Reproduction
621
The reason is that, at this point in the cycle, granulosa cells
have FSH receptors but no LH receptors, and theca cells have
just the reverse. FSH stimulates the granulosa cells to multi-
ply and produce estrogen, and it also stimulates enlargement
of the antrum. Some of the estrogen produced diffuses into
the blood and maintains a relatively stable plasma concentra-
tion
3
. Estrogen also functions as a paracrine/autocrine agent
within the follicle, where, along with FSH and growth factors,
it stimulates the proliferation of granulosa cells, which further
increases estrogen production.
The granulosa cells, however, require help to produce
estrogen because they are defi cient in the enzymes required
to produce the androgen precursors of estrogen (Chapter 11).
The granulosa cells are aided by the theca cells. As shown in
Figure
17–19
, LH acts upon the theca cells, stimulating them
not only to proliferate but also to synthesize androgens. The
androgens diffuse into the granulosa cells and are converted
to estrogen by aromatase. Thus, the secretion of estrogen by
the granulosa cells requires the interplay of both types of fol-
licle cells and both pituitary gonadotropins.
At this point, it is worthwhile to emphasize the similari-
ties that the two types of follicle cells bear to cells of the testes
during this period of the cycle: the granulosa cell is similar
to the Sertoli cell in that it controls the microenvironment in
which the germ cell develops and matures, and it is stimulated
by both FSH and the major gonadal sex hormone. The theca
cell is similar to the Leydig cell in that it produces mainly
androgens and is stimulated to do so by LH.
By the beginning of the second week, one follicle has
become dominant (number
4
in Figure 17–18), and the other
developing follicles degenerate. The reason for this is that, as
shown in Figure 17–18, the plasma concentration of FSH, a
crucial factor necessary for the survival of the follicle cells,
begins to decrease, and there is no longer enough FSH to
prevent atresia. But why, then, does the dominant follicle sur-
vive? There are several reasons why this follicle, having gained
a head start, is able to keep going. First, its granulosa cells
have achieved a greater sensitivity to FSH because of increased
numbers of FSH receptors. Second, its granulosa cells now
begin to be stimulated not only by FSH but by LH as well. We
emphasized in the previous section that, during the fi rst week
or so of the follicular phase, LH acts only on the theca cells.
As the dominant follicle matures, this situation changes, and
LH receptors, induced by FSH, also begin to appear in large
numbers on the granulosa cells. The increase in local estrogen
within the follicle results from these factors.
The dominant follicle now starts to secrete enough estro-
gen that the plasma concentration of this steroid begins to
increase
5
. We can now also explain why plasma FSH starts to
decrease at this time. Estrogen, at these still relatively low concen-
trations, is exerting a
negative feedback
inhibition on the secre-
tion of gonadotropins (Table 17–4 and
Figure 17–20
). A major
site of estrogen action is the anterior pituitary, where it reduces
the amount of FSH and LH secreted in response to any given
amount of GnRH. Estrogen probably also acts on the hypothal-
amus to decrease the amplitude of GnRH pulses and, hence, the
total amount of GnRH secreted over any time period.
Therefore, as expected from this negative feedback, the
plasma concentration of FSH (and LH, to a lesser extent)
begins to decrease as a result of the increasing level of estro-
gen as the follicular phase continues (
6
in Figure 17–18). One
reason that FSH decreases more than LH is that the granulosa
cells also secrete inhibin, which, as in the male, inhibits mainly
the secretion of FSH (see Figure 17–20).
LH Surge and Ovulation
The inhibitory effect of estrogen on gonadotropin secretion
occurs when plasma estrogen concentration is relatively low,
as during the early and middle follicular phases. In contrast,
Table 17–4
Summary of Major Feedback Effects
of Estrogen, Progesterone, and Inhibin
1.
Estrogen,
in
low plasma concentrations,
causes the
anterior pituitary to secrete less FSH and LH in response to
GnRH and also may inhibit the hypothalamic neurons that
secrete GnRH.
Result:
Negative feedback inhibition of FSH and LH
secretion during the early and middle follicular phase.
2.
Inhibin
acts on the pituitary to inhibit the secretion of FSH.
Result:
Negative feedback inhibition of FSH secretion
throughout the cycle.
3.
Estrogen, when increasing dramatically,
causes anterior
pituitary cells to secrete more LH and FSH in response
to GnRH. Estrogen can also stimulate the hypothalamic
neurons that secrete GnRH.
Result:
Positive feedback stimulation of the LH surge,
which triggers ovulation.
4. High plasma concentrations of
progesterone,
in the
presence of estrogen, inhibit the hypothalamic neurons that
secrete GnRH.
Result:
Negative feedback inhibition of FSH and LH
secretion and prevention of LH surges during the luteal
phase and pregnancy.
Ovarian follicle
LH
FSH
Granulosa cells
Convert androgens
to estrogen
Granulosa cells
Convert androgens
to estrogen
(Diffusion)
Theca cells
Synthesize
androgens
Theca cells
Synthesize
androgens
Figure 17–19
Control of estrogen synthesis during the early and middle
follicular phases. (The major androgen secreted by the theca cells is
androstenedione.) Androgen diffusing from theca to granulosa cell
passes through the basement membrane (not shown).
previous page 649 Vander's Human Physiology The Mechanisms of Body Function read online next page 651 Vander's Human Physiology The Mechanisms of Body Function read online Home Toggle text on/off