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Steroid Hormones and Brain Function


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What are 4 tests of the hypothesis that sexual differentiation of the human brain is hormone mediated?
1) Congential Adrenal Hyperplasia

2) Testicularly Feminized Females

3) Children of DES exposed mothers

4) 5-alpha Reductase deficient populations
What are two two characteristics of Congentital Adrenal Hyperplasia?
1) A 21-hyroxlase deficiency prevents the formation of adrenal cortical steroids, and increases the formation of adrenal androgens.

2) Females are androgenized
What causes Testicularly Feminized Females and what is the result?
1) A defect in the androgen receptor

2) XY are fully feminzed both anatomically (external) and behaviorally.
What is DES and what is the result to offspring is if the mother is exposed to it?
1) diethylstibestrol is a potent estrogen receptor agonist

2) Children of DEM moms have normal sexual differentiation leading to the conclusion that sexual differentiation of the human brain is androgen receptor dependent.
What are 4 characteristics of 5-alpha reductase deficient populations?
1) phenotypically female at birth or ambiuous

2) raised as a female

3) convert to male as hormones increase at puberty

4) evidence for nature, not nurture driving sexual differentiation of the brain.
What 5 skills for which males are better than females?
1) rotation tasks

2) sptial tasks

3) target directed tasks

4) diembedding tasks

5) mathmatical reasoning
What are 4 tasks where females are typically better than males?
1) Preceptual speed

2) Verbal fluency

3) Fine motor coordination

4) Mathmatical calculation
What typical kinds of subjects do boy and girls draw? What happens if a child has CAH or TFM? What do these results imply?
Boys - moving objects, e.g. cars
Girls - people

If girl has CAH => see boy drawings
If boy has TFM => see girl drawings

=> hormonal affect on what they draw
What are three examples which indicate that not all sexual differentiation is hormonally mediated?
1) Embryo development is greater in males even before differentiation of the gonad.

2) Kanagroo - swxually dimorphic structures appear before differentiation of gonad

3) Zebra finches - Sexually differentiated neural circuit for song.
What is the general effect of estrogen on the hippocampus of the female rat?
Estrogen increases the number of spines on pyramidal cells. The estrogen receptors for the female are contained within interneurons. Estrogen results in a decrease of inhibition by these neurons => increased excitation of pyramidal cells => increase in number of spines.
Where are androgen receptors located within the hippocampus, i.e. which cells? What is the result of the androgen?
In the pyramidal cells for a male.

Androgen => increase in number of spines.
What is the substance that converts testosterone to estrogen?
What cells control GnRH? Where are they located?
parvicellular neurosecretory cells in the hypothalamus

Anterior hypothalamic preoptic area
Medial basal area
What are the gwo male hormones made by the testes?
testosterone and inhibiton
What happens to the serum concentration of LH after castration?
It goes up because there is no testosterone for the negative FB loop.
What two hormones both use the same adrogen hormone?
testosterone and dihydrotestosterone
What enzyme converts testosterone to dihydrotestosterone?
Why do we believe there is gene memory involved in restoring lordosis to a female rat that has had its ovaries removed?
There need to be too estrogen treatments in order to restore lordosis. By the time of the 2nd, the estrogen from the first is out of the blood stream.
Does the brain begin as female or male?
What is meant by masculination? Give six examples.
Development of male behavioral characteristics. For male rats:

1) mounting vs. Lordosis

2) rough and tumble play vs. hang out

3) improved spatial ability

4) Activity (stays on side of open space and doesn't move much) vs. runs round in center

5) Aggressive behavior - newcomer

6) Urinary posture.
What is meant by defeminization? When does this typically occur?
Loss of female behavioral characteristics.

Around birth.
What would happen if a female guinea pig were treated with testosterone prior to birth?
1) Penis formed and vagina closed

2) More aggressive behavior

3) Non functional ovaries
What will be the Lordosis quotient and # mounting attempts for the following:

1) F+T at P21 (after birth)
2) F+T just after birth
3) M-gx just after birth
4) M-gx at P21
1) LQ normal. Mounting absent

2) LQ low. Mounting significant

3) LQ high. Mounting lower than normal

4) LQ low. Mounting normal for a while
What does adult male chicken look like if

1) chick castrated?

2) gonads from another chick to castrated chick?
1) capon and not a rooster

2) rooster
If a male dog is castrated prior to puberty, what stance will it take when peeing?
It will stand up and won't lift its leg.
What will happen to a male mouse regarding biting:

1) Castrated

2) Castrated then treated with T
Reduction in biting

Increase in biting
What chemical ties up estrogen in a female both before birth and for a while after birth?
What is a functional difference between sexes?
Positive fb of estrogen in female only
What are 3 morphological differences between males and feamles
SDN-POS: 5-6x bigger in male

AVPV: 5x bigger in the female after puberty.

Spinal Nucleus of the Bulocavernosus is bigger in male.
What is the definition of a stressor?

What are the four types of stressors?
A stimulus that disrupts homeostatsis

1) SYSTEMIC or Physical
2) PROCESSIVE or Physchological
What are the four acute effects of glucorticoids?
Inhibit protein synthesis and accelerate protein catabolism

Increase Hepatic glucose metalbolism (gluconeogenesis)

Increase lipolysis in adipose tissue = rlease of glycerol and free fatty acids

Increaded muscle catabolism and release of amino acids
What kinds of dysregulation of the HPA axis has been reported in affective disorders that are associated with chronic elevated glucocorticoids?
Elevated glucocorticoid levels

Impaired negative feedback regulation, e.g. inability to respond to dexamethasone following a CRH challenge

Increased nuymbers of CRH and vasopressin containing neurons in the hypothalamus
What two types of receptors are involved with the downstream action of ACTH?

Which has low affinity for cortisol and which has high?
Glucocorticoid receptors and Mineralocorticoid receptors.

GR has a high affinity for cortisol => largely unoccupied.

MR has a low affinity for cortisol => 80% occupied at basal levels of CORT

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