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===Studies of brain structure=== A number of sections of the [[Human brain|brain]] have been reported to be sexually dimorphic; that is, they vary between men and women. There have also been reports of variations in brain structure corresponding to sexual orientation. In 1990, [[Dick Swaab]] and Michel A. Hofman reported a difference in the size of the [[suprachiasmatic nucleus]] between homosexual and heterosexual men.<ref>{{cite journal | vauthors = Swaab DF, Hofman MA | title = An enlarged suprachiasmatic nucleus in homosexual men | journal = Brain Research | volume = 537 | issue = 1–2 | pages = 141–8 | date = December 1990 | pmid = 2085769 | doi = 10.1016/0006-8993(90)90350-K | url = https://pure.knaw.nl/portal/files/488706/14928_285_swaab.pdf | s2cid = 13403716 }}</ref> In 1992, Allen and Gorski reported a difference related to sexual orientation in the size of the [[anterior commissure]],<ref name="Allen_1992">{{cite journal | vauthors = Allen LS, Gorski RA | title = Sexual orientation and the size of the anterior commissure in the human brain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 15 | pages = 7199–202 | date = August 1992 | pmid = 1496013 | pmc = 49673 | doi = 10.1073/pnas.89.15.7199 | bibcode = 1992PNAS...89.7199A | doi-access = free }}</ref> but this research was refuted by numerous studies, one of which found that the entirety of the variation was caused by a single outlier.<ref>{{cite journal | vauthors = Byne W, Parsons B | title = Human sexual orientation. The biologic theories reappraised | journal = Archives of General Psychiatry | volume = 50 | issue = 3 | pages = 228–39 | date = March 1993 | pmid = 8439245 | doi = 10.1001/archpsyc.1993.01820150078009 }}</ref><ref name="Byne_2001"/><ref>{{cite journal | vauthors = Lasco MS, Jordan TJ, Edgar MA, Petito CK, Byne W | title = A lack of dimorphism of sex or sexual orientation in the human anterior commissure | journal = Brain Research | volume = 936 | issue = 1–2 | pages = 95–8 | date = May 2002 | pmid = 11988236 | doi = 10.1016/s0006-8993(02)02590-8 | s2cid = 7774361 }}</ref> Research on the physiologic differences between male and female brains are based on the idea that people have male or a female brain, and this mirrors the behavioral differences between the two sexes. Some researchers state that solid scientific support for this is lacking. Although consistent differences have been identified, including the size of the brain and of specific brain regions, male and female brains are very similar.<ref name="Cahill_2006">{{cite journal | vauthors = Cahill L | title = Why sex matters for neuroscience | journal = Nature Reviews. Neuroscience | volume = 7 | issue = 6 | pages = 477–84 | date = June 2006 | pmid = 16688123 | doi = 10.1038/nrn1909 | s2cid = 10847255 }}</ref><ref name="Lenroot_2010">{{cite journal | vauthors = Lenroot RK, Giedd JN | title = Sex differences in the adolescent brain | journal = Brain and Cognition | volume = 72 | issue = 1 | pages = 46–55 | date = February 2010 | pmid = 19913969 | pmc = 2818549 | doi = 10.1016/j.bandc.2009.10.008 }}</ref><ref name="McCarthy_2009">{{cite journal | vauthors = McCarthy MM, Wright CL, Schwarz JM | title = New tricks by an old dogma: mechanisms of the Organizational/Activational Hypothesis of steroid-mediated sexual differentiation of brain and behavior | journal = Hormones and Behavior | volume = 55 | issue = 5 | pages = 655–65 | date = May 2009 | pmid = 19682425 | pmc = 2742630 | doi = 10.1016/j.yhbeh.2009.02.012 }}</ref><ref name="Sakuma_2009">{{cite journal | vauthors = Sakuma Y | title = Gonadal steroid action and brain sex differentiation in the rat | journal = Journal of Neuroendocrinology | volume = 21 | issue = 4 | pages = 410–4 | date = March 2009 | pmid = 19226349 | doi = 10.1111/j.1365-2826.2009.01856.x | s2cid = 5558045 }}</ref><ref name="Jäncke_2013">{{cite journal | vauthors = Jäncke L, Mérillat S, Liem F, Hänggi J | title = Brain size, sex, and the aging brain | journal = Human Brain Mapping | volume = 36 | issue = 1 | pages = 150–69 | date = January 2015 | pmid = 25161056 | pmc = 6869393 | doi = 10.1002/hbm.22619 }}</ref><ref name="Berenbaum_2016">{{cite journal | vauthors = Berenbaum SA, Beltz AM | title = How Early Hormones Shape Gender Development | journal = Current Opinion in Behavioral Sciences | volume = 7 | issue = | pages = 53–60 | date = February 2016 | pmid = 26688827 | pmc = 4681519 | doi = 10.1016/j.cobeha.2015.11.011 }}</ref> ====Sexually dimorphic nuclei in the anterior hypothalamus==== LeVay also conducted some of these early researches. He studied four groups of [[neuron]]s in the [[hypothalamus]] called INAH1, INAH2, INAH3 and INAH4. This was a relevant area of the brain to study, because of evidence that it played a role in the regulation of [[sexual behaviour in animals]], and because INAH2 and INAH3 had previously been reported to differ in size between men and women.<ref name="LeVay_1991">{{cite journal | vauthors = LeVay S | title = A difference in hypothalamic structure between heterosexual and homosexual men | journal = Science | volume = 253 | issue = 5023 | pages = 1034–7 | date = August 1991 | pmid = 1887219 | doi = 10.1126/science.1887219 | s2cid = 1674111 | bibcode = 1991Sci...253.1034L }}</ref> He obtained brains from 41 deceased hospital patients. The subjects were classified into three groups. The first group comprised 19 gay men who had died of [[AIDS]]-related illnesses. The second group comprised 16 men whose sexual orientation was unknown, but whom the researchers presumed to be heterosexual. Six of these men had died of AIDS-related illnesses. The third group was of six women whom the researchers presumed to be heterosexual. One of the women had died of an AIDS-related illness.<ref name="LeVay_1991"/> The [[HIV-positive people]] in the presumably heterosexual patient groups were all identified from medical records as either [[intravenous drug abuse]]rs or recipients of [[blood transfusion]]s. Two of the men who identified as heterosexual specifically denied ever engaging in a homosexual sex act. The records of the remaining heterosexual subjects contained no information about their sexual orientation; they were assumed to have been primarily or exclusively heterosexual "on the basis of the numerical preponderance of heterosexual men in the population".<ref name="LeVay_1991"/> LeVay found no evidence for a difference between the groups in the size of INAH1, INAH2 or INAH4. However, the INAH3 group appeared to be twice as big in the heterosexual male group as in the gay male group; the difference was highly significant, and remained significant when only the six AIDS patients were included in the heterosexual group. The size of INAH3 in the homosexual men's brains was comparable to the size of INAH3 in the heterosexual women's brains.{{Citation needed|date=March 2019}} William Byne and colleagues attempted to identify the size differences reported in INAH 1–4 by replicating the experiment using brain sample from other subjects: 14 HIV-positive homosexual males, 34 presumed heterosexual males (10 HIV-positive), and 34 presumed heterosexual females (9 HIV-positive). The researchers found a significant difference in INAH3 size between heterosexual men and heterosexual women. The INAH3 size of the homosexual men was apparently smaller than that of the heterosexual men, and larger than that of the heterosexual women, though neither difference quite reached statistical significance.<ref name="Byne_2001">{{cite journal | vauthors = Byne W, Tobet S, Mattiace LA, Lasco MS, Kemether E, Edgar MA, Morgello S, Buchsbaum MS, Jones LB | display-authors = 6 | title = The interstitial nuclei of the human anterior hypothalamus: an investigation of variation with sex, sexual orientation, and HIV status | journal = Hormones and Behavior | volume = 40 | issue = 2 | pages = 86–92 | date = September 2001 | pmid = 11534967 | doi = 10.1006/hbeh.2001.1680 | s2cid = 3175414 }} {{dead link|date=March 2020 |bot=InternetArchiveBot |fix-attempted=yes}}</ref> Byne and colleagues also weighed and counted numbers of neurons in INAH3 tests not carried out by LeVay. The results for INAH3 weight were similar to those for INAH3 size; that is, the INAH3 weight for the heterosexual male brains was significantly larger than for the heterosexual female brains, while the results for the gay male group were between those of the other two groups but not quite significantly different from either. The neuron count also found a male-female difference in INAH3, but found no trend related to sexual orientation.<ref name="Byne_2001" /> LeVay has said that Byne replicated his work, but that he employed a two-tailed statistical analysis, which is typically reserved for when no previous findings had employed the difference. LeVay has said that "given that my study had already reported a INAH3 to be smaller in gay men, a one tailed approach would have been more appropriate, and it would have yielded a significant difference [between heterosexual and homosexual men]".<ref name="LeVay_2016" />{{rp|110}} [[J. Michael Bailey]] has criticized LeVay's critics—describing the claim that the INAH-3 difference could be attributable to AIDS as "aggravating", since the "INAH-3 did not differ between the brains of straight men who died of AIDS and those who did not have the disease".<ref name="Bailey_2003">{{cite book |url=https://www.researchgate.net/publication/281747420 |title=The Man Who Would Be Queen |vauthors=Bailey J |date=2003-03-10 |publisher=Joseph Henry Press |isbn=978-0-309-08418-5 |format=PDF}}</ref>{{rp|120}} Bailey has further criticized the second objection that was raised, that being gay might have somehow caused the difference in INAH-3, and not vice-versa, saying "the problem with this idea is that the hypothalamus appears to develop early. Not a single expert I have ever asked about LeVay's study thought it was plausible that sexual behavior caused the INAH-3 differences."<ref name="Bailey_2003" />{{rp|120}} The SCN of homosexual males has been demonstrated to be larger (both the volume and the number of neurons are twice as many as in heterosexual males). These areas of the hypothalamus have not yet been explored in homosexual females nor bisexual males nor females. Although the functional implications of such findings still have not been examined in detail, they cast serious doubt over the widely accepted Dörner hypothesis that homosexual males have a "female hypothalamus" and that the key mechanism of differentiating the "male brain from originally female brain" is the epigenetic influence of testosterone during prenatal development.<ref>{{cite journal | vauthors = Swaab DF, Gooren LJ, Hofman MA | title = Gender and sexual orientation in relation to hypothalamic structures | journal = Hormone Research | volume = 38 | issue = Suppl 2 | pages = 51–61 | year = 1992 | pmid = 1292983 | doi = 10.1159/000182597 | doi-broken-date = 1 November 2024 | url = https://pure.knaw.nl/portal/en/publications/gender-and-sexual-orientation-in-relation-to-hypothalamic-structures(7cb8b769-4329-407a-b0ee-13e011017f68).html | hdl-access = free | hdl = 20.500.11755/7cb8b769-4329-407a-b0ee-13e011017f68 | type = Submitted manuscript }}</ref> A 2010 study by Garcia-Falgueras and Swaab stated that "the fetal brain develops during the intrauterine period in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. In this way, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation are programmed or organized into our brain structures when we are still in the womb. There is no indication that social environment after birth has an effect on gender identity or sexual orientation."<ref>{{Citation |last1=Garcia-Falgueras |first1=Alicia |title=Sexual Hormones and the Brain: An Essential Alliance for Sexual Identity and Sexual Orientation |date=2010 |journal=Endocrine Development |volume=17 |pages=22–35 |editor-last=Loche |editor-first=S. |url=https://karger.com/books/book/2680/chapter/5758416 |access-date=2024-06-13 |publisher=S. Karger AG |language=en |doi=10.1159/000262525 |isbn=978-3-8055-9302-1 |last2=Swaab |first2=Dick F. |pmid=19955753 |editor2-last=Cappa |editor2-first=M. |editor3-last=Ghizzoni |editor3-first=L. |editor4-last=Maghnie |editor4-first=M. |url-access=subscription}}</ref> ====Ovine model==== The [[domestic ram]] is used as an experimental model to study early programming of the neural mechanisms which underlie homosexuality, developing from the observation that approximately 8% of domestic rams are sexually attracted to other rams (male-oriented) when compared to the majority of rams which are female-oriented. In many species, a prominent feature of sexual differentiation is the presence of a sexually dimorphic nucleus (SDN) in the preoptic hypothalamus, which is larger in males than in females. Roselli et al. discovered an ovine SDN (oSDN) in the preoptic hypothalamus that is smaller in male-oriented rams than in female-oriented rams, but similar in size to the oSDN of females. Neurons of the oSDN show [[aromatase]] expression which is also smaller in male-oriented rams versus female-oriented rams, suggesting that sexual orientation is neurologically hard-wired and may be influenced by hormones. However, results failed to associate the role of neural aromatase in the sexual differentiation of brain and behavior in the sheep, due to the lack of defeminization of adult sexual partner preference or oSDN volume as a result of aromatase activity in the brain of the fetuses during the critical period. Having said this, it is more likely that oSDN morphology and homosexuality may be programmed through an androgen receptor that does not involve [[aromatisation]]. Most of the data suggests that homosexual rams, like female-oriented rams, are masculinized and defeminized with respect to mounting, receptivity, and gonadotrophin secretion, but are not defeminized for sexual partner preferences, also suggesting that such behaviors may be programmed differently. Although the exact function of the oSDN is not fully known, its volume, length, and cell number seem to correlate with sexual orientation, and a dimorphism in its volume and of cells could bias the processing cues involved in partner selection. More research is needed in order to understand the requirements and timing of the development of the oSDN and how prenatal programming effects the expression of mate choice in adulthood.<ref>{{cite journal | vauthors = Roselli CE, Stormshak F | title = Prenatal programming of sexual partner preference: the ram model | journal = Journal of Neuroendocrinology | volume = 21 | issue = 4 | pages = 359–64 | date = March 2009 | pmid = 19207819 | pmc = 2668810 | doi = 10.1111/j.1365-2826.2009.01828.x | author2-link = F. Stormshak | name-list-style = amp | author-link = C. E. Roselli }}</ref>
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