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The Androgen-Conjugating Uridine Diphosphoglucuronosyltransferase-2B Enzymes Are Differentially Expressed Temporally and Spatially in the Monkey Follicle throughout the Menstrual Cycle1
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 huma...
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Published in: | Endocrinology (Philadelphia) 2001-06, Vol.142 (6), p.2499-2507 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0013-7227 1945-7170 |
DOI: | 10.1210/endo.142.6.8040 |