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Control of development and atresia of ovarian follicles in mammals (rats, hamsters, guinea pigs, primates); effects of
estrogen, follicle-stimulating hormone, and growth factors on the induction of atresia, studied in vivo and on follicle
cells and oocytes in vitro; regulation of estrogen receptor function and fertility by dioxins. Techniques utilized:
laparotomy, laparoscopy, ultrasonography, cell culture, histology/histochemistry of fixed and frozen sections,
fluorescence microscopy, autoradiography, radioimmunoassay, radioreceptor assay, radio-chemistry, enzyme
assays, image analysis, molecular techniques.
In a typical human menstrual cycle, one ovarian follicle (containing a healthy egg cell) (Figure) from a cohort of a
dozen or so goes on to ovulate, relegating the others to degeneration, or atresia by apoptosis. The primary focus of
our laboratory is the elucidation of those factors involved in the regulation of ovarian follicle development
(folliculogenesis), atresia, and ovulation in mammals. We are particularly intrigued in the role played by estrogen in
this process. We have previously shown that subcutaneous administration of estrogen via capsules induces atresia
of the preovulatory or dominant follicle in rhesus monkeys in vivo, and inhibits steroid synthesis by components of
the follicle in vitro, operating at various enzymatic levels. Some of this inhibitory effect is mediated at the level of the
hypothalamus and pituitary of the brain, and some directly at the level of the ovary. This biomedical model strongly
suggests that it is estrogen from the dominant follicle that causes surrounding follicles to die. The exact
mechanism(s) and locus (loci) of the effect (operant in contraceptive pills), remains elusive. We believe that there is
a complicated network of factors involved in overall regulation of folliculogenesis, including steroids, growth factors
(such as nerve growth factor), cytokines, peptide hormones, xenobiotics (e.g., dioxins) and angiogenic factors, such
as angiotensin II.
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