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Hormones & Behavior, with some O.Chem 2550 > Chapter 3: Sex Determination and Differentiation
 > Flashcards

Chapter 3: Sex Determination and Differentiation
 Flashcards

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1
Q

3 Strategies used to understand human behavioral sex differences

A
  1. Animal models.
    Can experimentally control environmental conditions and manipulate hormonal conditions.
  2. People that have undergone anomalous sexual differentiation.
    “Experiments of nature”
  3. Different cultures to identify commonalities.
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2
Q

Causes of Sex Differences

The BIG QUESTIONS

A

Ultimate questions:
WHY do sexual dimorphisms arise?

Proximate questions:
HOW do sexual dimorphisms arise?

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3
Q

Why sex?

A

Asexual reproduction in insects and some vertebrates (i.e. fish and reptiles): parthenogenesis

There’s only one sex (female) in parthenogenic animals

All eggs genetically identical to mother

Pros & cons of asexual vs. sexual reproduction

Efficiency vs. evolutionary flexibility

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4
Q

Why sexual dimorphism?

A

Relationship between sexual dimorphism and mating system.

Sexual selection favors sexual dimorphisms.

Humans are mildly to moderately polygynous and display several sexual dimorphisms consistent with other polygynous species (Size, ornamentation)

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5
Q

Parthenogenesis

A

A type of asexual reproduction in which eggs can develop into offspring without fertilization.

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6
Q

polygynous

A

The condition or practice of having more than one wife at one time.
A mating pattern in which a male mates with more than one female in a single breeding season.

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7
Q

Sexual differentiation

A

the process of becoming a male or female

Although the two sexes are generally binary, genital development can fall anywhere along this continuum leading to ambiguous genitalia

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8
Q

Mammalian Sexual Differentiation

A

Begins at fertilization with chromosomal sex and depends on whether the sperm that fertilizes the egg carries an X or Y sex chromosome (Sex determination)

    - F: XX, homogametic
    - M: XY, heterogametic
  1. Chromosomal Sex (XX or XY)
  2. Development of the Gonads
  3. Development of the Accessory Sex Organs
  4. Development of the External Genitalia
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9
Q

Mammalian sexual differentiation: 


development of the gonads

A

Gonadal sex: internal organs

Early in ontogeny, XX and XY individuals have identical bipotential primordial gonads (germinal ridge)

SRY gene on Y chromosome –> testis-determining factor (TDF) –> medulla (middle) of germinal ridge becomes testes

No SRY –> no TDF –> cortex (outside) of germinal ridge becomes ovaries

Occurs approx. 6 weeks after conception

SRY can be express in one gonad and not the other

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10
Q

Mammalian sexual differentiation:

development of the accessory sex organs

A

Accessory sex organs connect gonads to outside environment

All individuals until the 3rd month have precursors to both male and female accessory sex organs

Wolffian system develops into seminal vesicles, vas deferens, epididymis

Müllerian sytem develops into fallopian tubes, uterus, cervix

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11
Q

Wolffian system

A

develops into seminal vesicles, vas deferens, epididymis

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12
Q

Müllerian system

A

develops into fallopian tubes, uterus, cervix

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13
Q

Male development requires 2 hormones from the testes

A

1) Testosterone:
Promotes development of Wolffian system.
Masculinizing effect.

2) Anti-Mullerian hormone:
Prevents Mullerian system from developing.
Defeminizing effect.

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14
Q

Female development does NOT require hormones

A

In the presence of ovaries or absence of gonads, Mullerian system develops and Wolffian system regresses

“DEFAULT” program
???

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15
Q

Masculinization

A

The induction of male traits.

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16
Q

Feminization

A

The induction of female traits.

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17
Q

Demasculinization

A

The removal of the potential for male traits.

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18
Q

Defeminization

A

The removal of the potential for female traits.

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19
Q

Mammalian sexual differentiation:

development of the external genitalia

A

**Males:
penis, scrotum.
Androgens are responsible for male external genitalia, particularly 5α-dihydrotestosterone, which is converted from testosterone by the enzyme 5α-reductase.

**Females:
labia, clitoris, and outer vagina.
No hormonal activity required for development of female genitalia

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20
Q

Female sex is ‘default’ ?

A

The idea that embryos develop as females unless they receive specific genetic instructions to become males may be over simplified

Female mice with mutation of Wnt-4 gene develop male sex organs

Wnt-4 normally acts to suppress the male sex system by preventing the production of testosterone and inhibiting the development of the Wolffian duct

Deleted Wnt-4 –> activation of the male pathway in female mice

Over-expressed Wnt-4 –> male feminization, indicating that it is able to block male development even in the presence of SRY.

Argues against the assumption that female development results from a lack of active signalling.

Male-typical gene expression is likely ACTIVELY REPRESSED by epigenetic mechanisms (biochemical gene silencing).

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21
Q

Chromosomes may also directly influence sex differences in brain and behavior

A

SRY mRNA has been detected in mouse brain (not just testes) during development.
May have other roles.

A number of genes are differentially expressed between male and female brains prior to gonadal formation

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22
Q

X chromosome inactivation

A

One X-chromosome randomly inactivated in each cell of females

Gene dosage equivalence with males

Females are a mosaic

Is inactivation random?
Is it complete?

23
Q

X chromosome escapees

A

Not all genes on x-chromosome are inactivated, so females sometimes get ‘double the dose’ of certain genes

That means, for these genes, females have 2x the gene, 2x the protein as males.

X- Escapees even differ between tissues!

24
Q

Disorders of Sex Development (DSD)

A

Anomalies in the process of sexual differentiation

Result of chromosomal or hormonal abnormalities

“Experiments of nature”

25
Q

There’s been NO record of viable organism that has a single Y chromosome

A
26
Q

Turner Syndrome (XO):

A

Female typical external appearance and genitalia

Ovarian underdevelopment

Require hormone treatment at puberty

Other hormonal abnormalities that slow growth as well as hearing loss, intellectual disability, kidney dysfunction

Severity depends on which parent they get their X from, it’s better if they get it from mom.

27
Q

Klinefelter syndrome (XXY):

A

Appear male but genitalia are underdeveloped

Usually sterile because of reduced sperm production

Gynecomastia, disproportionally long limbs

Severe learning disabilities

28
Q

XYY:

A

Male appearance but usually sterile

Above average height

Below average intelligence

Increased Aggression?

29
Q

Congential Adrenal Hyperplasia (CAH)

A

XY males are unaffected

Problem with synthesis of hormones in adrenal gland (which makes stress hormones).
ANDROGENS

Genetic (XX) females have masculinized genitalia with an ‘intersex’ appearance

Behavioral masculinization too…

Congenital adrenal hyperplasia (CAH) =
A genetic deficiency that results in the overproduction of androgens by the adrenal glands. This syndrome has no reported ill effects in males, but causes various degrees of masculinization of the external genitalia in females, which may lead to erroneous assignment of sex at birth.

30
Q

5α-reductase deficiency

A

XY males that lack the 5-alpha-reductase enzyme which converts Testosterone to 5-alpha-dihydrotestosterone (the androgen responsible for masculinization of the external genitalia).

Normal brain male development.

Have ambiguous external genitalia but development of testes and accessory sex organs not affected (because testosterone and anti-mullerian hormone function normally)

Raised as girls but at puberty, testosterone causes development of secondary sex characteristics and masculinization of external genitalia

Typically have male gender identity from childhood

Prenatal testosterone

Guevadoces of the Dominican Republic

Steroid 5alpha-reductase deficiency in man:
an inherited form of male pseudohermaphroditism

31
Q

Androgen Insensitivity Syndrome (AIS),

a.k.a., testicular feminization mutation (TFM) in rodents

A

XY genotype

Gonads develop as testes which release T and AMH

Genetic mutation prevents the formation of androgen receptors which disrupts normal development of the Wolffian system and external genitalia

Anti-Mullerian hormone still has a defeminizing effect

Normal-appearing female external gentalia, female appearance and female gender identity

Usually not discovered until puberty

UNAMBIGUOUS Female gender identity (no androgens acting on brain development)

Tons of hormone, bad receptors
Almost always retain identity as a woman, are usually very feminine.

32
Q

Hermaphrodites

A

Individuals who have both ovaries and testes

Extremely rare

33
Q

Organizational/Activational Hypothesis

A

Behavioral sex differences result from:

  1. differential exposure to hormones that act early in development to organize NEURAL circuitry underlying sexually dimorphic behaviors. SOFTWARE
  2. differential exposure to sex steroid hormones later in life that activate the neural circuitry previously organized. HARDWARE

William C. Young (1899-1965)

34
Q

Young’s classic experiment

A

William C. Young (1899-1965)

**Mating behavior in rodents is sexually dimorphic:
Females: lordosis
Males: mounting

  • *Rodent mating behavior under control of gonadal steroids:
    • Castration of adult males stops mounting behavior and T restores it.
    • However, adult females given T do not display increased mounting behavior (demasculinized)
    • Removing ovaries from adult females stops lordosis which is reinstated with ovarian steroids.
    • However, treating castrated males with ovarian hormones does not lead to lordosis (defeminized).
35
Q

Young’s classic experiment..

continued

A

Hypothesis: hormonal events early in development are important for adult reproductive behavior

Experiment:
T given to pregnant guinea pigs
As adults, female offspring were ovariectomized and given:
1) Estrogens & Progestins to stimulate female sexual behavior
2) given T to stimulate male sexual behavior

Results:
Female guinea pigs exposed to androgens prenatally display reduced lordosis and increased mounting.
No effect of early androgen exposure on male sexual behavior.

Conclusion: the potential for masculine or feminine behavior is organized by early exposure to hormones

**Guinea pigs are more like humans than rats and mice in their prenatal development.
This is why they are often used in studies of this type.

36
Q

Sensitive or Critical Period

A

A period of time when an animal is maximally sensitive to organizing effects of hormones to permanently change morphology and/or behavior

**Usually within the prenatal and/or perinatal period, depending on species
Rats: first 10 days after birth
Guinea pigs: halfway though their 69 day gestation period
Humans: end of first trimester and first few weeks of second trimester

Once the critical period has ended, no amount of hormones can have an organizational effect

We now think that adolescence may be an additional mini-critical period for sex specific brain development.
Especially for feminization

Sensitive period: not just when hormones usually act, but when hormones can even have any type of permanent effect.

37
Q

Activational Effects

A

Adulthood

No sensitive or critical period

Transitory

38
Q

Organizational Effects

A

Occurs before the brain matures

Critical period

Relatively permanent

39
Q

Organizational and Activational Effects of Hormones

A

Many adult behavioral sex differences in rats are organized and activated by hormones:
aggression, parental behavior, and emotional behavior

Organizational (

40
Q

For Females:

A

Organizational: nothing

Activational: Estrogens & Progestins

41
Q

Organizational and Activational Effects of Hormones

A

Exposure to androgens in early life permanently organizes the brain to permit the later expression of masculine behavior in response to activational effects of hormones.

In the absence of androgens, the brain & behavior develop in a female-typical fashion.

42
Q

Mechanism by which androgens masculinize the brain

A

Androgens play a direct role in the masculinization of the human brain.

But, in many animals, aromatization of testosterone into estradiol masculinizes the brain

Depending on the species (basically all non-primate species do something different), females are protected from estradiol by:
Alpha fetoprotein (mostly)
The placenta (a little)

But not the spotted hyena!

Hyenas don’t have alpha fetoprotein, so females in this species are pretty masculine-like.

43
Q

Masculinization and defeminization of brain and behavior are 2 different processes:

A

Both processes (in rats) depend on estradiol

Estradiol induces masculinization of the preoptic area via a downstream mediator (prostaglandin E2).

Treating baby female rats with the prostaglandin masculinizes copulatory behavior (masculinization), but leaves maternal behavior (feminization) intact.

Masculinized but not De-Feminized because need activtional hormones are still needed.

Treating baby males with inhibitor of prostaglandin synthesis leaves them de-masculinized but not feminized

CONCLUDE: 2 processes occurring side by side

44
Q

In rodents, estrogens derived from androgens are masculinizing to BRAIN.
In humans, just androgens!!

A

!!!!

45
Q

Two stage model for organizational effects 
on behavior

A

Perinatal

Adolescent

46
Q

Environmental Influences on Mammalian Sexual Differentiation

A

Intrauterine environment

Maternal stress

Differences in maternal care

Exposure to environmental chemicals

47
Q

Effects of the intra-uterine environment

A

Female rat pups’ position in the uterine horn can impact her physiology and behavior as an adult

Fetal girls pups situated between two fetal males are affected by the males’ hormones

2-M females are more aggressive (some masculination), less attractive to males (different behavior? different pheromones?) and have longer ovarian cycles (their brains are a bit different)

48
Q

Effects of maternal stress

A

Male offspring of mothers stressed during pregnancy:

  • -Produce less androgen
  • –Have impaired mating behavior
  • –Have certain parts of the nervous system that are more female typical
  • -Show more parental behavior
  • -Are less aggressive
  • -Exhibit demasculinized rough and tumble play

Mom is more stressed… Fetal boys are less masculine and less de-feminized.
Mom’s stress hormones, glucocorticoids may interfere with fetal boy androgens

49
Q

Effects of Maternal care

A

Mother rats spend more time licking male pups than female pups because they prefer the chemosensory cues associated with male pups urine

Mother rats who are rendered unable to smell their pups do not lick their male pups more and these males show altered patterns of male sexual behavior as adults suggesting that males require maternal licking to develop normal adult sexual behavior

Females who are licked more as pups are more attentive mothers

Male pups are more demanding of and more receptive to mom’s care

50
Q

Endocrine disrupting chemicals (EDC) mimic the effects of estrogen, androgen or thyroidple: DDT

A

mimic the effects of estrogen, androgen or thyroid hormones

example: DDT

DDT:
Flame-Retardent.
Stays around in the environment.
Can act on hormone receptors.

51
Q

Atrazine

A

Endocrine disrupting chemical

Commonly used herbicide

Does not affect adult frogs but modest levels affect sexual development in frogs producing testicular abnormalities

Amphibians in particular are very sensitive to hormone disruptions relative to other animals, likely because their metamorphosis process is driven by hormones

Potent organizational effects

52
Q

Bisphenol A

A

Excreted estrogens derived from birth control pills

Effects of EDC in humans include:
Males: Double the rate of cryptorchidism (no testes) and hypospadias (urethra opens on underside of penis) in boys, triple the rate of testicular cancer, reduced sperm counts

Females: MUCH earlier onset of puberty

Body fat is one of the triggers for puberty, so larger girls tend to start puberty earlier.
But the obesity issue is not enough to explain these huge effects across the board.
Greasy birth control hormones urinated into the water supply

53
Q

Environmental sex determination

A

NO sex chromosomes in some species of reptiles

Temperature involved in sex determination

Effects of temperature can be overriden by steroids

If eggs are incubated at male-producing temperatures but given estrogen, then females develop.

If eggs are incubated at female producing temps but are given androgen, males develop.

54
Q

Sequential hermaprodites

A

animals that begin life as one sex then change to the other sex as adults

Seen in many species of fish in response to their social environment

Example: clownfish (Nemo lol)

“If Mom dies, Dad becomes a female!”

Hormones & Behavior, with some O.Chem 2550 (6 decks)

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