BRAIN SEXUAL-DIFFERENTIATION AND GONADOTROPINS SECRETION IN THE RAT

1. The present work deals with sexual differences in gonadotropin regu lation in the rat and the role of sexual organization of the hypothala mus in determining such differences. 2. Sex differences between male a nd female rats, with regard to their control of gonadotropin secretion , go beyond whether or not gonadotropins are released cyclically. Rats show additional sex differences (a) in the response of gonadotropins to removal and imposition of negative feedback signals and (b) in the ontogeny of gonadotropin regulation from birth to puberty. 3. There is a sensitive developmental period during which sexual differentiation of neural substrates proceeds irreversibly under the influence of gona dal hormones. In the rat this period starts a few days before birth an d ends approximately 10 days after birth. Female rats treated during t his sensitive period with androgens or estrogens will permanently lose the capacity to release GnRH in response to estrogenic stimulation. 4 . Nevertheless although sexual differentiation is dramatically affecte d by events during the neonatal period, recent data question the ''cri tical'' nature of this period, as it has been shown that testosterone can still act on neural substrates well beyond (15 to 30 days of age) the neonatal period to defeminize and masculinize endocrine and behavi oral functions. 5. Furthermore, the capacity for the normal display of female sexual behavior and for the cyclic release of gonadotropins is not, as has been assumed, inherent to central nervous tissue but depe nds on active hormonal estrogenic induction during a sensitive period of development. 6. Besides, during differentiation of male sexual brai n function estrogens may be supportive, rather than directive, to the primary action of androgens. 7. Serotonergic, noradrenergic, and opioi d systems participate in the sexual dimorphism in gonadotropin control in adult rats. 8. The sex difference in the postcastration LH rise is dependent on the early sexual organization of the hypothalamus, even though in adulthood it can also be influenced by a variety of factors such as the stage of the estrous cycle, age of the animal, estradiol p retreatment, and history of release from feedback inhibition. 9. The c haracteristic pattern of gonadotropin secretion in the female infantil e rat, which is sexually differentiatied, can be related to an increas e in hypophyseal receptors coupled to an increase in the intracellular calcium response to GnRH. Such events depend on the sexual organizati on of the hypothalamus. In males the greater sensitivity to GnRH at 30 days is reflected in an increase in pituitary GnRH receptors but not in an increase in the magnitude of Ca2+ mobilization induced by GnRH, therefore it is probable that in this situation alternative second mes sengers may modulate high sensitivity. Neonatal androgenization of the hypothalamus may decrease the hypophyseal response to GnRH by an alte ration in receptor concentration and signal transduction during the in fantile period. 10. Finally, serotonergic, dopaminergic, opioid, and n oradrenergic regulation of GnRH varies with increasing age, and the se xual organization of the hypothalamus by testosterone or estrogens is a determinant in such regulation.