F I G U R E 3 4 - 4
Hormonal and physiological changes during the menstrual cycle. BBT, Basal body temperature.
to accumulate fluid and leads to formation of an antrum.
Although the intrafollicular concentration of estradiol is
sufficient to stimulate proliferation of granulosa, it is not
high enough to enter the general circulation. For this
reason, the level of circulating estradiol does not increase
during the first half of the follicular phase (Figure 34-4),
and thus the release of LH and FSH is not inhibited but
remains at a fairly constant level.
In the antral stage of follicular growth, production of
estradiol by granulosa cells increases owing to acquisi-
tion of LH receptors by the granulosa cells. Induction of
LH receptors is brought about by the combined effects of
FSH and estradiol and enables the granulosa cells to begin
producing estradiol from pregnenolone. Thus, the forma-
tion of estradiol by aromatization of androgens derived
from the theca interna is augmented by estradiol synthe-
The increased estradiol pool causes marked
acceleration in follicle growth and spillage of estradiol into
the general circulation. Consequently, a relatively rapid in-
crease in circulating estradiol level is seen during the last
days of the follicular phase, which exerts an ini-
tial negative feedback on release of FSH (Figure 34-4).
This rise in estradiol level is a critical cue for the neuroen-
docrine system because it indicates that the ovarian follicle
is ready for ovulation. This message is in the form of an
approximately threefold increase in estradiol level, which
stimulates the release of a large surge of LH and FSH. In
contrast to the negative feedback effect that estradiol nor-
mally exerts on the release of gonadotropins, the very high
levels of estradiol presented over 2-3 days exert a positive
feedback effect. Two mechanisms may operate in this pos-
itive feedback: High levels of estradiol for 2 or 3 days may
increase the sensitivity of the pituitary to GnRH or increase
the release of GnRH from the hypothalamus (or both).