The central nervous system and disorders of ovulation in women.

Abstract The folliculotropin-secreting ability of the anterior pituitary depends on chemical stimuli transmitted to it by the hypothalamus via the hypophyseal portal blood system. The exact site of origin of these stimuli within the hypothalamus, the details of their chemical structure, and the physiologic processes that cause them to be formed and secreted into the portal system are still largely unknown. The prolactin-secreting ability of the pituitary, on the other hand, resides within the pituitary itself, the hypothalamus acting to inhibit this secretory activity; transmission of this inhibitory influence, which is also apparently chemical in nature, is also via the hypophyseal portal blood system. In the most general terms, then, the regulation of secretion of gonadotropins involves processes which modify the stimulating influence over folliculotropin secretion and the inhibiting influence over prolactin secretion. These modifying influences may affect both rates of change in the rate of secretion of each of the gonadotropins as well as the general rate of their secretion. An attractive explanation for the general method of regulation is that a primary influence, stimulatory for folliculotropin secretion and inhibitory for prolactin secretion, operates at maximal capacity except when it is subjected to inhibitory influences arising in neurons other than those included within the system of primary influences. The stimulating or inhibiting activity of neurons of the primary systems is conceived of as an intrinsic property of these neurons, while the inhibitory activities of the neurons which affect them (the secondary systems) are conceived of as being dependent on changes, physiologic or pathologic, in the internal and external environment. Thus, all events occurring outside the primary systems eventually affect the degree of activity of the primary systems by activating inhibitory influences in other parts of the hypothalamus or CNS. The type of change in pituitary secretion would depend, then, on which primary system was affected, to what degree it was affected, and the rate of change effected in its activity. One must admit, however, that an alternative explanation, in which events within or outside the organism activate otherwise dormant neurons which then directly stimulate folliculotropin secretion, is possible. The maximal rate of release of LH that leads to ovulation, therefore, may be due either to the sudden removal of an inhibitory influence over a hypothalamic stimulating system of LH secretion or to the sudden activation of a stimulating influence. In either case, the change in activity seems quite clearly to be a combination of the effects of the steroid hormones (estrogens and progesterone) secreted by the growing follicles and of some environmental factor on the hypothalamus. In the general light of these concepts of hypothalamic function, three groups of anovulatory disorders in women were considered: those due to or associated with a continuous secretion of progesterone (e.g., pseudocyesis and the persistent corpus luteum syndrome); those due to a selective depression of folliculotropin secretion without (e.g., hypogonadotropic amenorrhea) or with a concomitant secretion of prolactin (e.g., Chiari-Frommel and related syndromes) and without the secretion of progesterone as a factor contributing to the anovulation; and those associated with a maintenance of estrogen secretion and various degrees of follicle growth (e.g., Stein-Leventhal and related syndromes). In the anovulations associated with a persistent corpus luteum, the major abnormality may be a maintenance of prolactin secretion in the absence of those conditions that normally are associated with its secretion (such as pregnancy or lactation) and in association with conditions which prevent the normal regression of the corpus luteum. The combination of psychic disturbances and the effects of progesterone itself may be such that the primary inhibiting influence over prolactin secretion is maintained in a depressed state for abnormally long periods of time. This condition is comparable to that of physiologic pseudopregnancy in mammals like the dog. In most cases of hypogonadotropic amenorrhea, the causes for the depression of folliculotropin secretion are not known. In one variant of this condition, commonly seen in young pretty women in association with sexual frigidity and anorexia (although not to the extent seen in anorexia nervosa), it is suggested that a secondary neural-inhibiting influence, arising from the individual's conflict over the expression of a strong drive toward both sex and food, depresses the primary stimulating influence over folliculotropin secretion. Although the neural connection between this conflict and the inhibition it gives rise to are not known, the suggestion includes the possibility that the individual's renunciation of both food and sex is specifically responsible for this inhibition. In the variants of hypogonadotropic amenorrhea associated with galactorrhea, the possibility of a pituitary tumor or of some other type of intracranial pathology must always be considered, but in most cases the cause for the association is unknown, although the change is similar to that induced by the suckling stimulus. In the “constant estrus” type of anovulation, the neurological defect primarily involves the hypothalamic influences which stimulate maximal-rate LH secretion, those stimulating tonic secretion being relatively unaffected. The defect may arise within the CNS itself and may be one of a much higher level of inhibition over maximalrate LH secretion than normally exists or a much higher threshold for activation of a stimulating influence causing maximal rate LH secretion. The defect may also arise within the overy itself and may lead to the secretion of abnormal combinations of steroid hormones which produce the same kind of effect on the hypothalamus. In either case, a vicious cycle results, since a tonic rate of folliculotropin secretion cannot stimulate normal follicle growth and hormone secretion, and the latter is necessary for the changes in hypothalamic activity which lead to maximal rate LH secretion; similarly, an abnormal combination of steroids secreted by the ovary maintains the hypothalamus-pituitary system in a state of tonic secretion of folliculotropins and does not permit LH secretion to rise to its potential maximum.