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) 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

-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

MALE FEMALE

Female SDN-MPOA

Male SDN-MPOA

Male

Female

Figure 2 Non- SNB Neurons SNB Neurons SNB Fragment

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

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.

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: 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