Sex Hormones,the brain

and behavior

M.Prasad NaiduMSc Medical Biochemistry,

Ph.D,.

Definitions of SexGeneticGonadalHormonalMorphological

Behavioral (gender role behavior)Identity

Effects of Sex HormonesOrganizational Effects

structural sensitive period irreversible masculinization/defeminization

Activational Effects act on existing structure no sensitive period reversible

testes differentiate ovaries differentiate

Sexual DimorphismsPhenotypic differencesbetween males and females

They can be:anatomicalphysiologicalbehavioralcognitive

They can be:qualitativequantitiave

Hypothalamus

Adenohypophysis

Testes or Ovaries

Target tissues

Control ofSex Hormones

IndirectLoop

ShortLoop

DirectLoop

GnRH

LH, FSH

Testosterone or Estrogen &Progesterone

neural inputs

Bipotential tissues: Undifferentiated tissuethat can differentiate into either a male orfemale form.

Sexual Dimophisms: Structures, functionsor behaviors that differ qualitatively or quantitatively between the sexes.

Castrate male hamster at birth

Prototypical Experiment(Males)

(before period of brain differentiation)

Test in adulthood

place with receptive female

inject with testosterone

male typical behavior low

mounting, intromission (ejaculation not possible)

female-typical behavior highdarting, ear-wiggling, lordosis

place with maleinject with estrogen and progesterone

Neuter female hamster at birth andinject with testosterone

Prototypical Experiment(Females)

(before period of brain differentiation)Test in adulthood

place with receptive femaleinject with testosterone

male typical behavior high (mounting)

female-typical behavior low (ear-wiggling, darting, lordosis)

place with maleinject with estrogen and progesterone

Differentiation of the Brain

MasculinizationInduction of male characteristics

DefeminizationSuppression of female characteristics

Two processesboth are dependent on fetal androgens

Why aren’t all femalesmasculinized?

α-fetoproteinbinds to estradiol extracellularyand prevents entry into cell

Kelley, D.B. (1988) Ann. Rev. Neurosci.,11, 225-251.

Ripple effects in brain sexual dimorphisms

♂

♀

Steroid Hormones

cholesterol

Hypothalamus

Adenohypophysis

Testes or Ovaries

Target tissues

Control ofSex Hormones

IndirectLoop

ShortLoop

DirectLoop

GnRH

LH, FSH

Testosterone or Estrogen &Progesterone

neural inputs

Hypothalamus

Adenohypophysis

Adrenal Cortex

Target tissues

Control ofStress Hormones

IndirectLoop

ShortLoop

DirectLoop

CRF(aka CRH)

Corticotrophin(aka ACTH)

Cortisol or Corticosterone

neural inputs(limbic system)

This is usually referred to as the “HPA axis,”but is now often called the “LHPA axis.”

estradiol

aromatase 5-alphareductase

cholesterol

DHT

Suppose there is a deficiency of either21-hydroxylase or 11-β hydroxylase.

cholesterol

estrodiol DHT

aromatase 5-alphareductase

cholesterol

Sex differences in cognition

Studies of mathematically gifted

Effects of brain damage

Anatomical studies of brain laterality

Functional (fMRI) studies of brain laterality

♂

♀

Brain Laterality

LeftPositive

RightPositive

Females Males

Totals

Totals

15/111(9%)

16/103(16%)

100/246(41%)

120/276(43%)

115/357(32%)

136/379(36%)

31/214 220/522(14%) (42%)

Geshwind’s Theory of

Cerebral Lateralization

Geschwind, N. & Galaburda, A.S. (1987) Cerebral lateralization. Cambridge, MA:MIT Press

McManus, I.C. & Bryden, M.P. (1991) Geschwind’s theory of cerebral lateralization:Developing a formal, causal model. Psych. Bull., 110, 237-253.

Hypothalamus

Adenohypophysis

Testes or Ovaries

Target tissues

Control ofSex Hormones

IndirectLoop

ShortLoop

DirectLoop

GnRH

LH, FSH

Testosterone or Estrogen &Progesterone

neural inputs

perform well on verbal and motor taskspoorly on spatial tasks

perform well on spatial tasks,poorly on motor and verbal tasks

Activational Effects of SexHormones on Cognition

Possible activational effectsof sex hormones on cognition

de Lacoste-Utamsing, C. & Holloway, R.L. (1982)Sexual dimorphism in the human corpus callosum.Science, 216, 1431-1432.

Splenium

Gladue, Green & Hellman (1983) Science, 225, 1496-1499.

Gladue, Green & Hellman (1983) Science, 225, 1496-1499.

LeVay, S. (1991) Science, 253, 1034-1037

Size related to sexual identitynot sexual orientation