Topics for this lecture: Sex determination Sexual differentiation Sex differences in behavior and...
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Transcript of Topics for this lecture: Sex determination Sexual differentiation Sex differences in behavior and...
Topics for this lecture:Sex determinationSexual differentiationSex differences in behavior and CNS development.
1) organizational effects ofgonadal steroids on CNSdevelopment2) 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)
• 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 testes-specific 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
FEMALEMALE
Female SDN-MPOA
Male SDN-MPOA
SNB
RDLN
DLN AMale
SNB
DLN
RDLN
BFemale
SNB Neurons
SNB Fragment
Non-SNB
Neurons
Figure 2
CentralCanalCentralCanal Blood Vessel
SNB Neurons
Figure 3
Glial Cells
Flutamide blocks androgen actionby 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.
Non-RDLN Neurons
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 determinationSexual differentiationSex differences in behavior and CNS development.
1) organizational effects ofgonadal steroids on CNSdevelopment2) our model system: SNB