SNB

Gonadectomy and treatment with Testosterone (T) of Gonadectomy and treatment with Testosterone (T) of adults do not alter the dimorphism in male and femaleadults do not alter the dimorphism in male and female

Breedlove and Arnold, Brain Res, 1981

SNB

The dimorphism do The dimorphism do not depend by not depend by genome, but by genome, but by absence of absence of interaction of interaction of androgens with androgens with their receptorstheir receptors

The dimorphism do The dimorphism do not depend by not depend by estrogens (TFM male estrogens (TFM male rats have high rats have high levels of cerebral levels of cerebral estrogens and estrogens and estrogen receptors)estrogen receptors)

RESULTSRESULTS

The sexual dimorphism of SNB do not depend The sexual dimorphism of SNB do not depend

by hormonal status of the adult and genome, by hormonal status of the adult and genome,

but probably it is an organizational effect but probably it is an organizational effect

due to the interaction androgens-receptors due to the interaction androgens-receptors

during the critical period of the during the critical period of the

development. development.

DLN MODEL OF RATDLN MODEL OF RAT

EXPERIMENTAL DESIGNEXPERIMENTAL DESIGN

Single subcutaneous injection with Single subcutaneous injection with Testosterone propionate (TP 1mg) at P2Testosterone propionate (TP 1mg) at P2

Jordan et al, Brain Res, 1982

Androgens are Androgens are

involved in the involved in the

sexually dimorphic sexually dimorphic

development of DLNdevelopment of DLN

RAT

Perinatal TP Perinatal TP

injection injection

masculinizes DLN of masculinizes DLN of

femalesfemales

The cell number The cell number

increases to increases to

intermediate levels intermediate levels

between control between control

females and malesfemales and males

**

Breedlove et al, Brain Res, 1982

Single subcutaneous injection with TP (1mg) at P2 and sacrifice at 2 monthsSingle subcutaneous injection with TP (1mg) at P2 and sacrifice at 2 months

SNB AND DEVELOPMENT

Perinatal T induces masculinization (increase in number of neurons) of SNB in female rats

**

Androgens are necessary for the sexually Androgens are necessary for the sexually

dimorphic development also of the SNBdimorphic development also of the SNB

Mechanism(s) of Testosterone action ??Mechanism(s) of Testosterone action ??

T ==== aromatization ==> E2T ==== aromatization ==> E2

T ==== reduction ==> DHTT ==== reduction ==> DHT

Breedlove et al, Brain Res, 1982

Single subcutaneously injection with estradiol Single subcutaneously injection with estradiol benzoate (EB, 100benzoate (EB, 100g) at P2g) at P2

SNB AND DEVELOPMENT

Aromatization of T Aromatization of T is not sufficient is not sufficient to induce the to induce the dimorphic dimorphic development of the development of the SNBSNB

Neonatal EB Neonatal EB injection in injection in females do not females do not change the number change the number of the neuronsof the neurons

NUMBER OF NEURONSNUMBER OF NEURONS

• Probably androgens masculinize SNB of females Probably androgens masculinize SNB of females

directly acting on the neuronsdirectly acting on the neurons

• Nevertheless, the target muscles contain DHT-R Nevertheless, the target muscles contain DHT-R

and ER and respond with an increase of glucose-and ER and respond with an increase of glucose-

6P-dehydrogenase to E2 and T, but not to DHT6P-dehydrogenase to E2 and T, but not to DHT

• It is known that E2 affects the copulatory It is known that E2 affects the copulatory

behavior in adult.behavior in adult.

The dissociation between copulatory behavior and The dissociation between copulatory behavior and

cell number in SNB is partially due to the fact cell number in SNB is partially due to the fact

that SNB controls the sexual function of the that SNB controls the sexual function of the

penis, but not the posture muscles (the penis, but not the posture muscles (the

copulatory behavior is a complex function)copulatory behavior is a complex function)

male female

antiandrogen+cx male T female

SNB AND DEVELOPMENT

There are different critical periods for the differentiation

of SNB? …………..

Arnold, TINS, 1984

MASCULINIZING EFFECT OF TON FEMALE RAT

(16-22 days)

SNB AND DEVELOPMENT

(1-5 days after birth)(7-11 days after birth)

T prevents the death of motoneurons in the week before birth

Arnold, TINS, 1984 (16-22 days)

SNB AND DEVELOPMENT

(1-5 days after birth)(7-11 days after birth)

DHT rearranges the neurons, but it does not regulate their number.

DHT address neurons to the appropriate target (penis muscles)

MASCULINIZING EFFECT OF DHTON FEMALE RAT

Arnold, TINS, 1984 Flut: flutamide (antiandrogen)

MALE RAT

SNB AND DEVELOPMENT

Androgens do not stimulate neurogenesis because Androgens do not stimulate neurogenesis because

this process ends between prenatal-day 12 and this process ends between prenatal-day 12 and

14 14

1 - Androgens prevent cell death in the week 1 - Androgens prevent cell death in the week

preceding birth. In this period there is a peak preceding birth. In this period there is a peak

of cell death and a peak of androgensof cell death and a peak of androgens

2 - Androgens are involved in specification and 2 - Androgens are involved in specification and

rearrangement of neurons, not in the increase rearrangement of neurons, not in the increase

of their number. Androgens adress motoneurons of their number. Androgens adress motoneurons

to innervate penis musclesto innervate penis muscles