Sex steroids

Question 1

What is SRY and where is it found?

Answer 1

Controls directly transcription as a transcription factor that determines the development of the testes, found on the Y chromosome.

Question 2

Where are the sources of sex steroids

Answer 2

Primary gonads, minor adrenal cortex.

Question 3

Why is aromatase so critical?

Answer 3

It is so critical as it changes androgens into estrogens.

Question 4

Please outline the pathway resulting in the 5 alpha dihydrotestosterone (androgen) and 17 Beta Estradiol (estrongen)

Answer 4

Cholesterol—Progesterone—Testerone (5 alpha reductase)–5 alpha dihydrotesterone.

Cholesterol—Progesterone—Testerone (aromatase)— 17 beta estradiol.

Question 5

Explain the difference in temporal changes in steroid synthesis

Answer 5

Males- early transient (pre birth, second semester) of testerone causing masculinisation of genetalia.
Levels increase at puberty to relatively constant adult levels.

Females circulating estrogens and progesteone are low until puberty. We get cylical patterns during adulthood once puberty hits, decreased synthesis in menopause.

Question 6

Brain regulation of gonadal steroid synthesis

Answer 6

Driven by pitutary hormones. Hypothalamus (GnRH)- LH (testers for progesterone) and FSH (ovaries results in the production of progesterone and estrogen)

Question 7

What are Gyandromorphs

Answer 7

Comprise of a mixture of genetically male and female. tissues are both XX and XY. Both sides of the brain are exposed to same circulating hormones, so differences must be due to genes.

Question 8

What is the evidence for hormone independent genetic effects?

Answer 8

Zebra finch and in mammals- may not be as easily recognsied but greater than 50 genes are expressed at different levels before gonad formation.

Question 9

Organisational effects determine the way in which the mature NS will be constructed and then subsequently behaviour. Outline the reversible and irreversible effects of this process.

Answer 9

Exposure to steroids in the critical periods lead to permanent anatomical, physiological and behavioural differences— sexual dimorphism (Even upon removal of steroid you are stuck with these features.
Activational effects- describe the phenomenon whereby if steroid receptors continue to be expressed after birth, steroids can have further reversible effects.

Question 10

It is known that steroid receptors have a discrete pattern of localisation in the developing and adult NS, so only minority of regions are sexually dimorphic they are involved in?

Answer 10

Mating, parenting, aggressive/defensive behaviours, release of phermones.Steroid receptors make the hormones localised rather than ordinary diffuse nature

Question 11

Where are some of the denesities of the estrogen receptor

Answer 11

Septum, preoptic area, hypothalmus, pituary and midbrain.

Question 12

How many types of estrogen receptors are there?

Answer 12

2 types (Alpha and beta)- few areas have both.

Question 13

Outline the direct genomic mechanism for E2,

Answer 13

binds to Cytoplasmic receptor translocates to nucleus to activate specific response elements such as gene expression - slow onset and offset (hours-days) in contrast to NT

Question 14

Estrogen is a critical masculinising factor

Answer 14

In neurons expressing aromatase testosterone is converted to estradiol. T enters in presence of aromatase converted to estradiol or direct effects on androgen receptors. The transient rise in T during development causes a transient local, IC rise in e- initiating changes in neurons expressing ERs

Question 15

What about maternal estrogens?

Answer 15

Do not effect sexual differentiation in the fetal nervous system. Fetus binds high levels of alpha fetoprotein which binds circulating estrogens. Note that aromatase is located in specific populations of neurons and is IC therfore estrogens generated from testerosterone produced within these neurons are protected.

Question 16

Throughout adulthood androgens and estrogenes have powerfule effects on neuronal structure and function- these can enhance sexual dimorphism established during development but are often reversible- sustained though effects continue. What are examples of this context?

Answer 16

• Examples of context:
– Normal oestrus/menstrual cycles
– Hormonal treatments (e.g., anti-androgens for some types of cancer) –prostate cancer
– Reduced hormone levels with ageing or disease
– – [Puberty]

Question 17

Not all steroid receptors are activated by the classical genomic pathway (slow onset and slow offset) how can they be organised than?

Answer 17

Coupled to other more rapid events or effects on expression that are not mediated by steroid response elements, such as a membrane ER and get 2MS effecting processes.– Rapid, non-genomic, steroid receptor independent effects to directly modulate other signalling pathways, second messengers, ion channels
– Slow, long-lasting indirect effects by affecting gene expression of target cells ¬¬cascades in the NS.
– e.g., estrogen effects on neurotrophic factor expression
– affect neuron the initital or the organ.
– More than one mechanism may be activated in a neuron: can be difficult to define.

Question 18

An example of the effects of steroids is the neurogenesis in song birds what is this about?

Answer 18

– Males produce complex songs in the breeding season but females do not.
– • In some species, females can learn songs if exposed to androgens early enough.
– • Dimorphism in the end-organ (syrinx) and its nerve supply (number of neurons and their synapses).
– Neurogenesis- upon breeding season.- grow and divide- sing new songs- make new connections- controlling airflow allowing the bird to see.

Question 19

What some other effects of steroids?

Answer 19

– Neuronal survival –promote survival under stress
– Neuronal volume
– Connectivity:
o Dendritic length, branching, spines
o – Axon collaterals
– Excitability:
– - Expression or activity of ion channels
– Communication:
o – Neurotransmitter synthesis
o – Expression of receptors for transmitters and trophic factors

Changes depend on binding site- as well steroid expourse.

Question 20

Pain was an active area of research which of these were more prevalent.

Answer 20

Female- or male-specific (obvious because difference in organs.
–	Endometriosis 
–	Vulvodynia
–	Menstrual pain 
–	Prostatitis 
More prevalent in females 
–	Fibromyalgia 
–	Interstitial cystitis/bladder pain syndrome
–	Temperomandibular disorder 
–	Migraine 
More prevalent in males 
–	Cluster headaches 
–	Gout

Question 21

What aspects of pain were effected?

Answer 21

– prevalence of some types of pain
– – pain threshold, intensity and quality
– – efficacy of analgesics –
– pharmacokinetics of analgesics

Question 22

Pain and analgesia can be effected by

Answer 22

– Menstrual cycle, menopause 
–	 Endocrine disorders
–	  Exogenous estrogens 
–	Estrogen signalling blockers 
–	Aging

Question 23

What are some challegnes with the field in relation to pain.

Answer 23

– Steroid receptors expressed by subpopulations of neurons in many but not all parts of the pain-related neural circuitry: many potential sites of action
– – Numerous possible targets of steroid receptor independent actions Actions not described by the receptors.
– – Experimental designs to detect different types of steroid action in vivo
– – Controlling for stage of cycle can be challenging
– – Many publications do not provide sufficient information on sex and stage of cycle and/or are not controlled properly

Question 24

A specific example of unexpected sex differences are in spinal microglia signalling

Answer 24

Blocking microglia have been proposed because they have been linked to driving some pain states- almost all studies have been down in males. Recent studies showed that blocking microglia in females was actually ineffective.Mechanism in males involves T cells: different therapeutic approach.