Tuesday Oct 19

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Tuesday Oct 19
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Developmental role of hormones Organizational
effects - permanent effects on tissue
differentiation of body and brain Activational
effects - effects that occur later in life
mostly beginning at puberty
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Reproductive systems are made up of 3 categories
of sex organs I. Gonads - testes or
ovaries II. Internal sex organs Female -
uterus, fallopian tubes, vagina Male -
epididymis, vas deferens, seminal vesicles,
prostate III. External sex organs Female
- labia, clitoris, outer vagina Male - penis,
scrotum
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• I. Development of Gonads
• A. Males and females have identical immature
  gonads during first month of gestation
• B. During 2nd month, differentiation of immature
  gonads is controlled by presence/absence of
  hormones.
• MALES
• a gene on the Y chromosome causes production of
  testis-determining factor (tdf or the SRY gene) -
  early 2nd month
• testis-determining factor tells the immature
  gonad to become testes (male)
• in absence of gene and tdf, immature gonads
  become ovaries
• in presence, gonads become testes

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II. Development of Internal Sex Organs A.
2nd month - embryo has bisexual internal organs
alongside either testes or ovaries (the
gonads) In same person (male or female), the
precursors for both male and female internal
organs are present. Tissues that can become
female internal organs - Mullerian system
Tissues that can become male internal organs -
Wolffian system B. Whether male or female
internal parts development depends on the
hormonal environment !
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C. 3rd month (fetal period) MALE - To develop
male internal organs, testes (male gonads) must
begin to produce 2 hormones and receptors must
respond! 1. Anti-mullerian hormone - tells the
Mullerian (potentially female) system not to
develop Mullerian tissues have receptors for
anti-Mullerian hormone - when bound, tissues do
not develop into female internal sex organs 2.
Androgens - tell the Wolffian system to
develop into internal male sex organs Wolffian
tissues have receptors for androgens when bound
by androgens, male internal organs develop
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C. 3rd month (fetal period) - continued FEMALE
To develop female internal organs, hormones must
be absent. In absence of hormones, Mullerian
system develops into female internal sex organs.
Wolffian tissues disappear. No hormonal
stimulation is required (default
setting). Mullerian system develops into
fallopian tubes, uterus, internal vagina
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• III. Development of External Sex Organs
• A. In first 8 weeks of gestation, males and
  females have the same external appearance.
• B. During the 3rd month, male or female
  external sex organs develop.
• 1. MALES
• testes (gonads) produce dihydrotestosterone
• this triggers development of external sex organs
  - the penis and scrotum

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• III. Development of External Sex Organs
• A. In first 8 weeks of gestation, males and
  females have the same external appearance.
• B. During the 3rd month, male or female
  external sex organs develop.
• 2. FEMALES
• in absence of hormones, female external parts
  develop - the labia, clitoris and outer vagina

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• Reproductive System Development The Brain
• (as understood from research in animal models)
• Perinatal Period
• perinatal - around the time of birth
• first few days postnatal in the rat occur
  prenatally and postnatally in human
• androgens organize the development of the
  hypothalamus along the male pattern (control of
  future steady hormone release)
• absence of androgens, hypothalamus develops for
  future control of cyclical pattern of hormone
  release

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• Organizing effect of androgens in rat brain
  occurs through conversion of testosterone to an
  estrogen (estradiol) in brain.
• In male rats, estradiol (from testosterone)
  causes hypothalamus to develop in male pattern of
  hormonal control
• But female rats are not masculinized by
  estrogens - estrogens cannot enter brain - get
  bound by alpha-fetoprotein
• (In Human female - estrogens from Mom do not
  cross the placenta)

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• Sexual dimorphism in human brain
• preoptic area of hypothalamus is larger in males
  than females
• --------------------------------------------------
  ---------
• connections between hemispheres are usually
  larger in females
• differences in cortical maturation rate - males
  slower to develop assymmetry
• subtle differences in hippocampus
• subtle differences in thalamus

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What if hormones are not allowed to act on
receptors and trigger development? Gonads? Inter
nal sex organs? External genitalia? Brain and
behavior?
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Abnormalities of Sexual Development 1. Genetic
abnormalities that interfere with receptor
development Androgenic Insensitivity
Syndrome Persistent Mullerian Duct Syndrome
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Abnormalities of Sexual Development 1. Genetic
abnormalities that interfere with receptor
development Androgenic Insensitivity
Syndrome Persistent Mullerian Duct Syndrome
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Androgen Insensitivity Syndrome Result Normal
testes develop and produce testosterone and
anti-mullerian hormone. No response no internal
male sex organs develop. But anti-Mullerian
hormone still prevents development of female
internal sex organs Later, external genitalia
develop as female due to absence of response to
male hormones At puberty, female body develops
due to small amounts of estrogen produced by
testes.
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Androgen Insensitivity Syndrome No active
androgens, develop as female. But anti-Mullerian
hormone prevents development of internal sex
organs only. Female in all respects - brain,
behavior, and outward appearance - but a
chromosomal male Case Study - Anne
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• Example 2 Persistent Mullerian Duct Syndrome
• XY males with no receptors for anti-Mullerian
  hormone
• normal response to testis-determining factor and
  androgens
• testes develop normally
• testes produce anti-Mullerian hormone (AMH) and
  androgens as they should
• What happens next?

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• Example 2 Persistent Mullerian Duct Syndrome
• testes produce anti-Mullerian hormone (AMH) and
  androgens as they should, but
• no receptors to allow suppression of female
  internal organs react normally to androgens
• Result male and female internal sex organs
  develop
• perinatally, androgens act to produce external
  male anatomy
• male function inhibited by presence of female
  sex organs

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Abnormalities of Sexual Development 1. Genetic
abnormalities that interfere with receptor
development Androgenic Insensitivity
Syndrome Persistent Mullerian Duct Syndrome 2.
Abnormalities in sex chromosomes Turners
Syndrome (XO)
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Turners Syndrome - XO - missing a sex
chromosome (usually from Dad) - missing possible
contribution of X or Y How will the body
develop? Gonads? Internal organs? External
sex characteristics? Brain programming? Puberty?
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• Turners Syndrome - XO - female phenotype
• How will the body develop?
• have no Y, so cannot develop testes
• without 2nd X, small, non-functional ovaries
  develop
• Mullerian system develops in absence of hormones
  as it should female internal sex organs
  (uterus, etc)
• absence of hormones, normal female external
  genitalia develop normal brain programming
• at puberty, ovaries do not produce enough
  hormones for normal secondary sex characteristics
  to develop or normal menstruation/fertility

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• Other features -
• affects 1 in 3000 females of all ethnicities and
  races
• some missing only part of 2nd X chromosome
• generalized growth defect ( 4 ft 9 in as adults)
• ovarian failure and lack of secondary sex
  characteristics at puberty
• infertile, but high tech pregnancies are
  possible
• some cognitive effects
• now given hormonal supplements from birth (ideal)

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Abnormalities of Sexual Development 1. Genetic
abnormalities that interfere with receptor
development Androgenic Insensitivity
Syndrome Persistent Mullerian Duct Syndrome 2.
Abnormalities in sex chromosomes Turners
Syndrome (XO) 3. Hormonal abnormalities in other
glands Adrenogenital syndrome
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• Adrenogenital Syndrome
• congenital adrenal hyperplasia - increased size
  and number of cells in the adrenal glands
• excessive release of adrenal androgens beginning
  in perinatal period
• What happens during the perinatal period with
  regard to sexual development?
• for males, earlier onset of puberty
• for females, major effects on postnatal
  development

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• Adrenogenital Syndrome
• What happens during the perinatal period with
  regard to sexual development?
• Normally, presence of androgens causes external
  male anatomy to develop
• Males with Adrenogenital Syndrome
• perinatal development of male anatomy proceeds
  normally
• excess androgens cause earlier onset of puberty

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• Females with Adrenogenital Syndrome
• prior normal prenatal development as females
• perinatal effects of androgens masculinize
  external anatomy
• extent of effects varies with ratio of
  androgens/estrogens
• born with enlarged clitoris and fused labia -
  may look more malelike externally
• delayed onset of menstruation due to androgens
• behaviorally, tomboys but later most are
  heterosexual, some bisexual, no increase in
  exclusive homosexuality

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Females with Adrenogenital Syndrome
Treatment 1) drugs to suppress production of
androgens 2) surgical correction of external
appearance
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Abnormalities of Sexual Development 1. Genetic
abnormalities that interfere with receptor
development Androgenic Insensitivity
Syndrome Persistent Mullerian Duct Syndrome 2.
Abnormalities in sex chromosomes Turners
Syndrome (XO) 3. Hormonal abnormalities in other
glands Adrenogenital syndrome -------------------
---------------------------------------------- 1.
Normal development with abnormalities produced by
surgical error during circumcision