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Activities of Glucose Metabolic Enzymes in Human Preantral Follicles: In Vitro Modulation by Follicle-Stimulating Hormone, Luteinizing Hormone, Epidermal Growth Factor, Insulin-Like Growth Factor I, and Transforming Growth Factor ß1¹

^a Leland J. and Dorothy H. Olson Center for Women's Health, Department of OB/Gyn, and Department of Physiology and Biophysics, University of Nebraska Medical Center, 984515 Nebraska Medical Center, Omaha, Nebraska 68198-4515

Modulation of glucose metabolic capacity of human preantral follicles in vitro by gonadotropins and intraovarian growth factors was evaluated by monitoring the activities of phosphofructokinase (PFK) and pyruvate kinase (PK), two regulatory enzymes of the glycolytic pathway, and malate dehydrogenase (MDH), a key mitochondrial enzyme of the Krebs cycle. Preantral follicles in classes 1 and 2 from premenopausal women were cultured separately in vitro in the absence or presence of FSH, LH, epidermal growth factor (EGF), insulin-like growth factor (IGF-I), or transforming growth factor ß1 (TGFß1) for 24 h. Mitochondrial fraction was separated from the cytosolic fraction, and both fractions were used for enzyme assays. FSH and LH significantly stimulated PFK and PK activities in class 1 and 2 follicles; however, a 170-fold increase in MDH activity was noted for class 2 follicles that were exposed to FSH. Although both EGF and TGFß1 stimulated glycolytic and Krebs cycle enzymes for class 1 preantral follicles, TGFß1 consistently stimulated the activities of both glycolytic enzymes more than that of EGF. IGF-I induced PK and MDH activities in class 1 follicles but negatively influenced PFK activity for class 1 follicles. In general, only gonadotropins consistently stimulated both glycolytic and Krebs cycle enzyme activities several-fold in class 2 follicles. These results suggest that gonadotropins and ovarian growth factors differentially influence follicular energy-producing capacity from glucose. Moreover, gonadotropins may either directly influence glucose metabolism in class 2 preantral follicles or do so indirectly through factors other than the well-known intraovarian growth factors. Because growth factors modulate granulosa cell mitosis and functionality, their role on energy production may be related to specific cellular activities.

¹ This research was funded by grants HD 28165 from the National Institute of Child Health and Human Development, NIH, and Olson Foundation to S.K.R.

² Correspondence. FAX: 402 559 6164; skroy{at}mail.unmc.edu

³ Current address: Dalores M. Terada, Department of Pharmacy, Creighton University Medical Center, Omaha, NE 68178.

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