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SNB
Gonadectomy and treatment with Testosterone (T) of adults do not alter the
dimorphism in male and female
SNB
The dimorphism do not
depend by estrogens
(TFM male rats have high
levels of cerebral
estrogens and estrogen
receptors)
The dimorphism do not
depend by genome, but
by absence of interaction
of androgens with their
receptors
Breedlove and Arnold, Brain Res, 1981
RESULTS
The sexual dimorphism of SNB do not depend by
hormonal status of the adult and genome, but probably it
is an organizational effect due to the interaction
androgens-receptors during the critical period of the
development.
DLN MODEL OF RAT
EXPERIMENTAL DESIGN
Single subcutaneous injection with Testosterone
propionate (TP 1mg) at P2
RAT
Perinatal TP injection
*
masculinizes DLN of
females
The cell number
increases to intermediate
levels between control
females and males
Androgens are involved
in the sexually dimorphic
development of DLN
Jordan et al, Brain Res, 1982
SNB AND DEVELOPMENT
*
Single subcutaneous injection with TP (1mg) at P2 and sacrifice at 2 months
Perinatal T induces masculinization (increase in number of neurons) of SNB in female rats
Breedlove et al, Brain Res, 1982
Androgens are necessary for the sexually dimorphic
development also of the SNB
Mechanism(s) of Testosterone action ??
T ==== aromatization ==> E2
T ==== reduction
==> DHT
SNB AND DEVELOPMENT
NUMBER OF NEURONS
Neonatal EB injection in
females do not change the
number of the neurons
Aromatization of T is not
sufficient to induce the
dimorphic development of
the SNB
Single subcutaneously injection with estradiol benzoate (EB, 100g) at P2
Breedlove et al, Brain Res, 1982
• Probably androgens masculinize SNB of females directly acting on
the neurons
• Nevertheless, the target muscles contain DHT-R and ER and
respond with an increase of glucose-6P-dehydrogenase to E2 and
T, but not to DHT
• It is known that E2 affects the copulatory behavior in adult.
The dissociation between copulatory behavior and cell number in
SNB is partially due to the fact that SNB controls the sexual function
of the penis, but not the posture muscles (the copulatory behavior is
a complex function)
SNB AND DEVELOPMENT
male
female
antiandrogen+cx male
T female
There are different critical periods for
the differentiation of SNB? …………..
SNB AND DEVELOPMENT
MASCULINIZING EFFECT OF T
ON FEMALE RAT
Arnold, TINS, 1984
(16-22 days)
(1-5 days after birth)
(7-11 days after birth)
T prevents the death of motoneurons in the week before birth
SNB AND DEVELOPMENT
MASCULINIZING EFFECT OF DHT
ON FEMALE RAT
DHT rearranges
the neurons, but it
does not regulate
their number.
DHT address
neurons to the
appropriate target
(penis muscles)
Arnold, TINS, 1984
(16-22 days)
(1-5 days after birth)
(7-11 days after birth)
SNB AND DEVELOPMENT
MALE RAT
Arnold, TINS, 1984
Flut: flutamide (antiandrogen)
Androgens do not stimulate neurogenesis because this process
ends between prenatal-day 12 and 14
1 - Androgens prevent cell death in the week preceding birth. In
this period there is a peak of cell death and a peak of androgens
2 - Androgens are involved in specification and rearrangement of
neurons, not in the increase of their number. Androgens adress
motoneurons to innervate penis muscles