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The role of thecal androgen production in the regulation of estradiol biosynthesis by dominant bovine follicles during the first follicular wave^1,2

K. E. Valdez^*, S. P. Cuneo, P. J. Gorden^¶ and A. M. Turzillo^*,,,3

^* Physiological Sciences, and and Departments of Veterinary Science and Microbiology, and Physiology, and and Animal Sciences, University of Arizona, Tucson 85724; and and ^¶ Dairy Veterinary Services, Chandler, AZ 85225

³ Correspondence: U.S. FDA, Center for Veterinary Medicine, 7500 Standish Place, Rockville, MD 20855 (phone: 301-251-3315; fax: 301-594-2298; e-mail: adele.turzillo{at}fda.hhs.gov).

The first wave of follicular development following ovulation in cattle is characterized by selection and growth of a large, estrogenic dominant follicle. After the follicle becomes morphologically dominant, concentrations of estradiol in its follicular fluid decrease abruptly. The purpose of this study was to determine whether this decrease in estrogen production is caused by an insufficient supply of androgen from theca interna or decreased aromatization of androgen precursor by granulosa cells. Dominant follicles were collected from Holstein heifers on d 4, 6, or 8 of the first follicular wave (n = 5/d). Amounts of 17-hydroxylase mRNA in theca interna were sevenfold higher (P < 0.01) on d 4 than on d 8. After 3 h in culture, secretion of androstenedione by theca interna collected on d 4 (236 ± 44 pg/µg of protein) tended to be lower (P = 0.055) compared with d 6 (517 ± 162 pg/µg protein) and was lower (P < 0.05) compared with d 8 (387 ± 51 pg/µg of protein). In granulosa cells, amounts of aromatase mRNA decreased (P < 0.05) on d 8 compared with d 6 but not d 4. In vitro secretion of estradiol was higher in granulosa cells collected on d 4 (3.5 ± 0.8 ng/[10⁵ cells x 3 h]) compared with d 6 (1.8 ± 0.6 ng/[10⁵ cells x 3 h]; P < 0.05) and tended to be higher on d 4 than on d 8 (2.2 ± 0.2 ng/[10⁵ cells x 3 h]; P = 0.058). We conclude that the decrease in estradiol production observed during atresia of the dominant follicle is not due to lack of androgen substrate for aromatization or downregulated expression of the aromatase gene, but may be the direct result of decreased activity of the aromatase enzyme within granulosa cells.

Key Words: Bovine • Granulosa Cells • Ovary • Steroidogenesis • Theca interna

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