H. Wang et al., Effect of adrenal and ovarian androgens on type 4 follicles unresponsive to FSH in immature mice, ENDOCRINOL, 142(11), 2001, pp. 4930-4936
The present study investigates the physiological significance of dehydroepi
androsterone, dehydroepiandrosterone sulfate, T, androstenedione (Delta (4)
), dihydrotestosterone (DHT), estrone (E1), and E2 on recombinant human FSH
- (rhFSH) resistant type 4 follicles obtained from immature mice. Type 4 fo
llicles of a diameter of 100-120 mum with one or two granulosa cell layers
around the oocyte and an intact basal lamina with theca cells were isolated
from the ovaries of 11-d-old BDF-1 mice and cultured with medium alone (co
ntrol) or with dehydroepiandrosterone, dehydroepiandrosterone sulfate, T, D
elta (4), DHT, E1, or E2 at concentrations ranging from 1 X 10(-11) to 1 X
10(-7) m for 4 d. We examined the mean diameters of type 4 follicles, level
s of immunoreactive (IR)-inhibin, and E2 and progesterone in the culture me
dia on day 4. In addition, we evaluated follicular cell proliferation by im
munofluorescence staining with 5-bromo-2'-deoxyuridine. All tested androgen
s significantly increased the diameter of type 4 follicles in a dose-depend
ent manner without the production of IR-inhibin and E2. The nuclei of granu
losa cells in type 4 follicles cultured with all tested androgens exhibited
intense 5-bromo-2'-deoxyuridine-positive staining, compared with those of
controls. In contrast, neither El nor E2 had any stimulatory effects. The s
timulatory effects of T, Delta (4), or DHT were inhibited by an AR antagoni
st in a dose-related fashion but not by an aromatase inhibitor. Furthermore
, all tested androgens had a synergistic effect with rhFSH on follicular gr
owth and the production of IR-inhibin and E2. These results demonstrated th
at neither adrenal nor ovarian androgens are arteriogenic but that they sti
mulate type 4 follicles unresponsive to rhFSH and augment the responsivenes
s of these follicles to rhFSH.