Hormones and Behavior

February 25, 2021

Some anecdotes on sexual differentiation
• When TDF is present with the SF-1 (steroidogenic factor 1) protein, the
two form a transcription factor that regulates expression of another
member of the SOX family, SOX9, required for testicular development.

• more recent lines of evidence suggest that expression of a gene called

Wnt4 (wingless-related MMTV integration site 4) is required for normal
ovarian development.

• Four core genotype mice - remove SRY gene from the Y chromosome –
can also insert SRY as a transgene on another chromosome (allows
comparisons of males with ovaries, females with testes, etc)

• In females, there is a gene called Coup-tfII that is expressed to suppress

Wolffian development. If this gene is removed, female mice develop both
ducts. Unclear in males if Coup-tfII is suppressed by androgens in males.
Why Don’t Maternal Estrogens
Masculinize the Brains of Females?
Sex Determination in Birds
Sex Determination
- Phenotypic Male Morphs in Midshipmen Fish -

Type I and II Males

Type I reach sexual

maturation earlier and
are territorial and ‘sing’
to females.

Type II males have high

testosterone

11-ketotestosterone not
present in females or
Type II Males
Some turtles, lizards,
alligators and snakes can
alter sex of progeny by
altering the amount of time
that they spend on the nest
….i.e. how warm the eggs
get.
Sex Differences
in Brain
Why should we be interested in sex
differences, sex differentiation, etc?
 Interstitial Nuclei of the Anterior
Hypothalamus (INAH)
in Humans
INAH-1 larger in males than females (Swaab
& Fliers, 1985)

Wait! No sex difference in INAH-1, but males

have larger INAH-2 and 3 (Allen et al., 1989).

Simon LeVay (1991). INAH-3 larger in

heterosexual men than homosexual men and
women.
Sexual Dimorphisms in Brain – Relation
to Behavior?
Many sex differences identified
• Nucleus size
• Brain neurochemistry
• Neural Connectivity
• Enzyme activation
• Receptor Distribution
In mammals, no good link to function.
Many questions still unanswered
Is larger to promote sex-specific behavior or suppress opposite sex behavior
 5-α Reductase
Deficiency
Chrom: XY
Gonads: Testes (SRY)
Ducts: Wolffian (T)
Genitals Feminized (No DHT)
Brain: Exposed to T/E2

** Genitals form into a

penis around the
time of puberty **
CAH
CAH Females
• lack of 21-hydroxylase enzyme which converts
cholesterol to cortisol

Chrom: XX
Gonads: Ovaries (No SRY)
Ducts: Mullerian, maybe some Wolffian (some T)
Genitals Partially Feminized (varying degrees)
Brain: Exposed to androgens/estrogens
Digit Ratio

Thought that 2D:4D ratio reflects prenatal androgen

exposure.
2D:4D ratio ~1 in females; <1 in males
Gay men have finger ratio lower than straight men
!"#$%&'()*+,"-%.%/)$%0.+#1.2*0-"+3!456+0*+
).2*07".+%.#".#%$%8%$1+#1.2*0-"+39:56+
• XY individuals insensitive to androgens (dysfunctional
receptors)

• diagnosis often occurs at puberty when there is a failure

to menstruate

• treatment is usually to remove the testes and give

estrogens to induce secondary female sex
characteristics.
Chrom: XY
Gonads: Testes (SRY)
Ducts: None (MIH and not sens. to T)
Genitals Feminized (no androgen receptors)
Brain: Likely exposure to E2