The pre- and postnatal influence of hormones and neurotransmitters on sexual differentiation of the mammalian hypothalamus.

A number of brain structures and a great number of brain functions have been shown to be sexually dimorphic. It has also been shown that development and differentiation of these structures and functions proceeds during a critical pre- and postnatal period of increased susceptibility, and is controlled by gonadal steroids and neurotransmitter substances. The brain of male and female mammals seems to be still undifferentiated before the period of increased susceptibility to gonadal steroids and neurotransmitters starts. Feminization of brain structure and functions, e.g., establishment of the cyclic LH-surge mechanism and the expression of lordosis behavior, seems to depend on the moderate interaction of estrogens with the developing nervous system. Defeminization and masculinization of brain functions seem to be established during interaction of the developing nervous system with androgens, which have to be converted, at least in part, into estrogens. Structural differentiation of the male brain, e.g., the sexually dimorphic nucleus of the preoptic area (SDN-POA), seems to be exclusively estrogen-dependent, during differentiation of male brain functions, however, estrogens may be supportive, rather than directive, to the primary action of androgens. The molecular mechanisms of sexual differentiation of the brain are not yet fully understood. It seems, however, that the priming action of gonadal steroids during the period of increased susceptibility is either mediated by neurotransmitters, or neurotransmitters modulate the priming action of gonadal steroids. In particular, the adrenergic, the serotoninergic, the cholinergic, and possibly the dopaminergic system were shown to have strong influences on sexual differentiation of brain structure and functions. In contrast to the great number of available studies on the influence of gonadal steroids on sexual differentiation of the brain, there are rather few studies available concerning the influence of neurotransmitter systems. The available results are partly contradictory, so that an interpretation must be done with caution and will leave plenty of room for speculation. Postnatal application of compounds which stimulate or inhibit adrenergic activity mainly affected the neural control of gonadotropin secretion, and had only minor influences on differentiation of behavior patterns. It seems, however, that adrenergic participation in the differentiation of the center for cyclic gonadotropin release is very complex and stimulatory and inhibitory components may operate simultaneously. Activation or inhibition of beta-adrenergic receptors during postnatal development was shown to impair the responsiveness of the center for cyclic gonadotropin release to gonadal steroids, and impairs the expression of ejaculatory behavior in male rats.(ABSTRACT TRUNCATED AT 400 WORDS)