Transcript SNB
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, 100g) 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