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Neural organization under hormonal versus direct-genetic effects Cynthia J. Gill, Ph.D. Asst. Professor of Physiology Hampshire College School of Natural Sciences. Ventral medial hypothalamus (VMH). TECT. P. C. LTP. D. VE. H. V M H.
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Neural organization under hormonal versus direct-genetic effects Cynthia J. Gill, Ph.D. Asst. Professor of Physiology Hampshire College School of Natural Sciences
Ventral medial hypothalamus (VMH) TECT P C LTP D VE H V M H • essential brain area controlling female-typical sexual behavior • sexually dimorphic in adult male and female whiptails • site of estrogen sensitivity
/ +E / +E / +E / +E Injection blank(/) or estrogen (+E)
Question Since adult males have higher testosterone levels than adult females... is chronic testosterone exposure responsible for the steroid receptor expression differences observed between adult males and females?
Experimental procedure: testosterone estrogen females males 1 week recovery injection Gdx 6 week exposure measureER & PR mRNA expression in VMH by in situ hybridization
SSV + estrodiol benzoate (high magnification) SSV SSV + estrodiol benzoate
Progesterone receptor mRNA expression in the adult VMH 30 a a 25 a 20 Mean in situ grains/cluster (+SEM) 15 b 10 b c 5 0 T/- T/E -/E T/- -/E -/- 6 week exposure/injection Modified from Wennstrom, Gill and Crews, 1998
Estrogen receptor mRNA expression in the adult VMH 30 a 25 20 b Mean in situ grains/cluster (+SEM) b 15 10 5 0 T/- T/E -/E T/- -/E -/- 6 week exposure/injection Gill, Crews & Wennstrom, 2004
Conclusions • Estrogen-induced progesterone receptor mRNA is fixed in an adult • female, but responsive to testosterone environment in an adult male • Estrogen-induced estrogen receptor mRNA is fixed in an adult male, • but responsive to testosterone environment in an adult female .…like brain morphology. ….like behavioral sensitivity.
Testosterone ... • directly regulates expression of some genes • can be converted to estrogen by aromatization to regulate other genes • affects synaptic connectivity • affects the size of cells • affects cell survival
Model: Variation in cell survival early and cell connectivity later POA VMH Male +T - Male, no T E PR Female cell death E PR
Question Since adult males and females differ in hormone receptor induction... is the sensitivity the result of hormonal or direct-genetic effects during development?
Sexual, parthenogenic and sex-reversed whiptails Sexual & X C. costatus C. inornatus C. inornatus or C. burti X F parthenoform C. inornatus 1 Parthenogen & (‘male’ is genetically female, hormonally male) C. uniparens C. uniparens - created by blocking estrogen production in the embryo
Conclusions II • Estrogen-induced progesterone receptor mRNA expression is not • sexually dimorphic at one and thirty days of age • Estrogen-induced estrogen receptor mRNA is sexually dimorphic • at one and thirty days of age • The sex dimorphism in estrogen receptor mRNA expression is • reversed in very young animals and it is hormone dependant. .…like brain morphology. ….like behavior.
Acknowledgements • Undergraduate research assistants: • Michelle Embleton • Molly Fant • Jen Lui • Kavita Juneja • Laura Young • Drs. David Crews and Kira Wennstrom
Female response to chemosensory cues and mating Male response to chemosensory cues and mating
Progesterone receptor mRNA expression in the adult VMH a a a Mean in situ grains/cluster (+SEM) b b c T/- T/E -/E -/- -/E T/- -/E -/- T/- T/E
Estrogen receptor mRNA expression in the adult VMH a b Mean in situ grains/cluster (+SEM) b T/- T/E -/E -/- -/E T/- -/E -/- T/- T/E