neural organization under hormonal versus direct-genetic effects cynthia j. gill, ph.d. asst....
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
Neural organization under hormonal versus direct-genetic effects
Cynthia J. Gill, Ph.D.Asst. Professor of Physiology
Hampshire CollegeSchool of Natural Sciences
• essential brain area controlling female-typical sexual behavior
• sexually dimorphic in adult male and female whiptails
• site of estrogen sensitivity
Ventral medial hypothalamus
(VMH)
PC
V M H
DH
LTP
VE
TECT
Receptor mRNA expression in the adult VMH
0
5
10
15
20
25
30
35
40M
ean
in s
itu g
rain
s/ce
ll (+
SEM
)PR FemalesPR MalesER FemalesER Males
Progesterone Receptor Estrogen Receptor
Modified from Godwin and Crews, 1995
**
/ +E / +E / +E / +E
Injection blank(/) or estrogen (+E)
QuestionQuestion
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?
testosteronetestosterone estrogenestrogen
malesmales
femalesfemales
6 week exposure 1 week recovery
injection
Experimental procedure:
measure ER & PR mRNA expression in VMH by in situhybridization
PC
VMH
DH
LTP
VE
TECT
Gdx
SSV
SSV + estrodiol benzoate
SSV + estrodiol benzoate (high magnification)
FemalesMales
b
a' a'
b
a
c
0
15
5
10
25
20
30M
ean
in s
itu g
rain
s/cl
uste
r (+S
EM)
Progesterone receptor mRNA expression in the adult VMH
T/- T/E -/E T/- -/E -/- 6 week exposure/injection
Modified from Wennstrom, Gill and Crews, 1998
a a
b
a
b
c
FemalesMales
0
15
5
10
25
20
30M
ean
in s
itu g
rain
s/cl
uste
r (+S
EM)
Estrogen receptor mRNA expression in the adult VMH
T/- T/E -/E T/- -/E -/-
6 week exposure/injection
a
b
b
Gill, Crews & Wennstrom, 2004
• 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
ConclusionsConclusions
….like behavioral sensitivity.
.…like brain morphology.
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
E PR
-
POA VMH
Male +T
Male, no T
FemaleE PR
cell death
Model: Variation in cell survival early and cell connectivity later
QuestionQuestion
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
C. inornatus
C. inornatus
C. costatusor C. burti
C. uniparens
F1 parthenoform
X
X
C. uniparens - created by blocking estrogen production in the embryo
C. inornatus
Sexual &
Parthenogen &(‘male’ is genetically female,hormonally male)
Progesterone receptor mRNA expression in the VMH
0
5
10
15
20
25
30M
ean
grai
ns/c
lust
er (+
SEM
)SSVEB
One day old Thirty days old
female male female "male"__________________ sexual
__________________ sexualfemale male female "male"
__________________ parthenogen
__________________ parthenogen
Estrogen receptor mRNA expression in the VMH
0
2
4
6
8
10
12M
ean
grai
ns/c
lust
er (+
SEM
)SSVEB
One day old Thirty days old
female male female "male"__________________ sexual
__________________ sexualfemale male female "male"
__________________ parthenogen
__________________ parthenogen
**
*
*
• 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.
Conclusions IIConclusions II
.…like brain morphology.
….like behavior.
Undergraduate research assistants: Michelle Embleton
Molly Fant Jen Lui Kavita Juneja Laura Young
Drs. David Crews and Kira Wennstrom
AcknowledgementsAcknowledgements
BEHAVIOR
OVARY
OVIDUCT
HORMONES
Female-like Male-like Female-like Male-like
Ovulation Ovulation
Estradiol
Progesterone
BRAIN mRNA
POA
VMH
PR
ER
Sexually dimorphic Fos responses to mating stimuli
Female response to chemosensory cues and mating
Male response to chemosensory cues and mating
0
5
10
15
20
25
30 JGDataFemalesJGDataMales
Mea
n in
situ
gra
ins/
clus
ter (
+SEM
)Progesterone receptor mRNA expression in the adult VMH
T/- T/E -/E -/- -/E T/- -/E -/- T/- T/E
a
aa
b
b
c
0
5
10
15
20
25
30 JGdataFemalesJGdataMales
Mea
n in
situ
gra
ins/
clus
ter (
+SEM
)Estrogen receptor mRNA expression in the adult VMH
T/- T/E -/E -/- -/E T/- -/E -/- T/- T/E
b
a
b