Ka. Vendola et al., ANDROGENS STIMULATE EARLY STAGES OF FOLLICULAR-GROWTH IN THE PRIMATE OVARY, The Journal of clinical investigation, 101(12), 1998, pp. 2622-2629
The concept that androgens are atretogenic, derived from murine ovary
studies, is difficult to reconcile with the fact that hyperandrogenic
women have more developing follicles than normal-cycling women, To eva
luate androgen's effects on primate follicular growth and survival, no
rmal-cycling rhesus monkeys were treated with placebo-, testosterone-(
T), or dihydrotestosterone-sustained release implants, and ovaries wer
e taken for histological analysis after 3-10 d of treatment, Growing p
reantral and small antral follicles up to 1 mm in diameter were signif
icantly and progressively increased in number and thecal layer thickne
ss in T-treated monkeys from 3-10 d. Granulosa and thecal cell prolife
ration, as determined by immunodetection of the Ki67 antigen, were sig
nificantly increased in these follicles, Preovulatory follicles (> 1 m
m), however, were not increased in number in androgen-treated animals,
Follicular atresia was not increased and there were actually signific
antly fewer apoptotic granulosa cells in the T-treated groups. Dihydro
testosterone treatment had identical effects, indicating that these gr
owth-promoting actions are mediated by the androgen receptor. These fi
ndings show that, over the short term at least, androgens are not atre
togenic and actually enhance follicular growth and survival in the pri
mate. These new data provide a plausible explanation for the pathogene
sis of ''polycystic'' ovaries in hyperandrogenism.