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Mineralocorticoid Synthesis During the Periovulatory Interval in Macaques¹

Department of Physiology,³ Medical College of Georgia, Augusta, Georgia 30912 California National Primate Research Center (CNPRC),⁴ Davis, California 95616 Department of Obstetrics, Gynecology, and Reproductive Sciences,⁵ University of Maryland School of Medicine, Baltimore, Maryland 21201

ABSTRACT

Ovulationand luteal formation in primates are associated with the sustained synthesis of progesterone. The observed high intrafollicular concentrations of progesterone during the periovulatory interval raise the possibility that this steroid serves as a precursor for mineralocorticoids. The aim of this study was to determine if mineralocorticoids are synthesized by the luteinizing macaque follicle during controlled ovarian stimulation cycles in which follicular fluid and granulosa cell aspirates were obtained before or after an ovulatory hCG bolus. Follicular fluid concentrations of progesterone and 17alpha-hydroxyprogesterone increased within 3 h of an ovulatory hCG bolus. Their respective metabolites, 11-deoxycorticosterone (DOC) and 11-deoxycortisol, were not detectable before an ovulatory stimulus and increased starting at 6 h after hCG, while corticosterone and aldosterone were undetectable. Cortisol was present before and after hCG administration and had increased 2-fold at 24 h after an ovulatory stimulus. The expression of 21-hydroxylase (CYP21A2) mRNA increased within 3 h of hCG administration, while 11beta-hydroxylase-1 (CYP11B1) and 11beta-hydroxylase-2 (CYP11B2) mRNAs were not detectable. 11beta-Hydroxysteroid dehydrogenase-1 (HSD11B1) mRNA had increased at 12 h after hCG administration, and 11beta-hydroxysteroid dehydrogenase-2 (HSD11B2) had decreased by 3 h after hCG administration. Mineralocorticoid receptor mRNA levels did not change following hCG administration, while glucocorticoid receptor mRNA levels increased in response to an ovulatory stimulus.Treatment of granulosa cells with the mineralocorticoid receptor antagonist spironolactone blocked hCG-induced progesterone synthesis in vitro. These data indicate that macaque granulosa cells can synthesize mineralocorticoids in response to an ovulatory stimulus and that the mineralocorticoid receptor plays a key role in steroid synthesis associated with luteinization of macaque granulosa cells.

granulosa cells, luteinization, macaque, mineralocorticoid, ovary, ovulation, steroid hormones, steroidogenesis

¹ Supported in part by grants HD047964 (K.N.F.), RR13439 (C.A.V.), HD043358 (C.L.C.), and RR00169 (CNPRC) from the National Institutes of Health and by a UNCF/Merck fellowship (K.N.F.).

² Correspondence: Charles L. Chaffin, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11–011, 655 W. Baltimore St., Baltimore, MD 21201. FAX: 410 706 5747; cchaffin{at}upi.umaryland.edu

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