The long term objective of this research is to elucidate the control mechanisms which govern the maturation of a single follicle during the follicular phase of the menstrual cycle. Our previous work has demonstrated that the maturing follicle, via its secretion of estradiol, inhibits the growth of other follicles by suppressing gonadotropin secretion.
The specific aims of the current proposal are directed towards understanding why the growing follicle continues to mature in the presence of gonadotropin levels which are insufficient to maintain the growth of other less mature follicles. One specific hypothesis that we will test is that the maturing follicle exhibits a differential requirement for gonadotropins when compared with other less mature follicles. This could be accomplished by either escaping a dependence for follicle stimulating hormone or by acquiring the capacity to respond to both follicle stimulating hormone and luteinizing hormone. To test this hypothesis we will administer purified follicle stimulating hormone and luteinizing hormone to cynomolgus monkeys to initiate follicle maturation and thereafter reduce or eliminate the infusion of follicle stimulating hormone to determine if luteinizing hormone, alone or in combination with small amounts of follicle stimulating hormone, can continue to support the maturation of the preovulatory follicle. In addition, we will examine gonadotropin receptor levels and gonadotropin sensitivity in individual follicles during the course of follicle maturation in order to provide an explanation, at the cellular level, which may account for altered gonadotropin sensitivity. We will also investigate whether the growing follicle produces substances which stimulate neovascularization such that, by the acquisition of a rich microvascular network, the growing follicle may selectively receive gonadotropic hormones. In addition to providing basic information regarding the control of ovarian function, these studies are likely to provide new insights with respect to the hormonal requirements for follicular maturation and as such may have direct application in the treatment of some forms of infertility in humans.
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