1. Sex Differentiation and Dimorphism

2. Sex Differentiation and Dimorphism occurs during……
In utero
Development
Adulthood
This differentiation and dimorphism arises from circulation of sex steroids
Testosterone, Estrogen, Progesterone, 5ɑDHT

3. The Sex Steroids

4. Sex Steroids Invade the Cell Nucleus

5. Sex Differentiation in utero
….Begins with the presence or absence of the testes-determining SRY gene
..Spontaneous deletion and insertion of SRY gene
in mice results in XX mice with testes and XY mice
with ovaries
These four-core-genotype mice are powerful tools for studying sex chromosomal vs. hormonal influences on brain development, sleep, and reward-seeking

6. Sex Differentiation in utero
Müllerian Ducts
Wolfian Ducts + Secretion of Müllerian Duct inhibiting hormone (MIH)

7. Sex Differentiation in utero in reptiles is dependent on temperature

8. What Happens If Sex Differentiation in utero is Disrupted?
Great article about these individuals and the science behind the controversy
over their biological sex makeup in The New Yorker (2009):

9. Gender Identity Disorders Arising From Improper Sex Differentiation
Androgen Insensitivity
5-alpha-reductase deficiency
Chromosomal XY XX
Main Disruption
Non-functional androgen receptors
Lack enzyme required for adrenal synthesis of cortisol
Gonads
Testes/normal
Genitalia
Female (birth); puberty (birth)
Female (birth); variable virilization
Internal Sex Organs
Wolfian
Psychosexual
Female **not absolute**
Female or Male

10. Sex Differentiation Across Development
can be altered during a “critical period” by hormonal injections, gonadectomy, and subsequent hormone replacement
Historical example: In the 1800s, Roman Catholic Church would castrate young boys to prevent their voice from breaking during puberty since women were no allowed to sing

11. Organizational vs. Activational Sex Differentiation
Permanence
Yes No
Chronology
Early-life and Pre-Puberty (critical period)
Puberty and Post-Puberty
Organizational: hormonal manipulation permanently alters neurochemistry and behavior that persist after puberty (activational period)
Activational: hormone manipulation alters neurochemistry and behavior for as long as hormone is present

12. Experimental Strategy for Delineating Sex Differences in a Neonate

13. Experimental Strategy for Delineating Sex Differences in an Adult

14. Sex Differences in Brain Morphology (in the absence of hormone manipulation)

15. Sex Differences in the Volume or Size of Hypothalamic Centers
Male
Female
Bed nucleus of the stria terminalis
Anteroventral periventicular nucleus
Medial preoptic nucleus**
Parastrial nucleus
Sexually dimorphic nucleus of the preoptic area
Supraoptic nucleus**
Ventromedial nucleus**
**differences in synaptic amounts too**

16. Sex Differences in Size and Presence of Perineal Muscle
**Androgen-dependent (organizational)**
Anogenital distance: longer in males vs. females

17. Brains of Gynadomorphs
Staining for mRNA encoding for W chromosome
This is Pat. His right-side is male (ZZ).
His left-side is female (ZW).
Agate et al. 2003; PNAS
Staining for mRNA encoding for Z chromosome

18. (Bird) Singing as an Example of Sexual Dimorphism
right
left
HVC: song control nuclei

19. Sex Differences in the Size of Brain Structures Induced by Hormones
Gorski (1975): MPOA of males is bigger
Castrated males have smaller MPOA
Females treated with estrogen have larger (male-size) MPOA
HOW?

21. Sex Differences in Neuronal Function Induced by Hormones

22. Sex-Specific Behaviors Induced by Hormones

23. Relationship Between Sexual Intercourse and Hormone Circulation
Most non-human females: sexual desire is tightly gated by highly circulating levels of estrogen (“in heat”)
Human females: sexual desire is less associated with circulating estrogen levels but is also influenced by circulating testosterone levels
Lordosis: sexually receptive behavior in mammals

24. Estrogen and Progesterone Activation of Lordosis
Treating female mouse with estrogen ONLY = minimal lordosis
Treating female mouse with progesterone ONLY= nothing
Treating female mouse with progesterone THEN estrogen= minimal lordosis
Treating female mouse with estrogen THEN progesterone= full lordosis
Estrogen “primes” (increases the number) of progesterone receptors

25. Neurobiological Basis for Homosexuality
Size differences in the interstitial nuclei and suprachiasmatic nuclei of anterior hypothalamus
LeVay et al. 1991
Swaab and Hofman, 1990

26. Differences in Neuronal Activity with Hormonal Priming