Sex Differentiation and Dimorphism

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

The Sex Steroids

Sex Steroids Invade the Cell Nucleus

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

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

Sex Differentiation in utero in reptiles is dependent on temperature

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): http://www.newyorker.com/reporting/2009/11/30/091130fa_fact_levy

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

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

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

Experimental Strategy for Delineating Sex Differences in a Neonate

Experimental Strategy for Delineating Sex Differences in an Adult

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

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**

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

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

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

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?

Sex Differences in Neuronal Function Induced by Hormones

Sex-Specific Behaviors Induced by Hormones

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

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

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

Differences in Neuronal Activity with Hormonal Priming