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