Topics for this lecture: Sex determination Sexual differentiation Sex differences in behavior and CNS development. 1) organizational effects of
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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 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? Are there sex differences in the CNS?
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 testesspecific 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
12 Steroid Hormone Action
13 Nothing
14 Effects of Gonadal Steroids
15 DOGMA Sexual differentiation of the CNS is driven exclusively by gonadal steroids
16 XX XY XX XY
17 DOGMA Sexual differentiation of the CNS is driven exclusively by gonadal steroids
18 Perinatal hormones control a masculine trait in the brain XY XX XX + Testosterone or Estradiol
19
20 Organizational Sexual Differentiation Driven Largely by Gonadal Steroids androgens--periphery and spinal cord estrogens--brain
21 What about CNS anatomy? a more subtle change reflected in function rather than in visible structure would be presumed. -Phoenix, Goy, Gerall, & Young, 1959
22 RDLN Male SNB DLN A
23 RDLN Female SNB DLN B
24 Figure 2 Non- SNB Neurons SNB Neurons SNB Fragment
25 Central Canal Blood Vessel Glial Cells SNB Neurons Figure 3
26
27
28 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.
29 Figure 1 Male Female RDLN SNB DLN
30 RDLN Neurons Non-RDLN Neurons Figure 4
31 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.
32 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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