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Sex, Sexuality, and the Brain: The Neurobiology
Alina Konnikova ‘11 and Daniel Sanchez ‘11 Biology Department, Lake Forest College, Illinois 60045 Introduction
Sexual Dimorphism in Animals
Sexual Development & Brain
Development Controlled by Pituitary Gland
Sexual Syndromes
Turner’s Syndrome
47-XYY Syndrome
• Hypothalamus
controls the pituitary
gland
• Pituitary gland is
also known as
“master gland”
Klinefelter’s syndrome
• Pituitary releases
gonadotropic
hormones
Physiological dimorphisms in hawk moth and songbirds
correlate with the dimorphisms in the brain
Homosexuality & the Brain
Gonad Development
Sexual Dimorphism and Human Brain
Animals
• Sex reversal on the
Y-chromosome
• SRY is a sole
determinant for male
genotypic and
phenotypic sex
MRI analysis suggests that males have bigger brain and
amygdala than females
Sexual Behavior and the Brain
Hormonal Involvement and the Brain
Cholesterol
Progesterone
Testosterone
Estrogen
Aromatase
• Male brain during second trimester is masculinized by estrogen
• Sexual dimorphism is also located in the hypothalamus
• SDN-POA lesions result in altered sexual behavior
• Male genatalia are masculinized by testosterone
Mutations of fruitless
lead to improper
courtship in
Drosophila males
Humans
fMRI shows different
areas of activation in
hypothalamus
between heterosexual
and homosexual
individuals
References
1. Purves, Dale, Augustine, George J., Fitzpatrick, David, Hall, William C., LaMantia,
Anthony-Samuel, McNamara, James O., and White, Leonard E. Neuroscience.
Massachusetts: Sinauer Associates, Inc., 2008
Acknowledgements
We thank Lake Forest College (Illinois) undergraduates of the BIO346 Molecular Neuroscience students Jaime Perez
‘10, Derek Atchely ‘10, Abegail Pipkorn ’10, Matthew Greenwood ‘10, Daryn Cass ‘10, Jon Flaskman ‘11, Liza
Pahmove, ‘11, Ashleigh Porter ‘11, and Keith Solvang ’11 for support and assistance. Special thanks to Dr. Shubhik
DebBurman for his never-ending guidance throughout this project.
Sex, Sexuality, and the Brain: Medical Mysteries
Alina Konnikova ‘11 and Daniel Sanchez ‘11 Biology Department, Lake Forest College, Illinois 60045 Sex Requires Kisses
Gap in Knowledge:
• Gonadotropin secretion results from GPR54
activation, what is the ligand for GPR54?
Too Aroused for Sex?
Gap in Knowledge:
•  Knowing that GA can activate other responses in
the brain, does it play a role in sexual behavior?
Anxiety/Stress?
Thirst
Hunger
Pain
Fear
Hypothesis:
• Kiss 1 is the ligand for GPR54
Hypothesis:
Major Findings:
• Generalized Arousal works to alter sexual
behavior and anxiety/stress
• Kiss -/- lack pubertal maturation (low levels of
testosterone and FSH), are sterile, and have
hypogonadotropic hypoganadism
d'Anglemont de Tassigny, X., Fagg, L. A., Dixon, J. P., Day, K., Leitch, H. G., Hendrick, A. G., et al. (2007). Hypogonadotropic hypogonadism in mice lacking a
functional Kiss1 gene. Proceedings of the National Academy of Sciences of the United States of America, 104(25), 10714-10719.
Sexual Orientation and the Brain
Major Findings:
• High generalized arousla is associated with high
sexual arousla
• Increased CNS arousal does increase anxiety/
stress like behaviors
Hypothesis:
Hypothesis:
• Sexual dimorphic features are located in the
amygdala.
-Males with deficient MIS are sexually males but
exhibit subtle feminization
Major Findings:
Major Findings:
• HoM & HeW connections in left amygdala,
contralateral amygdala, anterior cingulate
-Developing neurons have partial feminization of
their sexual dimorphism , even though they are
phenotypically and sexually males
- MIS is now being seen as a regulator for sexual
dimorphism
✓
Mullerian Inhibiting Substance
Testicular Hormone
Regression of Uterine
Precursor
Regression of Uterine
Precursor
?
Subtle Change
(Mullerian Ducts)
?
Sexual Reprogramming Error?
Gap in Knowledge:
• Many transcriptional regulators are shown to
prevent transdifferation of adult genital. What role
does FOXL2 play in sex reprogramming?
Hypothesis:
Hypothesis:
-Ablation of FOXL2 leads to sexual reprogramming
of the ovaries to testes
Major Findings:
Major Findings:
• Aromatase converts testerone to estrogen in
male brain
-Deletion of FOXL2 leads to immediate
upregulation of testes specific genes (SOX9)
-Ovarian phenotype is an active process
throughout life
Wu, M. V., Manoli, D. S., Fraser, E. J., Coats, J. K., Tollkuhn, J., Honda, S., et al. (2009). Estrogen masculinizes neural pathways and sex-specific
behaviors. Cell, 139(1), 61-72.
.
Mullerian Inhibiting Substance
Testicular Hormone
Gap in Knowledge:
• Male brain is masculinized during second
trimester of pregnancy, what is the role of
aromatase in the male brain masculinization?
• Aromatase is important in activation for malespecific aggressive and territorial behavior
Anxiety/Stress
Wang, P.Y., Protheroe, A., Clarkson, A.N., Imhoff, F., Koishi, K., and McLennan, I.S. (2009). Mullerian inhibiting substance contributes to sex-linked
biases in the brain and behavior. Proc. Natl. Acad. Sci. U. S. A. 106, 7203-7208.
Estrogen Masculinizes
• Estrogen masculines the aromatase-positive
neurons
✓
Recipe for Manliness
Gap in Knowledge:
• Sexual Dimorphism is known to be regulated by
many hormones, what role does MIS play?
Savic, I., & Lindstrom, P. (2008). PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and
heterosexual subjects. Proceedings of the National Academy of Sciences of the United States of America, 105(27), 9403-9408.
Sexual Behavior
Weil, Z.M., Zhang, Q., Hornung, A., Blizard, D., and Pfaff, D.W. (2010). Impact of Generalized Brain Arousal on Sexual Behavior. Proc. Natl. Acad. Sci. U.
S. A.
Gap in Knowledge:
• Are there sexual dimorphic features in the brain
of heterosexuals vs. homosexuals individuals?
• HoW & HeM connections in right amygdala,
caudate, putament, prefrotal cortex
Generalized Arousal Large Scale
Selective Breeding
SRY gene
SRY gene
+
-
+
Male
Female
-
Male
Female
Sox9
? ?
Foxl2, Dax1, Wnt4 Sox9
✓
Foxl2, Dax1, Wnt4
Uhlenhaut, N.H., Jakob, S., Anlag, K., Eisenberger, T., Sekido, R., Kress, J., Treier, A.C., Klugmann, C., Klasen, C., Holter, N.I., et al. (2009). Somatic
sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139, 1130-1142.