Brain sexual differentiation and gonadotropins secretion in the rat.

1. The present work deals with sexual differences in gonadotropin regulation in the rat and the role of sexual organization of the hypothalamus in determining such differences. 2. Sex differences between male and 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 gonadal hormones. In the rat this period starts a few days before birth and ends approximately 10 days after birth. Female rats treated during this 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 affected by events during the neonatal period, recent data question the "critical" 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 behavioral 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 depends on active hormonal estrogenic induction during a sensitive period of development. 6. Besides, during differentiation of male sexual brain function estrogens may be supportive, rather than directive, to the primary action of androgens. 7. Serotonergic, noradrenergic, and opioid 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 pretreatment, and history of release from feedback inhibition. 9. The characteristic pattern of gonadotropin secretion in the female infantile rat, which is sexually differentiated, can be related to an increase in hypophyseal receptors coupled to an increase in the intracellular calcium response to GnRH. Such events depend on the sexual organization 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 messengers may modulate high sensitivity. Neonatal androgenization of the hypothalamus may decrease the hypophyseal response to GnRH by an alteration in receptor concentration and signal transduction during the infantile period. 10. Finally, serotonergic, dopaminergic, opioid, and noradrenergic regulation of GnRH varies with increasing age, and the sexual organization of the hypothalamus by testosterone or estrogens is a determinant in such regulation.