The Androgen-Conjugating Uridine Diphosphoglucuronosyltransferase-2B Enzymes Are Differentially Expressed Temporally and Spatially in the Monkey Follicle throughout the Menstrual Cycle

Abstract UDP-glucuronosyltransferase (UGT) enzymes enhance the polarity of steroid hormones by catalyzing their conjugation with the sugar group from UDP-glucuronic acid. Previous results have shown that the monkey is a suitable animal model to study steroid glucuronidation in steroid target tissues. In humans, as in the monkey, the main androgen metabolites found in the circulation are 5α-androstane-3α,17β-diol-glucuronide and androsterone glucuronide, and high levels of androsterone glucuronide were also measured in human follicular fluid. Ovarian androgens play a significant role as precursors for estrogens and may modulate the recruitment and growth of follicles. To analyze the expression pattern of UGT2B enzymes involved in androgen metabolism throughout the menstrual cycle, cynomolgus monkey ovaries were collected during the mid and late follicular and luteal phases. Microsomal proteins and total RNA were analyzed for UGT2B expression in the whole ovary. Western blot and specific RT-PCR analyses demonstrated no significant changes in the expression of UGT2B protein or transcripts during the menstrual cycle. Immunocytochemistry analysis showed that UGT2B proteins are expressed in the cytoplasm of thecal and granulosa cells of growing follicles. Interestingly, the thecal cells of secondary follicles and of corpus luteum were extensively stained, whereas luteal granulosa cells were not labeled. These results suggest an important regulation of cell type-specific UGT2B expression during follicular development. Previous results demonstrated similar changes in the expression of the androgen receptor. The colocalization of the androgen receptor and UGT2B enzymes in the same cell types of the ovary provide evidence for a potential role of glucuronidation as a modulator of the intracellular androgen response during follicular development.