large as in women. The SCN is also larger in homosexual than in heterosexual males. We do not know if the aforementioned structural differences are causes or effects, as in many cases, we must acknowledge limitations and avoid speculation when we interpret these findings. Predisposition to particular behaviors may be due to neurobiological differences– but behaviors can change brain anatomy.
What are vasopressin and oxytocin? What appears to be their role in human sexual behavior?
We previously discussed organizational effects on neuroanatomy and sexual behavior, but we must also consider activating effects of sexual hormones. Activating effects can take place at any time, not only during the sensitive periods of development. Levels of estradiol and testosterone can affect behavior at any time and play a role in reproductive, sexual, behaviors and the initiation and inhibition throughout lifespan. Oxytocin is often referred to as the love/bonding hormone because of the large role it plays in bonding and reproductive behaviors; it also has physiological effects, causing uterine contractions and lactation during pregnancy. Sexual pleasure and orgasm release oxytocin which contribute to bonding. Release of oxytocin generally produces a feeling of calmness and decreases anxiety; it also contributes to the pleasure associated with orgasm which has a positive effect on reproduction and sexual behavior, having a facilitatory effect. Dopamine is essential in motivation and reward pathways and it plays a role in male sexual motivation and arousal. Vasopressin is a hormone or more specifically a neuropeptide that contributes to many internal regulatory mechanisms—it performs a neuro-modulatory role in the nervous system of both genders. In males, vasopressin release contributes greatly to parenting and bonding. As Robert Sapolsky would say, “vasopressin is to males as oxytocin is to females”. To elaborate, vasopressin in males is correlated with pair bonding and parenting. In monogamous species you will find expression of the vasopressin receptor gene on neurons that release dopamine. Studies have shown, in voles, that males with more of these receptors on the dopamine neurons bond with their mates and further, voles with more receptors form bonds faster—in other words they mate fewer times in general before forming a bond with a female vole.
Enlightening research by LeVay Actions and Zhou Actions regarding structural difference based on sexual orientation or transsexual differences:
Describe the research comparing brain structures of transsexual males. What evidence is presented for anatomical differences? Which brain structures are implicated and how.
For obvious reasons, often times studying a relevant nonhuman population is preferential or at lease very helpful, due to ethical concerns and other difficulties in studying the human population. There are clear limitations in using a nonhuman population to study sexual identity; However, we are less limited than it may seem. Research of the bed nucleus of the stria terminalis (BST) of nonhuman population has contributed to our understanding sexual identity in valuable ways. The BST is important to our understanding of animal sexual behavior. Sex-related hormone receptors are present in this area along with connections between the amygdala and bed nucleus of the stria terminalis that contribute to sexual dimorphic behaviors. Steroids associated with the gonads influence the size of the BST during sensitive developmental periods. In humans a particular region of the BST has been denoted as being larger in males than females and is independent of sexual orientation. The Zhou study indicates that the BST in male-to-female transexuals is smaller. That information, along with nonhuman studies, leads researchers to posit that gender identity is established during sensitive developmental stages associated with differing sexual organization. The fact that removal of the androgen producing gonads neonatally causes significant changes in BST size and inhibits the sexual dimorphism, aligns with this hypothesis.
Research comparing heterosexual and homosexual male anatomy. What evidence do they present for anatomical differences? How do these brain structures differ.
Of the 4 cell groups of the interstitial nuclei of the anterior hypothalamus, the 3rd group ( in the pre-optic-anterior hypothalamic area—or PO-AHA), is referred to as being responsible for sexual dimorphism in reference to sexual orientation. INAH-3 is generally found to be larger in the male brain than the female brain; however, this study indicates the region is smaller, in general, in homosexual males than in heterosexual males. The INAH-3 cell group in homosexual men resembles that of a heterosexual woman. The structural differences could have been present prenatally, during the sensitive period of development, and affected later sexual orientation; The differences could be linked by a confounding unknown variable; Or, the differences could have been the result of sexual orientation/feelings. It would be speculation to associate cause and effect; as previously mentioned, in rodent studies it has been shown that the sexually dimorphic nucleus of the pre-optic area appears during the sensitive developmental period as a result of present hormones. If we associate the SDN-POA of rodents with the INAH-3 of humans, we can posit that the structural changes could have occurred during the sensitive period and contributed to the sexual orientation of the homosexual individuals. Furthermore, in the rodent population, after the changes in the SDN-POA had taken place, even castration didn’t have a significant effect on the size; contributing to the idea that the structural changes were not a result of the behavior. The LeVay study was widely publicized and also championed in the gay community. One reason may be because LeVay was openly gay; in fact memorabilia marketed to the gay community not long after this study included shirts that said “the only thing small about me is my SDN”, apparently INAH-3 hadn’t caught on and sexually dimorphic nuclei was the preferred terminology in that case!
Thought question: How might an understanding of the biology of sexual orientation enter into debate regarding LGBT rights?
Up until a certain point, being homosexual was actually recognized as a mental illness in the diagnostic and statistical manual (DSM). Over time society has become more open to differences in sexual orientation and gay rights have spread more widely. Scientific advances have the potential to dispute myths such as “being gay is a choice”. Historically there have been places homosexuals went to get treatment in hopes of changing their sexual orientation—sometimes of their own volition because they were unhappy and more often through encouragement to change or persecution for living in such a way. Understanding the biological bases for these physiological differences in people spurred a different outlook and a fuller understanding of what is happening internally; which can be good, but it can also be damaging, depending on how it is used. A study was done before LeVay’s research, that also showed structural differences in the brain, but the study was taken in a completely different way. It was taken poorly by the gay community, as an affront or attempt to find something wrong with them; when the LeVay study found differences, it was celebrated by the gay community. I will speculate that the fact that LeVay was openly gay played a role there. Scientific data can be manipulated into an argument for either side in such cases. A favorable argument for LGBTQ+ rights is that the structural differences are comparable to that of a women, linking sexual orientation to a region of the brain—if women are considered to have healthy brains then it would be tough to argue that it is only unhealthy if part of the male brain is similar to that of a women. Our species doesn’t depend on procreation at this point so there are few arguments against LGBTQ+ rights that hold credence. Because we now have a clearer view on structural differences, treatment could be offered/designed and encouraged based on new scientific advances, further dividing the opposing sides. I think those with a moderate view or who misunderstand the situation may be quite enlightened by the information; those who are anti-LGBTQ+ rights will probably use the structural differences as fuel; and LGBTQ+ can take it as good, bad, or neutral depending on how they feel the knowledge will affect them as people.
Hines, Melissa. “Neuroscience and Sex/Gender: Looking Back and Forward.” The Journal of Neuroscience, vol. 40, no. 1, 2019, pp. 37–43., doi:10.1523/jneurosci.0750-19.2019.
Kalat, J. W. (2019). Biological psychology (13th ed). Boston, MA: Cengage.
Other resources: Stanford open-course lectures by Robert Sapolsky.
Reblogged this on My Aria.