Human Physiology, 14th edition (2016)

Reproduction 731

(proliferation) of the stratum functionale of the endometrium.

In humans and other primates, coiled blood vessels called spiral

arteries develop in the endometrium during this phase. Estradiol

may also stimulate the production of receptor proteins for proges-

terone at this time, in preparation for the next phase of the cycle.

The secretory phase of the endometrium occurs when the

ovary is in its luteal phase. In this phase, increased progesterone

secretion by the corpus luteum stimulates the development of

uterine glands. As a result of the combined actions of estradiol

and progesterone, the endometrium becomes thick, vascular,

and “spongy” in appearance, and the uterine glands become

engorged with glycogen during the phase following ovulation.

However, new follicles start to develop toward the end
of one cycle in preparation for the next. This may be due to a
decreased production of inhibin toward the end of the luteal
phase. Estrogen and progesterone levels also fall during the late
luteal phase (starting about day 22) because the corpus luteum
regresses and stops functioning. In lower mammals, the decline
in corpus luteum function is caused by a hormone called luteoly-
sin, secreted by the uterus. There is evidence that the luteolysin
in humans may be prostaglandin F 2 a (see figs. 2.25 and 11.34),
but the mechanisms of corpus luteum regression in humans is
still incompletely understood. Luteolysis (breakdown of the
corpus luteum) can be prevented by high levels of LH, but LH
levels remain low during the luteal phase as a result of negative
feedback exerted by ovarian steroids. Through its secretion of
estradiol and progesterone, the corpus luteum in a sense causes
its own demise.
With the declining function of the corpus luteum, estrogen
and progesterone fall to very low levels by day 28 of the cycle.
The withdrawal of ovarian steroids causes menstruation and
permits a new cycle of follicle development to progress.

Cyclic Changes in the Endometrium

In addition to a description of the female cycle in terms of ovar-
ian function, the cycle can also be described in terms of the
changes in the endometrium of the uterus. These changes occur
because the development of the endometrium is driven by the
cyclic changes in the secretion of estradiol and progesterone
from the ovaries. Three phases can be identified on the basis
of changes in the endometrium: (1) the proliferative phase;
(2) the secretory phase; and (3) the menstrual phase ( fig. 20.33 ,
bottom ).
The proliferative phase of the endometrium occurs while
the ovary is in its follicular phase. The increasing amounts of
estradiol secreted by the developing follicles stimulate growth

Figure 20.34 A corpus luteum in a human
ovary. This structure is formed from the empty graafian follicle
following ovulation.

Figure 20.35 Endocrine control of the ovarian

cycle. This sequence of events is shown together with the

associated phases of the endometrium during the menstrual cycle.

GnRH

Hypothalamus

Anterior pituitary

Ovaries

FSH and LH

Estradiol

Increased sensitivity

of follicles to FSH

Growth of follicles

Estradiol

Positive

feedback

Anterior pituitary

Ovaries

LH surge

Ovulation

[Day 14]

Proliferative phase

Secretory phase

Empty follicle

becomes a

corpus luteum

Estradiol; Progesterone

Negative

feedback

Hypothalamus

GnRH

Anterior pituitary

FSH LH

Ovaries

Corpus luteum

regresses

Estradiol; Progesterone

Decreased negative

feedback inhibition

[Day 1]

[Day 28]

Menstrual phase