The dynamic interaction between steroids and gonadotropins in the mammalian ovulatory cycle

The interrelationship between steroid hormone secretion and gonadotropin secretion during the human menstrual cycle is a set of complex interactions. The temporal relationship between estradiol and progesterone secretion, the preovulatory surge of gonadotropins and the time of ovulation, has been studied extensively. The median time interval between the first rise of estradiol, progesterone, LH and FSH, and ovulation has been estimated to be 82.5 hr, 7.8 hr, 32 hr and 21.1 hr, respectively. The median time interval between peak blood concentrations of estradiol, LH and FSH, and the time of ovulation is estimated to be 24, 16.5 and 15.3 hr. There is considerable individual variation in the above mentioned estimates. The rising levels of blood estradiol that are secreted by the maturing ovarian follicles appear to be the primary trigger for the surge of gonadotropins leading to ovulation. In the experimental animal, the estrogen effect takes place at the level of the hypothalamus in the release of LHRH and at the level of the pituitary in increasing its sensitivity to LHRH. There appears to be a good correlation between the nuclear translocation of occupied estrogen receptors in the hypothalamus and the pituitary and the manifestation of estrogen effects. In the human, a rise in progesterone begins to take place after the first rise in LH has occurred. Progesterone appears to have both a stimulatory and inhibitory effect on gonadotropin secretion in the experimental animal and the human. Thus it exerts a fine-tune modulatory influence of estrogen effects which include enhancement of the estradiol induced gonadotropin surge, and perhaps the initiation of the midcycle FSH surge in the human. The abrupt termination of the preovulatory gonadotropin surge is difficult to explain because the pituitary gland is not depleted of its gonadotropin content or its capacity to secrete gonadotropins. Preliminary results suggests that progesterone by exerting its inhibitory influence may be responsible for the termination of the gonadotropin surge. This hypothesis, however, needs careful confirmation. The effects of progesterone may be manifested at higher brain centers, the hypothalamus and the pituitary, and may involve not only the release of LHRH but also an alteration of the pulsatile pattern of release of LHRH. The recognition of these components, along with the presence and control of LHRH degrading enzymes in the hypothalamus and the pituitary, emphasize the complexity of the system and the need for further work to gain a better understanding of the steroidal regulation of gonadotropin secretion.