1. 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

2. Nothing

3. 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

4. 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

5. 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

6. Remember: SRY is the genetic “switch” in sex determination
Presence of SRY is a necessary but not
sufficient condition for male sex determination

7. 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)

8. After genetic sexual determination, sexual differentiation is largely driven by gonadal steroids.

9. Nothing

10. 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

11. 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)

12. Estrogens Estrone (E1--relatively weak)
Estradiol (E2--relatively potent--can be sythesized from testosterone in a one-way reaction)
Estriol (E3--relatively weak)

14. Nothing

17. 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?

22. Organizational Sexual Differentiation Driven Largely by Gonadal Steroids
androgens--periphery and spinal cord
estrogens--brain

23. -Phoenix, Goy, Gerall, & Young, 1959
What about CNS anatomy?
“…a more subtle change reflected in function rather than in visible structure would be presumed.”
-Phoenix, Goy, Gerall, & Young, 1959

24. MALE
FEMALE

25. Female SDN-MPOA

26. Male SDN-MPOA

27. Male

28. Female

29. Figure 2
Non-
SNB
Neurons
SNB Neurons
SNB Fragment

30. Figure 3 Central Central Canal Canal Blood Vessel Glial Cells
SNB Neurons
Figure 3

32. Slide from Arnold, A. P. ,. Bottjer, S. W. ,. Nordeen, E. J
Slide from Arnold, A. P., Bottjer, S. W., Nordeen, E. J., Nordeen, K. W., & Sengelaub, D. R. (1987) Hormones and critical periods in behavioral and neural development. In J. P. Rauschecker & P. Marler (Eds.) Imprinting and cortical plasticity. New York: Wiley and Sons.

35. 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.

38. RDLN Neurons
Non-RDLN Neurons
Figure 4

39. Summary: 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).

40. 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