The overall goal of this research is to elcuidate the phyisological mechanisms which govern the maturation of a single preovulatory follicle during the primate menstrual cycle. Our work to date has documented that the feedback relationship between ovarian steriods and gonadotropin secretion is the essential component of the hypothalamic-pituitary-ovarian axis by which the presence of a maturing follicle arrests the development of less mature follicles. Further, we have shown that the maturing follicle continues its growth in the presence of gondatropin concentrations which are unable to initiate the maturation of less mature follicles which explains how the maturing follicle is protected from its own inhibitory influences. During the proposed funding interval we will continue our use of the gonadotropin-pulsed macaque model to investigate the nature of the ovarian responses to gondatrophic hormones. Specifically, we will determine whether follicular growth in response to FSH is a threshold dependent phenomenon. In addition, we will investigate the ovarian mechanisms by which the maturing follicle acquires greater sensitivity to FSH, and whether the pathophysiological connection associated with polycystic ovarian disease is a direct consequence of an altered FSH:LH ratio. Lastly, we will utilize magnetic resonance imaging to measure growth rates of individual follicles as a function of gondatropin concentration as well as to study the ovarian microcirulation during follicle growth and atresia. In addition to providing basic information as follicular growth during the primate menstural cycle, it is expected that results from the proposed study will be of use to endocrinologists in the control of certain forms of infertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD012014-10
Application #
3311752
Study Section
Reproductive Biology Study Section (REB)
Project Start
1981-09-01
Project End
1992-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
10
Fiscal Year
1988
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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