Lecture 7: Sex-differences in Neural Circuit Development Flashcards
Signals that affect the developing brain (neurogenesis, proliferation,
differentiation, synaptogenesis) released by different developing organs:
- Cortisol and Corticotropin-releasing
hormone (CRH) - Adrenocorticotropic hormone (ACTH)
- Insulin-like factors (IGFs)
Testes-determining factor (SRY)
determines the development of male genotypic and phenotypic sex.
primary sexual characteristics
gonads and external genitalia
secondary sexual characteristics
includes differences in brain structure and behaviours
Cholesterol
precursor for testosterone (T) and estradiol
T causes masculinization of the
fetus at
7-20 weeks
some T is converted to…
estradiol in the brain → ALSO contributes to masculinization of the brain
feminization of the brain
Lack of hormones in fetal females
pathway of cholesterol
cholesterol
progesterone
testosterone -> aromatase -> estradiol
testosterone -> reductase -> dihydrotestosterone
α-fetoprotein (AFP)
- in fetal circulation
- Binds maternal E with
higher affinity than T
protects females against
potential masculinization
and de-feminization of the
brain by maternal E
Sexual Differentiation of the Brain
* In females
Pre- and post-natal: no H →
brain is feminized
- Puberty: P and E from
ovaries activate female‐specific behaviors
Sexual Differentiation of the Brain
*in males
Peri-natal (mice)/fetal
(human): T from testes
masculinize the brain
- Puberty: T activate
male‐typical behaviors
The organizational–activational hypothesis =
The production of sex hormones at puberty activates brain regions that were ‘organized’ during early development
Direct effects of gonadal
steroids on neurons
alter permeability and electrical
activity, NT availability
Indirect effects of gonadal
steroids on neurons
regulation of expression of genes that masculinize or feminize the brain (changes in cell # via regulation of proliferation and/or apoptosis, regulation of differentiation, signalling, connections, etc.)
- As TF
- via epigenetic regulation
Neural Circuit
Dimorphisms – Motor
Control Example
Rodents
Spinal nucleus of the bulbocavernosus
(SNB) in males innervates the
bulbocavernosus muscle of the penis
- absent in females
Neural Circuit
Dimorphisms – Motor
Control Example
humans
Onuf’s nucleus in both males and females
- Dimorphic ventrolateral group (VL)
- Bulbocavernosus muscle smaller in
females
Influence of sex hormones in neuron
numbers - The anteroventral paraventricular nucleus (AVPV)
a collection of DA neurons is larger in females than in males
Estradiol in developing brain
promotes apoptosis in males
Influence of sex hormones in neuron
numbers - sexually dimorphic nucleus of the preoptic area (SDN-POA)
is larger in males than in females
Estradiol in developing brain inhibits
apoptosis in males
