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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD012014-07
Application #
3311751
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-09-01
Project End
1987-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
7
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Magee-Women's Hospital of Upmc
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zeleznik, Anthony J (2004) The physiology of follicle selection. Reprod Biol Endocrinol 2:31
Zeleznik, A J (2001) Follicle selection in primates: ""many are called but few are chosen"". Biol Reprod 65:655-9
Ravindranath, N; Little-Ihrig, L; Phillips, H S et al. (1992) Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary. Endocrinology 131:254-60
Ravindranath, N; Little-Ihrig, L L; Zeleznik, A J (1992) Characterization of the levels of messenger ribonucleic acid that encode for luteinizing hormone receptor during the luteal phase of the primate menstrual cycle. J Clin Endocrinol Metab 74:779-85
Schwall, R H; Mason, A J; Wilcox, J N et al. (1990) Localization of inhibin/activin subunit mRNAs within the primate ovary. Mol Endocrinol 4:75-9
Bassett, S G; Zeleznik, A J (1990) Acute suppression of FSH secretion by oestradiol in the ovariectomized rhesus monkey. J Reprod Fertil 88:441-6
Ryan, K D; Robinson, S L; Tritt, S H et al. (1988) Sexual maturation in the female ferret: circumventing the gonadostat. Endocrinology 122:1201-7
Dubey, A K; Zeleznik, A J; Plant, T M (1987) In the rhesus monkey (Macaca mulatta), the negative feedback regulation of follicle-stimulating hormone secretion by an action of testicular hormone directly at the level of the anterior pituitary gland cannot be accounted for by either testosterone or es Endocrinology 121:2229-37
Zeleznik, A J; Wolf, G L (1987) Preliminary studies on the use of magnetic resonance imaging with Gd-DTPA to monitor ovarian function in subhuman primates. Biol Reprod 36:971-4
Zeleznik, A J; Hutchinson, J S; Schuler, H M (1987) Passive immunization with anti-oestradiol antibodies during the luteal phase of the menstrual cycle potentiates the perimenstrual rise in serum gonadotrophin concentrations and stimulates follicular growth in the cynomolgus monkey (Macaca fascicularis). J Reprod Fertil 80:403-10

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