Sexual Orientation

1. Sexual Orientation Kristin Happ May 2, 2005

2. Let’s cover the basics… • Sexual Orientation – feeling attracted toward a particular gender • Basic groups: • Heterosexuals • Homosexuals • Bisexuals • Asexuals • Sexual Identity – being physically or genetically masculine or feminine • Gender Identity – feelings of being either masculine or feminine • Transgendered ≠ Cross-dressing

3. What typically happens? • Animal data shows us that steroid exposure during the neonatal period influences the organization of the brain and influences sexual behavior and preferences • We learned in Dr. Mong’s lecture about what happens to induce heterosexual behavior. • Males – need testosterone aromatized to estradiol to perform, importance of the POA • Females – in animals, reproductive behaviors tightly linked to estrous cycle, OT regulates lordosis, importance of the VMN

4. So why isn’t everyone heterosexual? • Hormones? Yes • Genetics? Maybe • Developmental factors? Yes • Social factors? No

5. Early Androgen Exposure Many studies have been done on the effects of possible early androgen exposure for both males and females. Exposure during the 2nd trimester increases cerebral asymmetry via accelerated growth of the right hemisphere There is a higher frequency of non-right-handedness in both homosexual men and women. Greene, 2002

6. Bone Growth Androgen and estrogen exposure control sexual dimorphism in skeletal size by stimulating GH secretion and acting directly through receptors on the bone. Long bones are the arm and leg bones, where there is typically a sexual dimorphism with males having longer arms and legs than females. Martin, et al. hypothesized that homosexual men with reduced androgen exposure would have shorter long bones than male heterosexuals and also that homosexual women with increased androgen exposure would have longer long bones than heterosexual women.

7. Skeletal Dimorphism * * * • Both males and females with a female partner preference had larger arm length:stature ratio • Females with a male partner preference had significantly shorter legs than homosexual females Martin, et al., 2004

8. Finger Digit Ratios • Another example of androgen exposure and bone growth • Heterosexual females have a higher 2D:4D ratio, that is, the index and ring fingers are closer to the same length • Heterosexual males usually have a index finger that is shorter than the ring finger • Homosexual women have a pattern not different to that of males Greene, 2002

9. Androgen and Cognition • Homosexual women performed better on 3 types of spatial ability tests than heterosexual women • Men also outperform women on these tests (not shown on graph) Van Anders, et all, 2005 • On a verbal fluency test, homosexual males performed between heterosexual females and heterosexual males • Homosexual males had a cognitive pattern similar to heterosexual females Greene, 2002

10. Otoacoustic emissions • Otoacoustic emissions are weak sounds produced by the cochlea in the inner ear which are produced spontaneously and in response to a weak click. • Females emissions are more spontaneous and stronger in response to a click • In opposite sex twin pairs, the females have a male-like pattern due to the androgen exposure of the male twin during development • Female homosexuals respond at levels between a heterosexual male and heterosexual female Greene, 2002

11. Zebra Finches • Injection on ED 5 with fadrazole, an aromatase inhibitor. • Overall behavior did not differ between control females and fadrazole females. • Males spent less time with treated females and more time with control females. • Beak color of treated females was more masculine-like.

12. Zebra Finches • In treated females: • 75% had 1 testis and 1 ovotestis • 25% had testicular but not ovarian tissue • Females treated with fadrazole shifted toward masculinized partner preference. Adkins-Regan, et al.,2001

13. Homosexual Rams Roselli et al. found that male oriented rams receive lower than normal androgen stimulation of the brain mRNA levels for aromatase in the oSDN were higher in males than females, and were higher in female-oriented males than male-oriented rams

14. Rams, LH, and ERs • Rams were classified as heterosexual (mounting females) or homosexual (mounting other males) • LH levels of both groups of male rams were lower than female sheep • However, ERs in the amygdala were much higher for heterosexual rams than either the homosexual rams or females • ERs in the hypothalamus, anterior pituitary, and POA were no different among the three groups Perkins, et al., 1995

15. Androgen implanted goldfish • Female goldfish were implanted with androgen or blank implants • Androgen implanted females spent significantly more time in proximity to stimulus females than stimulus males Thompson et al., 2004

16. Role of PGE2 • Female rats that received PGE2 neonatally were capable of expressing all of the male sexual behavior except ejaculation • A COX inhibitor was used because estradiol upregulates COX-2 in the developing POA • Male rats treated with indomethacin, a COX inhibitor, had decreased male sexual behavior Amateau & McCarthy, 2004

17. Congenital Adrenal Hyperplasia Females • An autosomal recessive disease • Over-exposure to androgens during fetal development which can cause genital ambiguity or masculinization in genetic females • Control females and CAH females report no difference in the amount of homosexual experiences. • However, CAH females report higher rates of bisexual fantasy, fewer heterosexual experiences, and lower rates of overall sexual experience Zucker, et al., 1996

18. Aromatase Deficiency • A heterosexual man in Italy presented with a mutation of the aromatase gene and hypogonadism • Only after a combined treatment of testosterone and estradiol did full sexual behavior return • Phases of treatment: • Phase 1 – testosterone alone • Phase 2 – washout from testosterone • Phase 3 – estradiol • Phase 4 – testosterone plus estradiol Carani, et al, 2005

19. Trp2 -/- • When mice have a non-functional Trp2 gene, they have vigorous and frequent mounting of both male and female mice • The frequency of male mounts is for the Trp2-/- is triple the frequency, with no change in the amount of female mounts • Therefore this is not a “confused” mouse who does not know the difference between males and females • Mechanism is not yet known McCarthy & Auger, 2002

20. A “Gay Gene”? • Hamer, et al., found a link between a marker on the X chromosome, Xq28, and homosexual men. • Rice, et al., studied the same marker in Canadian gay male sibling pairs and found no differences from the heterosexual population. • Aromatase cytochrome P450 also studied as a candidate gene in homosexual brothers, but no variations were revealed. • This debate will most likely continue…

21. Brain Differences in the Rat • SDN in the rat • Males are 5-7 times larger than females • Males deprived of androgen early have a small SDN • Females exposed to excess androgen during perinatal period will have a larger than normal SDN Gorski et al., 1982

22. Brain Differences in the Human • Hypothalamus • SCN • Population of AVP-expressing neurons in the SCN are 1.7 times greater and has 2.1 times as many cells in homosexual vs. heterosexual males. • Interstitial nucleus of the anterior hypothalamus (INAH – 3) is 2.8 times larger in the male • The weight of the INAH – 3 is reduced in homosexual males, although the number of neurons within the nucleus was only related to sex, and not related to sexual orientation Byne et al., 2001 • Anterior commissure • Larger in homosexual than heterosexual men Allan & Gorski, 1992

23. Fraternal Birth Order Correlation between birth order and homosexuality Also a correlation between birth order and birth weight Feminine boys with 2 or more older brothers weighed 385 g less than control boys May be due to an immune response by the mother with an anti-male antibody Blanchard, et al., 2002

24. Nicotine Effects • Prenatal nicotine exposure has masculinizing/defeminizing effects on female offspring and increases the probability of female homosexuality.

25. Maternal Stress • Maternal stress can lead to increased homosexuality • Most relevant during the first or second trimester for males • No specific time frame is known for females Swaab, 2004, Greene, 2003 • Stress in Guinea Pigs • Male guinea pigs whose mothers were stressed during pregnancy increased courtship behaviors in combination with play behaviors Kaiser et all., 2003

26. It’s simply not true! • There is a myth that social environment plays a large role in determining the sexual orientation of a person • Children raised by lesbian couples or transsexuals are not more likely to be homosexual themselves Swaab, 2004

27. More research, please! • Asexuals • A survey of 195 self reported asexuals found that: • More women than men self reported to be asexual • Asexual individuals are less educated than average • Asexual women had later onset of menarche • Asexual people were shorter and weighed less • Asexual people attended religious services more frequently than sexual population Bogaert, 2004 • Bisexuals

28. Why study this? • Vermont first state to allow civil unions • Massachusetts allows homosexual couples to marry • California grants registered domestic partners virtually every spousal right under state law except the ability to file joint income taxes • Connecticut second state to approve of same-sex civil unions • Laws take effect October 1, 2005 • Overall, the rest of the nation either has a ban on unions between homosexual couples or just does not legalize the union • No benefits (work, death, insurance) for partners

29. References • Adkins-Regan, E. & Wade, J. 2001. Masculinized Partner Preference in Female Zebra Finches with Sex-Reversed Gonads. Hormones & Behavior, 39: 22-28. • Allen LS, Gorski RA.1992 Sexual orientation and the size of the anterior commissure in the human brain. Proc Natl Acad Sci USA. 89:7199 –7202. • Amateau, S. & McCarthy, M. 2004. Induction of PGE2 by estradiol mediates developmental masculinization of sex behavior. Nature Neuroscience, 7(6); 643-650. • Blanchard, R., Zucker, K.J., Cavacas, A., Allin, S., Bradley, S.J., & Schacter, D.C. 2002. Fraternal Birth Order and Birth Weight in Probably Prehomosexual Feminine Boys. Hormones & Behavior, 41;321-327. • Bogaert, A.F. 2004. Asexuality: Prevalence and Associated Factors in a National Probability Sample. Journal of Sex Research, 41(3); 279-287. • Byne, W., Tobet, S., Mattiace, L.A., Lasco, M.S., Kemether, E., Edgar, M.A., Morgello, S., Buchsbaum, M.S., & Jones, L.B. 2001. The Interstitial Nuclei of the Human Anterior Hypothalamus: An Investigation of Variation with Sex, Sexual Orientation, and HIV Status. Hormones & Behavior,40; 86-92. • Gorski, R.A., Lippe, B.M., Green, R. 1982. Androgens and Sexual Behavior. Annals of Internal Medicine, 96(4); 488-501. • Greene, R. 2002. Sexual Identity and Sexual Orientation. Hormone, Brain, and Behavior, Volume 4. • Kaiser, S., Kruijver, F.P.M., Straub, R.H., Sachser, N., & Swaab, D.F. 2003. Early social stress in early male guinea pigs changes social behavior, autonomic and neuroendocrine function. Journal of Neuroendocrinology, 15; 761-769. • Martin, J.T., & Nguyen, D.H. 2004. Anthropometric analysis of homosexuals and heterosexuals: implications for early hormone exposure. Hormones & Behavior, 45; 31-39. • McCarthy, M.M. & Auger, A.P. 2002. He’s a lover, not a fighter – smell, sex, and civility. Trends in Endocrinology & Metabolism, 13(5);183-184. • Perkins, A., Fitzgerald, J.A., & Moss, G.E. 1995. A Comparison of LH Secretion and Brain Estradiol Receptors in Heterosexual and Homosexual Rams and Female Sheep. Hormones & Behavior, 29; 31-41. • Roselli, C.E, Stromshak, F., Stellflug, J.N., Resko, J.A. 2002. Relationship of seru testosterone concentrations to mate preferences in rams. Biol Repro, 67;263-268. • Swaab, D.F. 2004. Sexual differentiation of the human brain: relevance for gender identity, transsexualism, and sexual orientation. Gynecol Endocrinology, 19; 301-312. • Thompson, R.R., George, K., Dempsey, J., & Walton, J.C., 2004. Visual sex discrimination in goldfish: seasonal, sexual, and androgenic influences. Hormones & Behavior, 46; 646-654. • van Anders, S.M. & Hampson, E. 2005. Testing the prenatal androgen hypothesis: measuring digit ratios, sexual orientation, and spatial abilities in adults. Hormones & Behavior, 47; 92-98. • Zucker, K.J., Bradley, S.J., Oliver, G., Blake, J., Fleming, S., & Hood, J. 1996. Psychosexual Development of Women with Congenital Adrenal Hyperplasia. Hormones & Behavior, 30; 300-318.