Lecture 12: Sex steroids and the nervous system

Question 1

What are sex chromosomes?

Answer 1

the location of genes responsible for sex determination i.e. gonad development

Question 2

What is the testis-determining factor and which gene does it come from?

Answer 2

a transcription factor the determines development of male gonadal tissues
the SRY gene

Question 3

Which sex hormones do the male and female gonads synthesise?

Answer 3

male: testosterone is produced by the testes
female: estrogens and progesterone is produced by the ovaries

Question 4

What do sex chromosomes determine?

Answer 4

the primary types of circulating sex hormones

Question 5

What is the common precursor of sex steroids?

Answer 5

cholesterol

Question 6

What is the solubility of steroid hormones?

Answer 6

lipid-soluble so pass through all membranes

Question 7

What is aromatase expression critical for?

Answer 7

determining whether androgen or estrogen is the primary active factor

Question 8

How are sex steroids synthesised?

Answer 8

cholesterol -> progesterone -> testosterone

testosterone is converted to 5ɑ-dihydrotestosterone by 5ɑ-reductase and it is converted to 17-β-estradiol by aromatase

Question 9

What causes masculinization of genitalia? How do levels of testosterone change in males during puberty?

Answer 9

early (pre-birth; second trimester) transient synthesis of testosterone
testosterone levels increase at puberty to (relatively) constant adult levels

Question 10

How do levels of estrogen and progesterone change in females throughout their life?

Answer 10

circulating estrogens and progesterone from ovaries are low until puberty
cyclical patterns of estrogen and progesterone synthesis during adulthood and decreased synthesis in menopause

Question 11

What is sex steroid synthesis regulated by?

Answer 11

pituitary hormones (FSH, LH) that are released into the bloodstream

Question 12

What are levels and patterns of FSH/LH secretion determined by?

Answer 12

the hypothalamus

Question 13

What is hypothalamus activity determined by?

Answer 13

circulating hormone levels (feedback circuits) and other brain inputs

Question 14

What are gynandromorphs?

Answer 14

comprise a mixture of genetically male and female tissues but both sides of the brain will be exposed to the same circulating hormones, so any differences between sides must be due to genes

Question 15

How many genes are expressed at different levels in male vs. female brains BEFORE gonad formation (in mammals)?

Answer 15

> 50 genes

Question 16

What is sexual dimorphism?

Answer 16

permanent anatomical, physiological and behavioral differences between sexes

Question 17

What are examples of behaviours that differ between male and female?

Answer 17

courtship and mating, parenting, aggressive/defensive behaviours, release of pheromones

Question 18

What are contributors to sexual dimorphic behaviours?

Answer 18

sex-specific neurons

sex-specific expression of hormone receptors in neurons common to both sexes

Question 19

What do anatomical and physiological differences define? What are permanent anatomical and physiological differences initiated by?

Answer 19

sexually dimorphic behaviours

initiated by exposure to (or deprivation of) steroids during developmental critical periods

Question 20

Where do steroid receptors have discrete patterns of localisation?

Answer 20

in the developing and adult nervous system, so only a minority of regions become sexually dimorphic

Question 21

What is the mechanism of steroid action?

Answer 21

steroid (androgen or estrogen) binds to its specific cytoplasmic receptor (AR or ER, respectively)
steroid-receptor complex translocates to nucleus to activate specific response elements -> specific RNA and protein

Question 22

What is the duration of steroid action?

Answer 22

slow onset and offset (hours-days)

Question 23

When is estrogen a critical masculinizing factor?

Answer 23

in neurons that express aromatase AND estrogen receptors

Question 24

What happens if a neuron expresses aromatase?

Answer 24

within the neuron testosterone is converted to estradiol: actions can occur via estrogen receptors or via androgen receptors or via both receptor types

Question 25

What happens in neurons that express aromatase (in males)?

Answer 25

the transient rise in circulating testosterone during development causes a transient, local, intracellular rise in estrogen in those neurons and since these neurons also express ERs, this intracellular increase in estrogen will have an influence on the properties of these neurons via ERs

Question 26

Do intracellular actions of aromatase influence circulating estrogen levels?

Answer 26

no, these effects are local

Question 27

Why don’t maternal estrogens affect sexual differentiation of the fetal nervous system?

Answer 27

the fetus expresses high levels of ɑ-fetoprotein, which binds circulating estrogens

Question 28

Why doesn’t ɑ-fetoprotein bind local intracellular estrogens generated from testosterone in cells expressing aromatase?

Answer 28

so they can continue to have effects within the cells they are generated

Question 29

What can androgens and estrogens have powerful effects on? What can these effects enhance?

Answer 29

neuronal structure and function
these effects can enhance the sexual dimorphism established during development or initiate completely new changes in structure/function

Question 30

What are many of the steroid receptor-dependent activational effects mediated by?

Answer 30

the classical genomic pathway

Question 31

What may steroid receptor activation be coupled to?

Answer 31

other rapid effects on expression that are not mediated by steroid response elements

Question 32

What are steroid-receptor independent options?

Answer 32

rapid, non-genomic, steroid receptor independent effects to directly modulate other signalling pathways, second messengers, ion channels
long-lasting effects by affecting gene expression of target cells

Question 33

What are common types of effects of steroids?

Answer 33

neuronal survival, neuronal volume, connectivity, excitability (ion channel expression) and communication (NT synthesis / expression of receptors for NTs and trophic factors)