|Brain: Interstitial nucleus of the anterior hypothalamus|
INAH-3 is the short form for the third interstitial nucleus of the anterior hypothalamus, and is the sexually dimorphic nucleus of humans. The INAH-3 is significantly larger in males than in females irrespective of age. Homologues of the INAH-3 have been observed taking a direct role in sexual behavior in rhesus monkeys, sheep, and rats.
The term INAH (interstitial nuclei of the anterior hypothalamus), first proposed in 1989 by a group of the University of California at Los Angeles, refers to 4 previously undescribed cell groups of the preoptic-anterior hypothalamic area (PO-AHA) of the human brain, which is a structure that influences gonadotropin secretion, maternal behaviour, and sexual behavior in several mammalian species. There are four nuclei in the PO-AHA (INAH1-4). One of these nuclei, INAH-3, was found to be 2.8 times larger in the male brain than in the female brain irrespective of age.
A study authored by Simon LeVay and published in the journal Science suggests that the region is an important biological substrate with regards to sexual orientation. This article reported the INAH-3 to be smaller on average in homosexual men than in heterosexual men, and in fact has approximately the same size in homosexual men as in heterosexual women. This study was criticized as having various methodological flaws, including the use of brain samples from patients who had died from AIDS.
LeVay's study could be interpreted as suggesting that the region could have a biological substrate in sexual orientation, but that alone does not signify that the size of INAH-3 as a sole cause or consequence of an individual's sexual orientation. For instance, LeVay himself cited possibilities that could account for this phenomenon, including changes in hormonal exposure or sensitivity during early development, or that the brain region changed in response to the behavior and was not the cause of it, or that there exists some unidentified confound which both changes the anatomy of the brain and influences sexual behavior, meaning the correlation seen in the INAH-3 is not causal. However, it was proved that in rats, the sexually dimorphic nucleus of the preoptic area (SDN-POA) appears during the perinatal sensitive period as a consequence of the dependence of its constituent neurons on circulating androgen, thus offering indirect support for hormonal hypothesis. After this period, even extreme interventions, such as castration, have little effect on the size of the nucleus, which would help contradict the second possibility of behavior changing brain structure. It has been suggested that the human INAH-3 was the homologue of the rat’s central nucleus of the medial preoptic area.
Other researchers have studied correlations between INAH-3 volume and other aspects of sexual identity. A study of transsexual individuals by neuroanatomist Dick Swaab found male-to-female transsexuals to have a size and number of neurons of INAH-3 closer to a normal female range, and that female-to-male transsexuals have a size and number of INAH-3 neurons closer to a normal male range. This finding that the size of the INAH-3 more closely corresponded to the gender the subject identified with rather than their biological or chromosomal gender has since been repeated, but is still controversial due to potential confounds of hormone replacement therapy.
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