|Interstitial nucleus of the anterior hypothalamus|
|Anatomical terms of neuroanatomy|
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 regardless of age and larger in heterosexual males than in homosexual males and heterosexual females. 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 regardless of age.
A study authored by Simon LeVay and published in the journal Science suggests that the region is an important biological substrate with regard 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. Further research has found that the INAH3 is smaller in volume in homosexual men than in heterosexual men because homosexual men have a higher neuronal packing density (the number of neurons per cubic millimeter) in the INAH3 than heterosexual men; there is no difference in the number or cross-sectional area of neurons in the INAH3 of homosexual versus heterosexual men.[note 1] It has also been found that there is no effect of HIV infection on the size of INAH3, that is, HIV infection cannot account for the observed difference in INAH3 volume between homosexual and heterosexual men.
LeVay noted three possibilities that could account for his findings: 1. The structural differences in INAH3 between homosexual and heterosexual males were present prenatally or in early life and aided in establishment of the men’s sexual orientation; 2. The differences appeared postnatally as a result of the men’s sexual feelings or behavior and; 3. Both the differences in INAH3 and sexual orientation are linked to some third confounding variable (such as a developmental event in prenatal or early life). LeVay found the first possibility most probable and noted that the second possibility was unlikely in light of various homologous studies in other species. It has been proven 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 the first possibility. 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 is the homologue of the rat’s SDN-POA.
Other researchers have studied correlations between INAH-3 volume and other aspects of sexual identity. A study of transgender individuals by neuroanatomist Dick Swaab found male-to-female transgender people to have a size and number of neurons of INAH-3 closer to a normal female range, and that female-to-male transgender people 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.
- In their study, Byne et al. found that there was a trend for the INAH3 to be smaller in homosexual men than heterosexual men though the size difference did not quite reach statistical significance by the test that they employed. LeVay notes that Byne et al. used a two-tailed t-test, which is the appropriate test in cases where there is no advance prediction about the direction of a difference. However, LeVay explains that because his 1991 study had determined the INAH3 to be smaller in homosexual versus heterosexual men, using a one-tailed test would have been appropriate. In addition, a one-tailed test would have found a statistically significant difference in INAH3 size between homosexual and heterosexual men.
- Allen LS; Hines M; Shryne JE; Gorski RA (1989). "Two sexually dimorphic cell groups in the human brain". J Neurosci. 9 (2): 497–506. PMID 2918374.
- LeVay, S (Aug 30, 1991). "A difference in hypothalamic structure between heterosexual and homosexual men". Science. 253 (5023): 1034–7. doi:10.1126/science.1887219. PMID 1887219.
- Slimp JC; Hart BL; Goy RW (Feb 17, 1978). "Heterosexual, autosexual and social behavior of adult male rhesus monkeys with medial preoptic-anterior hypothalamic lesions". Brain Res. 142 (1): 105–22. doi:10.1016/0006-8993(78)90180-4. PMID 414825.
- Roselli C; Larkin k; Resko J; Stellflug J; Stormshak F (2004). "Volume of a Sexually Dimorphic Nucleus in the Ovine Medial Preoptic Area/Anterior Hypothalamus Varies with Sexual Partner Preference". Endocrinology. 145 (2): 478–483. doi:10.1210/en.2003-1098. PMID 14525915.
- Balthazart J, Ball G (2007). "Topography in the preoptic region: Differential regulation of appetitive and consummatory male sexual behaviors". Frontiers in Neuroendocrinology. 28 (4): 161–178. doi:10.1016/j.yfrne.2007.05.003. PMC 2100381. PMID 17624413.
- Allen, L.S.; Hines, M.; Shryne, J.E.; Gorski, R.A. (Feb 1989). "Two sexually dimorphic cell groups in the human brain". The Journal of Neuroscience. 9 (2): 497–506. PMID 2918374.
- "Central Nervous System Dimorphisms Related to Reproductive Behaviors" Dale Purves ed., Neuroscience, 2:ed (2001) Online https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.section.2127
- Byne, William; Tobet, Stuart; Mattiace, Linda A.; Lasco, Mitchell S.; Kemether, Eileen; Edgar, Mark A.; Morgello, Susan; Buchsbaum, Monte S.; Jones, Liesl B. (2001-09-01). "The Interstitial Nuclei of the Human Anterior Hypothalamus: An Investigation of Variation with Sex, Sexual Orientation, and HIV Status". Hormones and Behavior. 40 (2): 86–92. doi:10.1006/hbeh.2001.1680. PMID 11534967.
- Simon LeVay (2011). Gay, Straight, and the Reason Why: The Science of Sexual Orientation. Oxford University Press. p. 199. ISBN 978-0-19-973767-3.
- LeVay, S.; Hamer, D.H. (May 1994). "Evidence for a biological influence in male homosexuality". Scientific American. 270 (5): 44–9. doi:10.1038/scientificamerican0594-44. PMID 8197444.
- Gorski, R.A.; Gordon, J.H.; Shryne, J.E.; Southam, A.M. (Jun 16, 1978). "Evidence for a morphological sex difference within the medial preoptic area of the rat brain". Brain Research. 148 (2): 333–46. doi:10.1016/0006-8993(78)90723-0. PMID 656937.
- Döhler, K.D.; Coquelin, A.; Davis, F.; Hines, M.; Shryne, J.E.; Gorski, R.A. (Jun 8, 1984). "Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats". Brain Research. 302 (2): 291–5. doi:10.1016/0006-8993(84)90242-7. PMID 6733514.
- Simon LeVay (2011). Gay, Straight, and the Reason Why: The Science of Sexual Orientation. Oxford University Press. p. 195. ISBN 978-0-19-973767-3.
- Koutcherov, Y.; Paxinos, G.; Mai, J.K. (Jul 20, 2007). "Organization of the human medial preoptic nucleus". The Journal of Comparative Neurology. 503 (3): 392–406. doi:10.1002/cne.21355. PMID 17503490.
- Garcia-Falgueras, A.; Swaab, D.F. (Dec 2008). "A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity". Brain : A Journal of Neurology. 131 (Pt 12): 3132–46. doi:10.1093/brain/awn276. PMID 18980961.
-  Kay Brown (2010), "the Incredible Shrinking Brain"