Transcript SNB_Lect1R

Topics for this lecture:
Sex determination
Sexual differentiation
Sex differences in behavior
and CNS development.
1) organizational effects of
gonadal steroids on CNS
development
2) our model system: SNB
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Sexual Determination
(mammalian)
• SRY (Sry) gene (Sex-determining Region of the
Ychromosome)
• Pepetide is AKA Testis Determining Factor-Probably a transcription factor--binds DNA
• Found in XY and XX men. Absent in XX
females and some XY females--frameshift/point
mutation in some XY females
Sexual Determination
(mammalian)
• Sry expressed in indifferent gonad just prior to and
during differentiation--if expressed becomes testis, if not
becomes ovary.
• SOX9--probably also a transcription factor (HMG box
present)
• SOX9--expressed in male but not female genital ridge
just after Sry
• Absence of SOX9 in XY individuals usually results in
female development--also other problems-die at birth
Sexual Determination
(mammalian)
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SF1--Steroidogenesis Factor 1
Might be activated by SRY
Might be a cofactor of SRY
activates genes for enzymes in steroid synthesis
absence results in complete failure of adrenal
development and part of the hypothalamus
Remember: SRY is the genetic
“switch” in sex determination
Presence of SRY is a necessary but not
sufficient condition for male sex
determination
Ovarian Development
• DAX1--gene on X chromosome--double dose
disrupts testicular development
• Wnt4a--expressed in genital ridge--shuts off in
XY individuals but stays on in XX--deletion
results in poorly formed ovary with some testesspecific markers (AMH and testosterone
synthesizing enzymes)
After genetic sexual determination,
sexual differentiation is largely driven
by gonadal steroids.
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What are Steroid Hormones?
• Hydrophobic
• Derived from Cholesterol
• Molecules generated by Endocrine System
which sends signals to various parts of body
– e.g., Aldosterone, Cortisol, Sex Hormones
– Synthesized by gonads, adrenal, and most likely
brain
Androgens
• Testosterone (potent)
• Androstenedione (can be converted from and to
testosterone and not very potent)
• Dihydrotestosterone (is synthesized from
testosterone in a one-way reaction--also potent)
Estrogens
• Estrone (E1--relatively weak)
• Estradiol (E2--relatively potent--can be sythesized
from testosterone in a one-way reaction)
• Estriol (E3--relatively weak)
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What about sex differences in
behavior?
• Are there sex differences in behavior?
• What is/are the explanation(s) for these
differences?
• Could these sex differences in behavior be due to
culture in humans?
• Could these sex differences in behavior be due to
biology, possibly organizational and activational
effects of steroid hormones?
Organizational Sexual Differentiation
Driven Largely
by Gonadal Steroids
• androgens--periphery and spinal cord
• estrogens--brain
What about CNS anatomy?
“…a more subtle change reflected in
function rather than in visible structure
would be presumed.”
-Phoenix, Goy, Gerall, & Young, 1959
MALE
FEMALE
Female SDN-MPOA
Male SDN-MPOA
RDLN
SNB
Male
DLN
A
RDLN
SNB
Female
DLN
B
Figure 2
NonSNB
Neurons
SNB Fragment
SNB Neurons
Central
Central
Canal
Canal
Blood Vessel
Glial Cells
SNB Neurons
Figure 3
Flutamide blocks androgen action
by binding to androgen receptors,
preventing androgens from binding
the receptors. Flutamide seems to
act as a “pure” anti-androgen-doesn’t have any androgenic
properties.
RDLN Neurons
Non-RDLN Neurons
Figure 4
Summary:
1) We are studying the organizational effects of hormones
--relatively permanent actions of hormones on the nervous system
in early development, during a critical/sensitive period.
2) Specifically, we are studying the organization impact of androgens
during development.
3) We will examine the SNB neurons, a set of neurons known to
be sexually dimorphic and that innervate a sexually dimorphic
target (BC/LA) muscle.
4) We will also examine the RDLN neurons that don’t innervate a target
that has dramatic sex differences (flexor digitorum brevis).
Topics for this lecture:
Sex determination
Sexual differentiation
Sex differences in behavior
and CNS development.
1) organizational effects of
gonadal steroids on CNS
development
2) our model system: SNB